Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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TITLE OF THE INVENTION
ALPHA-CONOTOXIN PEPTIDES
This invention was made with Government support under Grant No. P01 GM48677
awarded
by the National Institute of General Medical Sciences, National Institutes of
Health, Bethesda,
Maryland. The United States Government has certain rights in the invention.
BACKGROUND OF THE INVENTION
The invention relates to relatively short peptides (termed a-conotoxins
herein), about 10-30
residues in length, which are naturally available in minute amounts in the
venom of the cone snails
or analogous to the naturally available peptides, and which preferably include
two disulfide bonds.
The publications and other materials used herein to illuminate the background
of the
invention, and in particular, cases to provide additional details respecting
the practice,
and for convenience are referenced in the following text by author and
date and are listed alphabetically by author in the appended bibliography.
The predatory cone snails (Conus) have developed a unique biological strategy.
Their
venom contains relatively small peptides that are targeted to various
neuromuscular receptors and
may be equivalent in their pharmacological diversity to the alkaloids of
plants or secondary
metabolites of microorganisms. Many of these peptides are among the smallest
nucleic acid-
encoded translation products having defined conformations, and as such, they
are somewhat
unusual. Peptides in this size range normally equilibrate among many
conformations. Proteins
having a fixed conformation are generally much larger.
The cone snails that produce these peptides are a large genus of venomous
gastropods
comprising approximately 500 species. All cone snail species are predators
that inject venom to
capture prey, and the spectrum of animals that the genus as a whole can
envenomate is broad. A
wide variety of hunting strategies are used, however, every Conus species uses
fundamentally the
same basic pattern of envenomation.
Several peptides isolated from Conus venoms have been characterized. These
include the
a-, 4- and c,>-conotoxins which target nicotinic acetylcholine receptors,
muscle sodium channels,
CA 02361534 2007-04-18
2
and neuronal calcium channels, respectively (Olivera et al., 1985).
Conopressins, which are
vasopressin analogs, have also been identified (Cruz et al., 1987). In
addition, peptides
named conantokins have been isolated from Conus geographus and Conus tulipa
(Mena et
al., 1990; Haack et al., 1990).
The a-conotoxins are small peptides highly specific for neuromuscular junction
nicotinic acetylcholine receptors (Gray et al., 1981; Marshall and Harvey,
1990; Blount et al.,
1992; Jacobsen et al., 1997) or highly specific for neuronal nicotinic
acetylcholine receptors
(Fainzilber et al., 1994; Johnson et al., 1995; Cartier et al., 1996; Luo et
al., 1998). The a-
conotoxins with specificity for neuromuscular junction nicotinic acetylcholine
receptors are
used as neuromuscular blocking agents for use in conjunction with surgery, as
disclosed in U.
S. Patent No. 6,268,473, filed 21 January 2000 (Attorney Docket No. 2314-178.
A) and
international patent application publication no. Wo 00/43409, filed 21 January
2000
(Attorney Docket No. 2314-138.PCT). Additional uses for a-conotoxins are
described in
U.S. Patent Nos. 4,447,356 (Olivera et al., 1984); 5,432,155; 5,514,774.
Additional uses for a-conotoxins are described in L.S. Patent 6,265,541, filed
22
December 1998. In this application, a-conotoxins with specificity for neuronal
nicotinic
acetylcholine receptors are used for treating disorders regulated at neuronal
nicotinic
acetylcholine receptors. Such disorders include, but are not limited to,
cardiovascular
disorders, gastric motility disorders, urinary incontinence, nicotine
addiction, mood disorders
(such as bipolar disorder, unipolar depression, dysthymia and seasonal
effective disorder) and
small cell lung carcinoma, as well as the localization of small cell lung
carcinoma.
It is desired to provide additional a -conotoxin peptides having uses as
described
herein.
SUMMARY OF THE INVENTION
The invention relates to relatively short peptides (termed a-conotoxins
herein),
about 10-30 residues in length, which are naturally available in minute
amounts in the venom
of the cone snails or analogous to the naturally available peptides, and which
preferably
include two disulfide bonds.
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2a
More specifically, the present invention is directed to a-conotoxin peptides
having
the general formula I:
Xaal-Xaa2-Xaa3-Xaa4-Xaa5-Cys-Cys-Xaa6-Xaa7-Xaa8-Xaa9-Cys-Xaalo-Xaal i-
Xaal2-Cys-Xaa13 (SEQ ID NO1:), wherein Xaal, is des-Xaal, Ile, Leu or Val;
Xaa2 is des-
Xaa2, Ala or Gly; Xaa3 is des-Xaa3, Gly, Trp (D or L), neo-Trp, halo-Trp or
any unnatural
aromatic amino acid; Xaa4 is des-
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3
Xaa4, Asp, Phe, Gly, Ala, Glu,y-carboxy-Glu (Gla) or any unnatural aromatic
amino acid; Xaa5 is
Glu, Gla, Asp, Ala, Thr, Ser, Gly, Ile, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-
Tyr, O-sulpho-Tyr, 0-
phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa6 is
Ser, Thr, Arg,
ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-
Lys or any
unnatural basic amino acid; Xaa7 is Asp, Glu, Gla, Arg, ornithine,
homoarginine, Lys, N-methyl-
Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid;
Xaa8 is Ser, Thr,
Asn, Ala, Gly, His, halo-His, Pro or hydroxy-Pro; Xaa9 is Thr, Ser, Ala, Asp,
Asn, Pro, hydroxy-
Pro, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-
trimethyl-Lys
or any unnatural basic amino acid; Xaa10 is Gly, Ser, Thr, Ala, Asn, Arg,
ornithine, homoarginine,
Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural
basic amino acid;
Xaaõ is Gln, Leu, His, halo-His, Trp (D or L), halo-Trp, neo-Trp, Tyr, nor-
Tyr, mono-halo-Tyr, di-
halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr, nitro-Tyr, Arg, ornithine,
homoarginine, Lys, N-methyl-
Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid or
any unnatural
aromatic amino acid; Xaa12 is Asn, His, halo-His, Ile, Leu, Val, Gln, Arg,
ornithine, homoarginine,
Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural
basic amino acid;
Xaa13 is des-Xaa,3, Val, Ile, Leu, Arg, ornithine, homoarginine, Lys, N-methyl-
Lys, N,N-dimethyl-
Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid. The C-terminus may
contain a free
carboxyl group or an amide group. The halo is chlorine, bromine or iodine,
preferably iodine for
Tyr and His and preferably bromine for Tip. The Cys residues may be in D or L
configuration and
may optionally be substituted with homocysteine (D or L). The Tyr residues may
be substituted
with the 3-hydroxyl or 2-hydroxyl isomers and corresponding O-sulpho- and O-
phospho-
derivatives. The acidic amino acid residues may be substituted with any
synthetic acidic bioisoteric
amino acid surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
More specifically, the present invention is directed to a-conotoxin peptides
having the
general formula II:
Xaa, -Xaa2-Xaa3-Xaa4-Cys-Cys-Xaa5-Xaa6-Xaa7-Xaa8-Cys-Xaa9-Xaa, o-Xaa, , -Xaa,
2-Xaa, 3-
Xaa14-Cys-Xaa15-Xaa16-Xaa17 (SEQ ID NO:2), wherein Xaa, is des-Xaa,, Asp, Glu
or y-carboxy-Glu
(Gla); Xaa, is des-Xaa2, Gln, Ala, Asp, Glu, Gla; Xaa3 is des-Xaa3, Gly, Ala,
Asp, Glu, Gla, Pro or
hydroxy-Pro; Xaa4 is des-Xaa4, Gly, Glu, Gla, Gln, Asp, Asn, Pro or hydroxy-
Pro; Xaa5 is Ser, Thr,
Gly, Glu, Gla, Asn, Trp (D or L), neo-Trp, halo-Trp, Arg, ornithine,
homoarginine, Lys, N-methyl-
Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid,
Tyr, nor-Tyr, mono-
halo-Tyr, di-halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr, nitro-Tyr or any unnatural
hydroxy containing
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4
amino acid; Xaa6 is Asp, Asn, His, halo-His, Thr, Ser, Tyr, nor-Tyr, mono-halo-
Tyr, di-halo-Tyr,
O-sulpho-Tyr, 0-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing
amino acid; Xaa7 is
Pro or hydroxy-Pro; Xaa8 is Ala, Ser, Thr, Asp, Val, Ile, Pro, hydroxy-Pro,
Tyr, nor-Tyr, mono-halo-
Tyr, di-halo-Tyr, O-sulpho-Tyr, 0-phospho-Tyr, nitro-Tyr or any unnatural
hydroxy containing
amino acid; Xaag is Gly, Ile, Leu, Val, Ala, Thr, Ser, Pro, hydroxy-Pro, Phe,
Tip (D or L), neo-Trp,
halo-Trp, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys,
N,N,N-trimethyl-
Lys, any unnatural basic amino acid or any unnatural aromatic amino acid;
Xaa10 is Ala, Asn, Phe,
Pro, hydroxy-Pro, Glu, Gla, Gln, His, halo-His, Val, Ser, Thr, Arg, ornithine,
homoarginine, Lys,
N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic
amino acid; Xaaõ
is Thr, Ser, His, halo-His, Leu, Ile, Val, Asn, Met, Pro, hydroxy-Pro, Arg,
ornithine, homoarginine,
Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic
amino acid, Tyr,
nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, 0-phospho-Tyr, nitro-Tyr or
any unnatural
hydroxy containing amino acid; Xaa12 is Asn, Pro, hydroxy-Pro, Gln, Ser, Thr,
Arg, ornithine,
homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys N,N,N-trimethyl-Lys, any
unnatural basic
amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, 0-phospho-
Tyr, nitro-Tyr or
any unnatural hydroxy containing amino acid; Xaa13 is des-Xaa13, Gly, Thr,
Ser, Pro, hydroxy-Pro,
Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, 0-phospho-Tyr, nitro-
Tyr or any
unnatural hydroxy containing amino acid; Xaa14 is des-Xaa14, Ile, Val, Asp,
Leu, Phe, Arg, ornithine,
homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, any
unnatural basic
amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, 0-phospho-
Tyr, nitro-Tyr or
any unnatural hydroxy containing amino acid; and Xaa15 is des-Xaa15, Gly, Ala,
Met, Ser, Thr, Tip
(D or L), neo-Trp, halo-Tip, any unnatural aromatic amino acid, Arg,
ornithine, homoarginine, Lys,
N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic
amino acid; Xaa16
is des-Xaa16, Trp (D or L), neo-Trp, halo-Trp, any unnatural aromatic amino
acid, Arg, ornithine,
homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any
unnatural basic
amino acid; Xaa17 is des-Xaa17, Arg, ornithine, homoarginine, Lys, N-methyl-
Lys, N,N-dimethyl-
Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid. The C-terminus may
contain a free
carboxyl group or an amide group. The halo is preferably bromine, chlorine or
iodine, more
preferably iodine for His or Tyr and bromine for Tip. The Cys residues may be
in D or L
configuration and may optionally be substituted with homocysteine (D or L).
The Tyr residues may
be substituted with the 3-hydroxyl or 2-hydroxyl isomers and corresponding O-
sulpho- and 0-
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phospho-derivatives. The acidic amino acid residues may be substituted with
any synthetic acidic
bioisoteric amino acid surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
More specifically, the present invention is directed to a-conotoxin peptides
having the
general formula III:
5 Xaa,-Xaa2-Xaa3-Xaa4-Xaa5-Cys-Cys-Xaa6-Xaa7-Xaa8-Xaa9-Cys-Xaa10-Xaa11-Xaa,2-
Xaa,3-
Xaa14-Xaa15-Xaa16-Cys-Xaa17-Xaa18-Xaa19-Xaa20-Xaa21-Xaa22-Xaa23-Xaa24 (SEQ ID
NO:3), wherein
Xaa1 is des-Xaa1, Ser or Thr; Xaa2 is des-Xaa2, Asp, Glu, y-carboxy-Glu (Gla),
Asn, Ser or Thr;
Xaa3 is des-Xaa3, Ala, Gly, Asn, Ser, Thr, Pro, hydroxy-Pro, Arg, ornithine,
homoarginine, Lys, N-
methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino
acid; Xaa4 is
des-Xaa4, Ala, Val, Leu, Ile, Gly, Glu, Gla, Gln, Asp, Asn, Phe, Pro, hydroxy-
Pro or any unnatural
aromatic amino acid; Xaa5 is des-Xaa5, Thr, Ser, Asp, Glu, Gla, Gin, Gly, Val,
Asp, Asn, Ala, Pro,
hydroxy-Pro, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-
Lys, N,N,N-
trimethyl-Lys or any unnatural basic amino acid; Xaa6 is Thr, Ser, Asp, Asn,
Met, Val, Ala, Gly,
Leu, Ile, Phe, any unnatural aromatic amino acid, Pro, hydroxy-Pro, Tyr, nor-
Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy
containing amino
acid; Xaa7 is Ile, Leu, Val, Ser, Thr,. Gln, Asn, Asp, Arg, His, halo-His,
Phe, any unnatural aromatic
amino acid, homoarginine, ornithine, Lys, N-methyl-Lys, NN-dimethyl-Lys, N,N,N-
trimethyl-Lys,
any unnatural basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-
sulpho-Tyr, 0-
phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa8 is
Pro, hyroxy-Pro,
Ser, Thr, Ile, Asp, Leu, Val, Gly, Ala, Phe, any unnatural aromatic amino
acid, Arg, ornithine,
homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any
unnatural basic
amino acid; Xaa9 is Val, Ala, Gly, Ile, Leu, Asp, Ser, Thr, Pro, hydroxy-Pro,
Arg, ornithine,
homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any
unnatural basic
amino acid; Xaa10 is His, halo-His, Arg, homoarginine, ornithine, Lys, N-
methyl-Lys, N,N-
dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic amino acid, Asn, Ala,
Ser, Thr, Phe, Ile,
Leu, Gly, Trp (D or L), neo-Trp, halo-Trp, any unnatural aromatic amino acid,
Tyr, nor-Tyr, mono-
halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural
hydroxy containing
amino acid; Xaa11 is Leu, Gln, Val, Ile, Gly, Met, Ala, Lys, N-methyl-Lys, N,N-
dimethyl-Lys,
N,N,N-trimethyl-Lys, Ser, Thr, Arg, homoarginine, ornithine, any unnatural
basic amino acid, Asn,
Glu, Gla, Gln, Phe, Trp (D or L), neo-Trp, halo-Trp or any unnatural aromatic
amino acid; Xaa12 is
Glu, Gla, Gln, Asn, Asp, Pro, hydroxy-Pro, Ser, Gly, Thr, Lys, N-methyl-Lys,
N,N-dimethyl-Lys,
N,N,N-trimethyl-Lys, Arg, homoarginine, ornithine, any unnatural basic amino
acid, Phe, His, halo-
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His, any unnatural aromatic amino acid, Leu, Met, Gly, Ala, Tyr, nor-Tyr, mono-
halo-Tyr, di-halo-
Tyr, O-sulpho-Tyr, 0-phospho-Tyr, nitro-Tyr or any unnatural hydroxy
containing amino acid;
Xaa13 is His, halo-His, Asn, Thr, Ser, Ile, Val, Leu, Phe, any unnatural
aromatic amino acid, Arg,
homoarginine, ornithine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-
Lys, any
unnatural basic amino acid, Tyr, nor-Try, mono-halo-Tyr, di-halo-Tyr, O-sulpho-
Tyr, 0-phospho-
Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa14 is Ser,
Thr, Ala, Gin, Pro,
hydroxy-Pro, Gly, Ile, Leu, Arg, ornithine, homoarginine, Lys, N-methyl-Lys,
N,N-dimethyl-Lys,
N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa15 is Asn, Glu, Gla,
Asp, Gly, His, halo-
His, Ala, Leu, Gln, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-
dimethyl-Lys, N,N,N-
trimethyl-Lys, any unnatural basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-
halo-Tyr, O-sulpho-
Tyr, 0-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid;
Xaa16 is Met, Ile,
Thr, Ser, Val, Leu, Pro, hydroxy-Pro, Phe, any unnatural aromatic amino acid,
Tyr, nor-Tyr, mono-
halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, 0-phospho-Tyr, nitro-Tyr, any unnatural
hydroxy containing
amino acid, Glu, Gla, Ala, His, halo-His, Arg, omithine, homoarginine, Lys, N-
methyl-Lys, N,N-
dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa17 is
des-Xaa17, Gly, Asp,
Asn, Ala, Ile, Leu, Ser, Thr, His, halo-His, Arg, ornithine, homoarginine,
Lys, N-methyl-Lys, N,N-
dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa, 8 is
des-Xaa18, Gly, Glu,
Gla, Gln, Trp (D or L), neo, halo-Trp, any unnatural aromatic amino acid, Arg,
ornithine,
homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any
unnatural basic
amino acid; Xaa19 is des-Xaa19, Ser, Thr, Val, Ile, Ala, Arg, omithine,
homoarginine, Lys, N-methyl-
Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid;
Xaa20 is des-Xaa20,
Val, Asp, His, halo-His, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-
dimethyl-Lys,
N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa21 is des-Xaa,1,
Asn, Pro or hydroxy-
Pro; Xaa22 is des-Xaa22, Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-
dimethyl-Lys,
N,N,N-trimethyl-Lys or any unnatural basic amino acid; Xaa23 is des-Xaa23, Ser
or Thr; Xaa24 is des-
Xaa24, Leu, Ile or Val; with the proviso that (a) Xaa5 is not Gly, when Xaa1
is des-Xaa1, Xaa2 is des-
Xaa2, Xaa3 is des-Xaa3, Xaa4 is des-Xaa4, Xaa6 is Ser, Xaa7 is His, Xaa8 is
Pro, Xaa9 is Ala, Xaa10
is Ser, Xaa11 is Val, Xaa12 is Asn, Xaa13 is Asn, Xaa14 is Pro, Xaa15 is Asp,
Xaa16 is Ile, Xaa17 is des-
Xaa17, Xaa18 is des-Xaa18, Xaa19 is des-Xaa19, Xaa20 is des-Xaa20, Xaa,l is
des-Xaa71, Xaa2, is des-
Xaa22, Xaa23 is des-Xaa23, and Xaa24 is des-Xaa24. The C-terminus may contain
a free carboxyl
group or an amide group. The halo is preferably bromine, chlorine or iodine,
more preferably iodine
for His and Tyr and bromine for Trp. The Cys residues may be in D or L
configuration and may
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7
optionally be substituted with homocysteine (D or L). The Tyr residues may be
substituted with the
3-hydroxyl or 2-hydroxyl isomers and corresponding O-sulpho- and 0-phospho-
derivatives. The
acidic amino acid residues may be substituted with any synthetic acidic
bioisoteric amino acid
surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
The present invention is also directed to novel specific a-conotoxin peptides
of general
formula I having the formulas:
Asp-Xaa,-Cys-Cys-Ser-Asp-Ser-Arg-Cys-Gly-Xaa2-Asn-Cys-Leu (SEQ ID NO:4);
Ala-Cys-Cys-Ser-Asp-Arg-Arg-Cys-Arg-Xaa3-Arg-Cys (SEQ ID NO:5);
Phe-Thr-Cys-Cys-Arg-Arg-Gly-Thr-Cys-Ser-Gln-His-Cys (SEQ ID NO:6);
Asp-Xaa4-Cys-Cys-Arg-Arg-His-Ala-Cys-Thr-Leu-Ile-Cys (SEQ ID NO:7);
Asp-Xaa4-Cys-Cys-Arg-Xaa5-Xaa5-Cys-Thr-Leu-Ile-Cys (SEQ ID NO:8);
Gly-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Arg-Xaa4-Arg-Cys-Arg (SEQ ID NO:9);
Gly-Gly-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ala-Xaa3-Arg-Cys (SEQ ID NO:10);
Ile-Ala-Xaa3-Asp-Ile-Cys-Cys-Ser-Xaa,-Xaa5-Asp-Cys-Asn-His-Xaa2-Cys-Val (SEQ
ID
NO: 11); and
Gly-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Xaa2-His-Gln-Cys (SEQ ID NO:12),
wherein Xaa, is Glu or y-carboxy-Glu (Gla); Xaa2 is Lys, N-methyl-Lys, N,N-
dimethyl-Lys or
N,N,N-trimethyl-Lys; Xaa3 is Trp (D or L), halo-Trp or neo-Trp; Xaa4 is Tyr,
nor-Tyr, mono-halo-
Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr; and Xaa5 is Pro or
hydroxy-Pro; and
the C-terminus contains a carboxyl or amide group. The halo is preferably
bromine, chlorine or
iodine, more preferably iodine for Tyr and bromine for Trp. In addition, the
His residues may be
substituted with halo-His; the Arg residues may be substituted by Lys,
ornithine, homoargine, N-
methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino
acid; the Lys
residues may be substituted by Arg, ornithine, homoargine, N-methyl-Lys, N,N-
dimethyl-Lys,
N,N,N-trimethyl-Lys or any unnatural basic amino acid; the Tyr residues may be
substituted with
any unnatural hydroxy containing amino acid; the Ser residues may be
substituted with Thr; the Thr
residues may be substituted with Ser; and the Phe and Trp residues may be
substituted with any
unnatural aromatic amino acid. The Cys residues may be in D or L configuration
and may
optionally be substituted with homocysteine (D or L). The Tyr residues may be
substituted with the
3-hydroxyl or 2-hydroxyl isomers and corresponding O-sulpho- and 0-phospho-
derivatives. The
acidic amino acid residues may be substituted with any synthetic acidic
bioisoteric amino acid
surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
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8 More specifically, the present invention is directed to the following a-
conotoxin peptides
of general formula I:
Iml.l : SEQ ID NO:4, wherein Xaa, is Glu and Xaa, is Lys;
Iml.2: SEQ ID NO:5, wherein Xaa3 is Trp;
Rgl.2: SEQ ID NO:6;
Rg 1.6: SEQ ID NO:7, wherein Xaa4 is Tyr;
Rgl.6A: SEQ ID NO:8, wherein Xaa4 is Tyr and Xaa5 is Pro;
Rg 1.7: SEQ ID NO:9, wherein Xaa4 is Tyr and Xaa5 is Pro;
Rgl.9: SEQ ID NO:10, wherein Xaa3 is Trp and Xaa5 is Pro;
Rgl.10: SEQ ID NO:11, wherein Xaa, is Glu, Xaa2 is Lys, Xaa3 is Trp and Xaa5
is
Pro; and
Rg1.11: SEQ ID NO:12, wherein Xaa2 is Lys and Xaa5 is Pro.
The C-terminus of Im 1.1, Rg 1.7 an Rg 1.10 preferably contains a free
carboxyl group. The C-
terminus of Iml.2, Rgl.2, Rgl.6, Rg l .6A, Rgl.9 and Rg 1.11 preferably
contains an amide group.
The present invention is further directed to novel specific a-conotoxin
peptides of general
formula II having the formulas:
Cys-Cys-Ser-Asp-Xaa5-Ala-Cys-Xaa2-Gln-Thr-Xaa5-Gly-Cys-Arg (SEQ ID NO: 13);
Cys-Cys-Xaa,-Asn-Xaa5-Ala-Cys-Arg-His-Thr-Gln-Gly-Cys (SEQ ID NO: 14);
Gly-Cys-Cys-Xaa3-His-Xaa5-Ala-Cys-Gly-Arg-His-Xaa4-CYS (SEQ ID NO: 15);
Ala-Xaa5-Cys-Cys-Asn-Asn-Xaa5-Ala-Cys-Val-Xaa2-His-Arg-Cys (SEQ ID NO: 16);
Ala-Xaa5-Gly-Cys-Cys-Asn-Asn-Xaa5-Ala-Cys-Val-Xaa2-His-Arg-Cys (SEQ ID NO:
17);
Xaa5-Xaa5-Cys-Cys-Asn-Asn-Xaa5-Ala-Cys-Val-Xaa2-His-Arg-Cys (SEQ ID NO:18);
Asp-Xaa,-Asn-Cys-Cys-Xaa3-Asn-Xaa5-Ser-Cys-Xaa5-Arg-Xaa5-Arg-Cys-Thr (SEQ ID
NO:19);
Gly-Cys-Cys-Ser-Thr-Xaa5-Xaa5-Cys-Ala-Val-Leu-Xaa4-Cys (SEQ ID NO:20);
Gly-Cys-Cys-Gly-Asn-Xaa5-Asp-Cys-Thr-Ser-His-Ser-Cys (SEQ ID NO:21);
Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ala-His-Asn-Asn-Xaa5-Asp-Cys-Arg (SEQ ID
NO:42);
Gly-Cys-Cys-Xaa4-Asn-Xaa5-Val-Cys-Xaa2-Xaa,-Xaa4-Xaa4-Cys-Xaa3-Xaa, (SEQ ID
NO:154);
Xaa6-Xaa,-Xaa5-Gly-Cys-Cys-Arg-His-Xaa5-Ala-Cys-Gly-Xaa2-Asn-Arg-Cys (SEQ ID
NO:155);
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9
Cys-Cys-Ala-Asp-Xaa5-Asp-Cys-Arg-Phe-Arg-Xaa5-Gly-Cys (SEQ ID NO:156);
Gly-Cys-Cys-Xaa4 Asn-Xaa5-Ser-Cys-Xaa3-Xaa5-Xaaz Thr-Xaa4-Cys-Ser-Xaa3-Xaa2
(SEQ
ID NO:157);
Cys-Cys-Ser-Asn-Xaa5-Thr-Cys-Xaa2-Xaal-Thr-Xaa4-Gly-Cys (SEQ ID NO: 158);
Cys-Cys-Ala-Asn-Xaa5-Ile-Cys-Xaa2-Asn-Thr-Xaa5-Gly-Cys (SEQ ID NO: 159);
Cys-Cys-Asn-Asn-Xaa5-Thr-Cys-Xaa2-Xaa,-Thr-Xaa4-Gly-Cys (SEQ ID NO:160);
Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Xaa2-Xaa,-Thr-Xaa4-Gly-Cys (SEQ ID NO: 161);
Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Xaa5-Cys-Ile-Ala-Ser-Asn-Xaa5-Xaa2-Cys-Gly (SEQ
ID
NO:162);
Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Ser-Ala-Met-Ser-Xaa5-Ile-Cys (SEQ ID NO:
163);
Gly-Cys-Cys-Xaa2-Asn-Xaa5-Xaa4-Cys-Gly-Ala-Ser-Xaa2-Thr-Xaa4-Cys (SEQ ID NO:
164);
Gly-Cys-Cys-Ser-Xaa4-Xaa5-Xaa5-Cys-Phe-Ala-Thr-Asn-Xaa5-Asp-Cys (SEQ ID
NO:165);
Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Xaa5-Cys-Ile-Ala-Asn-Asn-Xaa5-Leu-Cys-Ala (SEQ
ID
NO:166);
Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Xaa5-Cys-Ile-Ala-Asn-Asn-Xaa5-Phe-Cys-Ala (SEQ
ID
NO:167);
Asp-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ser-Gln-Asn-Asn-Xaa5-Asp-Cys-Met (SEQ ID
NO:168); and
Asp-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ala-His-Asn-Asn-Xaa5-Asp-Cys-Arg (SEQ ID
NO:169),
wherein Xaa, is Glu or y-carboxy-Glu (Gla); Xaa2 is Lys, N-methyl-Lys, N,N-
dimethyl-Lys or
N,N,N-trimethyl-Lys; Xaa3 is Trp (D or L), halo-Trp or neo-Trp; Xaa4 is Tyr,
nor-Tyr, mono-halo-
Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr; and Xaa5 is Pro or
hydroxy-Pro; and
the C-terminus contains a carboxyl or amide group. The halo is preferably
bromine, chlorine or
iodine, more preferably iodine for Tyr and bromine for Trp. In addition, the
His residues may be
substituted with halo-His; the Arg residues may be substituted by Lys,
ornithine, homoargine, N-
methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino
acid; the Lys
residues may be substituted by Arg, ornithine, homoargine, N-methyl-Lys, N,N-
dimethyl-Lys,
N,N,N-trimethyl-Lys or any unnatural basic amino acid; the Tyr residues may be
substituted with
any unnatural hydroxy containing amino acid; the Ser residues may be
substituted with Thr; the Thr
residues may be substituted with Ser; and the Phe and Trp residues may be
substituted with any
unnatural aromatic amino acid. The Cys residues may be in D or L configuration
and may
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optionally be substituted with homocysteine (D or L). The Tyr residues may be
substituted with the
3-hydroxyl or 2-hydroxyl isomers and corresponding O-sulpho- and O-phospho-
derivatives. The
acidic amino acid residues may be substituted with any synthetic acidic
bioisoteric amino acid
surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
5 More specifically, the present invention is directed to the following a-
conotoxin peptides
of general formula II:
Snl.l : SEQ ID NO: 13, wherein Xaa2 is Lys and Xaa5 is Pro;
Sn1.2: SEQ ID NO: 14, wherein Xaa, is Glu and Xaa5 is Pro;
Sl1.3: SEQ ID NO: 15, wherein Xaa3 is Trp, Xaa4 is Tyr and Xaa5 is Pro;
10 A1.2: SEQ ID NO:16, wherein Xaa2 is Lys and Xaa5 is Pro;
Bul.l : SEQ ID NO: 17, wherein Xaa2 is Lys and Xaa5 is Pro;
Bul.2: SEQ ID NO:18, wherein Xaa2 is Lys and Xaa5 is Pro;
Bul.3: SEQ ID NO: 19, wherein Xaa, is Glu, Xaa3 is Trp and Xaa5 is Pro;
Bul.4: SEQ ID NO:20, wherein Xaa4 is Tyr and Xaa5 is Pro ;
Cr1.3: SEQ ID NO:21, wherein Xaa5 is Pro;
Di 1.1: SEQ ID NO:42 wherein Xaa5 is Pro;
Msl.7: SEQ ID NO: 154, wherein Xaa2 is Lys, Xaa3 is Trp, Xaa4 is Tyr and Xaa5
is
Pro;
P1.7: SEQ ID NO:155, wherein Xaa, is Glu, Xaa2 is Lys, Xaa5 is Pro and Xaa6 is
Gln;
Msl.2: SEQ ID NO:156, wherein Xaa5 is Pro;
Msl.3: SEQ ID NO: 157, wherein Xaa2 is Lys, Xaa3 is Trp, Xaa4 is Tyr and Xaa5
is
Pro;
Msl.4: SEQ ID NO:158, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa4 is Tyr and Xaa5
is
Pro;
Msl.5: SEQ ID NO:159, wherein Xaa2 is Lys and Xaa5 is Pro;
Msl.8: SEQ ID NO: 160, wherein Xaa1 is Glu, Xaa2 is Lys, Xaa4 is Tyr and Xaa5
is
Pro;
Msl.9: SEQ ID NO:161, wherein Xaa, is Glu, Xaa2 is Lys, Xaa4 is Tyr and Xaa5
is
Pro;
Btl.7: SEQ ID NO:162, wherein Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
Lvl.5: SEQ ID NO:163, wherein Xaa5 is Pro;
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Ms1.10: SEQ ID NO:164, wherein Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
Oml.1: SEQ ID NO:165, wherein Xaa4 is Tyr and Xaa5 is Pro;
R1.6: SEQ ID NO:166, wherein Xaa4 is Tyr and Xaa5 is Pro;
R1.7: SEQ ID NO:167, wherein Xaa4 is Tyr and Xaa5 is Pro;
Vrl.1: SEQ ID NO: 168, wherein Xaa5 is Pro; and
Vrl.2: SEQ ID NO:169, wherein Xaa5 is Pro.
The C-terminus preferably contains a carboxyl group for the peptides Snl.l,
Snl.2, Cr1.3, Dil.l,
Msl.2, Msl.4, Msl.5, Msl.8, Msl.9, Vrl.1 and Vrl.2. The C-terminus of the
other peptides
preferably contains an amide group.
The present invention is also directed to novel specific a-conotoxin peptides
of general
formula III having the formulas:
Gly-Cys-Cys-Ser-Asn-Xaa5-V al-Cys-His-L eu-Xaa, -His-Ser-Asn-Met-Cys (SEQ ID
NO:22);
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Arg-Gln-Asn-Asn-Ala-Xaa,-Xaa4-Cys-Arg (SEQ ID
NO:23);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa,-Ile-Cys-Arg
(SEQ
ID NO:24);
Xaa5-Xaa,-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa,-Ile-Cys-Arg
(SEQ
ID NO:25);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa,-Ile-Cys-Asp
(SEQ
ID NO:26);
Xaa5-Arg-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa,-Ile-Cys-Arg
(SEQ
ID NO:27);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Gly-Ile-Cys-Arg
(SEQ
ID NO:28);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa,-Thr-Cys-Arg
(SEQ
ID NO:29);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa,-Val-Cys-Arg
(SEQ
ID NO:30);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Ile-Asp-His-Xaa5-Xaa,-Ile-Cys-Arg
(SEQ
ID NO:31);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-V al-Asp-His-Xaa5-Xaa, -Ile-Cys-Arg-
Arg-
Arg-Arg (SEQ ID NO:32);
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Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Val-Asn-His-Xaa5-Xaa,-Leu-Cys (SEQ ID
NO:33);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Asn-His-Xaa5-Xaa,-Leu-Cys (SEQ
IDNO:34);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa,-Ile-Cys (SEQ
IDNO:35);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Xaa2-Thr-Gln-Xaa, -Xaa5-Cys-Arg-Xaa,-
Ser
(SEQ ID NO:36);
Xaa5-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Xaa5-Xaa,-Phe-Cys-Arg-Gln
(SEQ
ID NO:37);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Xaa5-Xaa,-Phe-Cys-Arg-Gln
(SEQ
ID NO:38);
Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Ala-Met-Asn-Asn-Xaa5-Asp-Xaa4-Cys (SEQ ID
NO:39);
Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Phe-Leu-Asn-Asn-Xaa5-Asp-Xaa4-Cys (SEQ ID
NO:40);
Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ile-Ala-Xaa2-Asn-Xaa5-His-Met-Cys-Gly (SEQ
ID
NO:41);
Gly-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Val-Cys-Arg-Gln (SEQ
ID NO:43);
Gly-Cys-Cys-Ser-Arg-Xaa5-Ala-Cys-Ile-Ala-Asn-Asn-Xaa5-Asp-Leu-Cys (SEQ
IDNO:44);
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Val-Xaa,-His-Xaa5-Xaa,-Leu-Cys-Arg-Arg-
Arg-
Arg (SEQ ID NO:45);
Gly-Gly-Cys-Cys-Ser-Phe-Xaa5-Ala-Cys-Arg-Xaa2-Xaa5-Arg-Xaa5-Xaa,-Met-Cys-
Gly(SEQ
ID NO:46);
Xaa5-Xaa,-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Ser-Ser-His-Xaa5-Xaa, -Leu-Cys-
Gly(SEQ
ID NO:47);
Xaa5-Gln-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-V al-Gly-His-Xaa5-Xaa, -Leu-Cys-
Gly(SEQ
ID NO:48);
Xaa6-Val-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Val-Gly-His-Xaa5-Xaa,-Ile-Cys-Gly
(SEQ
ID NO:49);
Gly-Cys-Cys-Ser-Arg-Xaa5-Xaa5-Cys-Ile-Ala-Asn-Asn-Xaa5-Asp-Leu-Cys (SEQ ID
NO:50);
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Xaa5-Gln-Cys-Cys-Ser-His-Leu-Ala-Cys-Asn-Val-Asp-His-XaaS-Xaa,-Ile-Cys-Arg
(SEQ
ID NO:51);
Gly-Cys-Cys-Ser-Xaa4-Phe-Asp-Cys-Arg-Met-Met-Phe-XaaS-Xaa,-Met-Cys-Gly-Xaa3-
Arg
(SEQ ID NO:52);
Gly-Gly-Cys-Cys-Ser-Phe-Ala-Ala-Cys-Arg-Xaa2-Xaa4-Arg-XaaS-Xaa,-Met-Cys-
Gly(SEQ
ID NO:53);
Gly-Gly-Cys-Cys-Phe-His-XaaS-Val-Cys-Xaa4-Ile-Asn-Leu-Leu-Xaa, -Met-Cys-Arg-
Gln-
Arg (SEQ ID NO:54);
Ser-Ala-Thr-Cys-Cys-Asn-Xaa4-XaaS-XaaS-Cys-Xaa4-Xaa, -Thr-Xaa4-XaaS-Xaa, -Ser-
Cys-
Leu (SEQ ID NO:55);
Ala-Cys-Cys-Ala-Xaa4-Xaa5 Xaa5-Cys-Phe-Xaa,-Ala-Xaa4-XaaS-Xaa,-Arg-Cys-Leu
(SEQ
ID NO: 56);
Asn-Ala-Xaa, -Cys-Cys-Xaa4-Xaa4-Xaa5-Xaa5-Cys-Xaa4-Xaa, -Al a-Xaa4-Xaa5-Xaa, -
Ile-Cys-
Leu (SEQ ID NO:57);
Xaa,-Cys-Cys-Thr-Asn-Xaa5-Val-Cys-His-Ala-Xaa,-His-Gln-Xaa,-Leu-Cys-Ala-Arg-
Arg-
Arg (SEQ ID NO:170);
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa,-His-Ser-Asn-Leu-Cys (SEQ ID
NO: 171);
Xaa,-Cys-Cys-Thr-Asn-Xaa5-Val-Cys-His-Val-Xaa,-His-Gln-Xaa, -Leu-Cys-Ala-Arg-
Arg-
Arg (SEQ ID NO:172);
Xaa6-Xaal-Cys-Cys-Ser-Xaa4-Xaa5-Ala-Cys-Asn-Leu-Asp-His-Xaa5-Xaa,-Leu-Cys (SEQ
ID NO:173);
Xaa5-Xaa, -Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Ser-Thr-His-Xaa5-Xaa,-Leu-Cys-
Gly(SEQ
ID NO:174);
Leu-Asn-Cys-Cys-Met-Ile-Xaa5-Xaa5-Cys-Xaa3-Xaa,-Xaa,-Xaa4-Gly-Asp-Arg-Cys-Ser-
Xaa,-Val-Arg (SEQ ID NO:175);
Ala-Phe-Gly-Cys-Cys-Asp-Leu-Ile-Xaa5-Cys-Leu-Xaa, -Arg-Xaa4-Gly-Asn-Arg-Cys-
Asn-
Xaa,-Val-His (SEQ ID NO:176);
Leu-Gly-Cys-Cys-Asn-V al-Thr-Xaa5-Cys-Xaa3-Xaa, -Xaa2-Xaa4-Gly-Asp-Xaa2-Cys-
Asn-
Xaa,-Val-Arg (SEQ ID NO:177);
Asp-Xaa,-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Arg-V al-Asn-Asn-Xaa5-His-V al-Cys-Arg-
Arg-
Arg (SEQ ID NO:178);
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Leu-Asn-Cys-Cys-S er-I le-Xaa5-Gly-Cys-Xaa3-Asn-Xaa, -Xaa4-Xaa2-Asp-Arg-Cys-
Ser-Xaa2-
Val-Arg (SEQ ID NO:179);
Gly-Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Xaa4-Phe-Asn-Asn-Xaa5-Gln-Met-Cys-Arg
(SEQ
ID NO:180);
Gly-Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Asn-Leu-Asn-Asn-Xaa5-Gln-Met-Cys-Arg (SEQ
ID NO:181);
Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Xaa4-Ala-Asn-Asn-Gln-Ala-Xaa4-Cys-Asn (SEQ
ID
NO:182);
Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Thr-His-Xaa5-Xaa,-Leu-Cys (SEQ ID
NO:183);
Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Ala-Cys-Ser-Val-Xaa,-His-Gln-Asp-Leu-Cys-Asp
(SEQ
ID NO:184);
V al-Ser-Cys-Cys-V al-V al-Arg-Xaa5-Cys-Xaa3-I le-Arg-Xaa4-Gln-Xaa, -Xaa, -Cys-
Leu-Xaa, -
Ala-Asp-Xaa5-Arg-Thr-Leu (SEQ ID NO: 185);
Xaa6-Asn-Cys-Cys-Ser-Ile-Xaa5-Gly-Cys-Xaa3-Xaa,-Xaa,-Xaa4-Gly-Asp-Xaa2-Cys-Ser-
Xaa,-Val-Arg (SEQ ID NO:186);
G1y-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa,-His-Xaa5-Asn-Ala-Cys (SEQ ID
NO:187);
Gly-Cys-Cys-Ser-Asn-Xaa5-Ile-Cys-Xaa4-Phe-Asn-Asn-Xaa5-Arg-Ile-Cys-Arg (SEQ ID
NO:188);
Xaa,-Cys-Cys-Ser-Gln-Xaa5-Xaa5-Cys-Arg-Xaa3-Xaa2-His-Xaa5-Xaa,-Leu-Cys-Ser
(SEQ
ID NO:189);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Gln-His-Ile-Cys (SEQ ID NO:
190);
Gly-Cys-Cys-Ala-Val-Xaa5-Ser-Cys-Arg-Leu-Arg-Asn-Xaa5-Asp-Leu-Cys-Gly-Gly (SEQ
ID NO:191);
G1y-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa5-His-Ile-
Cys(SEQIDNO:192);
Thr-Xaa5-Xaa,-Xaa,-Cys-Cys-Xaa5-Asn-Xaa5-Xaa5-Cys-Phe-Ala-Thr-Asn-Ser-Asp-Ile-
Cys-
Gly (SEQ ID NO:193);
Asp-Ala-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Gly-Xaa2-His-Gln-Asp-Leu-Cys (SEQ ID
NO:194);
Xaa,-Asp-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-Asp-Leu-Cys (SEQ ID
NO:195);
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Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Ser-Asn-Ala-His-Ile-Cys (SEQ ID
NO:196);
Xaa,-Asp-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-Asp-Met-Cys (SEQ ID
NO:197);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Ile-Cys (SEQ
IDNO:198);
5 Gly-Cys-Cys-Gly-Asn-Xaa5-Ser-Cys-Ser-Ile-His-Ile-Xaa5-Xaa4-Val-Cys-Asn (SEQ
ID
NO:199);
Thr-Asp-Ser-Xaa,-Xaa,-Cys-Cys-Leu-Asp-Ser-Arg-Cys-Ala-Gly-Gln-His-Gln-Asp-Leu-
Cys-Gly (SEQ ID NO:200);
Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Xaa4-Ala-Asn-Asn-Gln-Ala-Xaa4-Cys-Asn (SEQ
ID
10 NO:201);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-V al-Asn-Asn-Xaa5-Asp-Ile-Cys (SEQ ID
NO:202);
Gly-Xaa,-Cys-Cys-Ile-Asn-Asp-Ala-Cys-Arg-Ser-Xaa,-His-Xaa5-Gln-Xaa4-Cys-Ser
(SEQ
ID NO:203);
Gly-Cys-Cys-Xaa4-Asn-Ile-Ala-Cys-Arg-Ile-Asn-Asn-Xaa5-Arg-Xaa4-Cys-Arg (SEQ ID
15 NO:204);
Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Arg-Phe-Asn-Xaa4-Xaa5-Xaa2-Xaa4-Cys-Gly (SEQ
ID
NO:205);
Asp-Xaa,-Cys-Cys-Ala-Ser-Xaa5-Xaa5-Cys-Arg-Leu-Asn-Asn-Xaa5-Xaa4-Val-Cys-His
(SEQ ID NO:206);
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Xaa3-Gln-Asn-Asn-Ala-Xaa,-Xaa4-Cys-Arg-Xaa,-
Ser
(SEQ ID NO:207);
Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Ala-Gln-Asn-Asn-Gln-Asp-Xaa4-Cys (SEQ ID
NO:208);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Arg-Xaa, -Xaa4-Cys-Arg-Xaa,-
Ser
(SEQ ID NO:209);
Asp-Xaa5-Cys-Cys-Ser-Xaa4-Xaa5-Asp-Cys-Gly-Ala-Asn-His-Xaa5-Xaa,-Ile-Cys-Gly
(SEQ
ID NO:210);
Xaa,-Cys-Cys-Ser-Gln-Xaa5-Xaa5-Cys-Arg-Xaa3-Xaa,-His-Xaa5-Xaa,-Leu-Cys-Ser
(SEQ
ID NO:211);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Ile-Cys (SEQ
IDNO:212);
Gly-Cys-Cys-Ser-Asp-Xaa5-Ser-Cys-Asn-Val-Asn-Asn-Xaa5-Asp-Xaa4-Cys (SEQ ID
NO:213);
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Xaa,-Xaa,-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-Asp-Met-Cys-Arg
(SEQ
ID NO:214);
Gly-Gly-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Leu-Val-Asn-His-Leu-Xaa,-Met-Cys (SEQ ID
NO:215);
Arg-Asp-Xaa5-Cys-Cys-Phe-Asn-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa5-Gln-Ile-Cys
(SEQ
ID NO:216);
Cys-Cys-Ser-Asp-Xaa5-Ser-Cys-Xaa3-Arg-Leu-His-Ser-Leu-Ala-Cys-Thr-Gly-Ile-Val-
Asn-
Arg (SEQ ID NO:217);
Cys-Cys-Thr-Asn-Xaa5-Ala-Cys-Leu-Val-Asn-Asn-Ile-Arg-Phe-Cys-Gly(SEQIDNO:218);
Asp-Xaa,-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-His-Gly-Asn-Asn-Arg-Asp-His-Cys-Ala (SEQ
ID NO:219);
Asp-Cys-Cys-Ser-His-Xaa5-Leu-Cys-Arg-Leu-Phe-Val-Xaa5-Gly-Leu-Cys-Ile (SEQ ID
NO:220);
Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Xaa2-Val-Arg-Xaa4-Xaa5-Asp-Leu-Cys-Arg (SEQ
ID
NO:221);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa5-His-Ile-Cys
(SEQIDNO:222);
Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Xaa2-Val-Arg-Xaa4-Ser-Asp-Met-Cys (SEQ ID
NO:223);
Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Xaa2-Val-His-Phe-Xaa5-His-Ser-Cys (SEQ ID
NO:224);
V al-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-V al-Asp-His-Xaa5-Xaa, -Leu-Cys-Arg-Arg-
Arg-
Arg (SEQ ID NO:225);
Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Asn-Leu-Ser-Asn-Xaa5-Gln-Ile-Cys-Arg (SEQ ID
NO:226);
Xaa6-Xaa,-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa,-Ile-Cys-Arg
(SEQ
ID NO:227);
Gly-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Leu-Val-Asn-His-Ile-Arg-Phe-Cys-Gly (SEQ ID
NO:228);
Asp-Cys-Cys-Asp-Asp-Xaa5-Ala-Cys-Thr-Val-Asn-Asn-Xaa5-Gly-Leu-Cys-Thr (SEQ ID
NO:229); and
Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ile-Ala-Xaa2-Asn-Xaa5-His-Met-Cys-Gly-Gly-
Arg-
Arg (SEQ ID NO:230),
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17
wherein Xaa, is Glu or y-carboxy-Glu (Gla); Xaa2 is Lys, N-methyl-Lys, N,N-
dimethyl-Lys or
N,N,N-trimethyl-Lys; Xaa3 is Trp (D or L), halo-Trp or neo-Trp; Xaa4 is Tyr,
nor-Tyr, mono-halo-
Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr; and Xaa5 is Pro or
hydroxy-Pro; Xaa6
is Gln or pyro-Glu; and the C-terminus contains a carboxyl or amide group. The
halo is preferably
bromine, chlorine or iodine, more preferably iodine for Tyr and bromine for
Trp. In addition, the
His residues may be substituted with halo-His; the Arg residues may be
substituted by Lys,
ornithine, homoargine, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or
any unnatural
basic amino acid; the Lys residues may be substituted by Arg, ornithine,
homoargine, N-methyl-Lys,
N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino acid; the
Tyr residues may
be substituted with any unnatural hydroxy containing amino acid; the Ser
residues may be
substituted with Thr; the Thr residues may be substituted with Ser; and the
Phe and Trp residues
may be substituted with any unnatural aromatic amino acid. The Cys residues
may be in D or L
configuration and may optionally be substituted with homocysteine (D or L).
The Tyr residues may
be substituted with the 3-hydroxyl or 2-hydroxyl isomers and corresponding O-
sulpho- and 0-
phospho-derivatives. The acidic amino acid residues may be substituted with
any synthetic acidic
bioisoteric amino acid surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
More specifically, the present invention is directed to the following a-
conotoxin peptides
of general formula III:
SmI: SEQ ID NO:22, wherein Xaa, is Glu and Xaa5 is Pro;
OB-29: SEQ ID NO:23, wherein Xaa, is Glu, Xaa3 is Tyr and Xaa5 is Pro;
Txl.1: SEQ ID NO:24, wherein Xaa, is Glu and Xaa5 is Pro;
R1.IA: SEQ ID NO:25, wherein Xaa, is Glu and Xaa5 is Pro;
R1.1B: SEQ ID NO:26, wherein Xaa, is Glu and Xaa5 is Pro;
Om-9: SEQ ID NO:27, wherein Xaa, is Glu and Xaa5 is Pro;
Om-10: SEQ ID NO:28, wherein Xaa5 is Pro;
Om-21: SEQ ID NO:29, wherein Xaa, is Glu and Xaa5 is Pro;
Om-25: SEQ ID NO:30, wherein Xaa, is Glu and Xaa5 is Pro;
Om-27: SEQ ID NO:31, wherein Xaa, is Glu and Xaa5 is Pro;
Om-28: SEQ ID NO:32, wherein Xaa, is Glu and Xaa5 is Pro;
Btl.2: SEQ ID NO:33, wherein Xaa, is Glu and Xaa5 is Pro;
Btl.4: SEQ ID NO:34, wherein Xaa, is Glu and Xaa5 is Pro;
Dal.1: SEQ ID NO:35, wherein Xaa, is Glu and Xaa5 is Pro;
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18
OB-20: SEQ ID NO:36, wherein Xaa, is Glu, Xaa2 is Lys and Xaa5 is Pro;
TI: SEQ ID NO:37, wherein Xaa, is Glu and Xaa5 is Pro;
TIB: SEQ ID NO:38, wherein Xaa, is Glu and Xaa5 is Pro;
Pnl.l : SEQ ID NO:39, wherein XaaS is Pro;
Pnl.2: SEQ ID NO:40, wherein Xaa, is Glu and Xaa5 is Pro;
TI: SEQ ID NO:41, wherein Xaa2 is Lys and XaaS is Pro;
TIA: SEQ ID NO:43, wherein Xaa5 is Pro;
Dal.2: SEQ ID NO:44, wherein Xaa5 is Pro;
Cr1.2: SEQ ID NO:45, wherein Xaa, is Glu and Xaa5 is Pro;
S11.2: SEQ ID NO:46, wherein Xaa, is Glu, Xaa2 is Lys and XaaS is Pro;
Txl.3: SEQ ID NO:47, wherein Xaa, is Glu and Xaa5 is Pro;
Dal.3: SEQ ID NO:48, wherein Xaa, is Glu and Xaa5 is Pro;
Dal.4: SEQ ID NO:49, wherein Xaa, is Glu, Xaa5 is Pro and Xaa6 is Gln;
Txl.2: SEQ ID NO:50, wherein Xaa5 is Pro;
Om-35: SEQ ID NO:51, wherein Xaa, is Glu and XaaS is Pro;
S1l.1: SEQ ID NO:52, wherein Xaa, is Glu, Xaa3 is Trp, Xaa4 is Tyr and Xaa5 is
Pro;
S11.6: SEQ ID NO:53, wherein Xaa, is Glu, Xaa, is Lys, Xaa4 is Tyr and Xaa5 is
Pro;
S11.7: SEQ ID NO:54, wherein Xaa, is Glu Xaa4 is Tyr and XaaS is Pro;
Bt1.1: SEQ ID NO:55, wherein Xaa, is Glu Xaa4 is Tyr and Xaa5 is Pro;
Bt:1.3: SEQ ID NO:56, wherein Xaa, is Glu Xaa4 is Tyr and XaaS is Pro;
Btl.5: SEQ ID NO:57, wherein Xaa, is Glu Xaa4 is Tyr and Xaa5 is Pro;
A1.4: SEQ ID NO:170, wherein Xaa, is Glu and Xaa5 is Pro;
A1.5: SEQ ID NO:171, wherein Xaa, is Glu and Xaa5 is Pro;
A1.6: SEQ ID NO:172, wherein Xaa, is Glu and Xaa5 is Pro;
Afl.1: SEQ ID NO:173, wherein Xaa, is Glu Xaa4 is Tyr, Xaa5 is Pro and Xaa6 is
Gln;
Afl.2: SEQ ID NO: 174, wherein Xaa, is Glu and Xaa5 is Pro;
Arl.2: SEQ ID NO: 175, wherein Xaa, is Glu, Xaa2 is Lys, Xaa3 is Trp, Xaa4 is
Try
and Xaa5 is Pro;
Arl.3: SEQ ID NO: 176, wherein Xaa, is Glu, Xaa4 is Tyr and Xaa5 is Pro;
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19
Arl.4: SEQ ID NO:177, wherein Xaa, is Glu, Xaaz is Lys, Xaa3 is Tip, Xaa4is
Try
and Xaa5 is Pro;
Arl.5: SEQ ID NO:178, wherein Xaa3 is Glu and Xaa5 is Pro;
Arl.6: SEQ ID NO:179, wherein Xaa, is Glu, Xaaz is Lys, Xaa3 is Trp, Xaa4 is
Try
and Xaa5 is Pro;
Ayl.2: SEQ ID NO:180, wherein Xaa4 is Tyr and Xaa5 is Pro;
Ayl.3: SEQ ID NO:181, wherein Xaa5 is Pro;
Bnl.4: SEQ ID NO:182, wherein Xaa4 is Tyr and Xaa5 is Pro;
Btl.8: SEQ ID NO:183, wherein Xaa, is Glu and Xaa5 is Pro;
Btl.9: SEQ ID NO: 184, wherein Xaa1 is Glu, Xaa4 is Tyr and Xaa5 is Pro;
Cal.3: SEQ ID NO:185, wherein Xaa1 is Glu, Xaa3 is Trp, Xaa4 is Try and Xaa5
is
Pro;
Cal.4: SEQ ID NO:186, wherein Xaa1 is Glu, Xaaz is Lys, Xaa3 is Trp, Xaa4 is
Try,
Xaa5 is Pro and Xaa6 is Gln;
C1.2: SEQ ID NO:187, wherein Xaa1 is Glu and Xaa5 is Pro;
C1.3: SEQ ID NO:188, wherein Xaa4 is Tyr and Xaa5 is Pro;
Epl.2: SEQ ID NO:189, wherein Xaa, is Glu, Xaa2 is Lys, Xaa3 is Trp and Xaa5
is
Pro;
G1.1: SEQ ID NO:190, wherein Xaa5 is Pro;
G1.3: SEQ ID NO:191, wherein Xaa5 is Pro;
Iml.3: SEQ ID NO:192, wherein Xaa5 is Pro;
Lvl.2: SEQ ID NO:193, wherein Xaa1 is Glu and Xaa5 is Pro;
Lvl.3: SEQ ID NO:194, wherein Xaa2 is Lys and Xaa5 is Pro;
Lvl.4: SEQ ID NO:195, wherein Xaa, is Glu and Xaa5 is Pro;
Lvl.6: SEQ ID NO:196, wherein Xaa5 is Pro;
Lvl.7: SEQ ID NO:197, wherein Xaa1 is Glu and Xaa5 is Pro;
Lvl.8: SEQ ID NO:198, wherein Xaa5 is Pro;
Lvl.9: SEQ ID NO:199, wherein Xaa4 is Tyr and Xaa5 is Pro;
Lvl.10: SEQ ID NO:200, wherein Xaa1 is Glu;
Mrl.3: SEQ ID NO:201, wherein Xaa4 is Tyr and Xaa5 is Pro;
Mrl.4: SEQ ID NO:202, wherein Xaa5 is Pro;
Msl.1: SEQ ID NO:203, wherein Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
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Msl.6: SEQ ID NO:204, wherein Xaa4 is Tyr and Xaa5 is Pro;
01.1: SEQ ID NO:205, wherein Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
01.2: SEQ ID NO:206, wherein Xaa, is Glu, Xaa4 is Tyr and Xaa5 is Pro;
01.4: SEQ ID NO:207, wherein Xaa, is Glu, Xaa3 is Trp, Xaa4 is Tyr and Xaa5 is
5 Pro;
01.7: SEQ ID NO:208, wherein Xaa4 is Tyr and Xaa5 is Pro;
01.8: SEQ ID NO:209, wherein Xaa, is Glu, Xaa4 is Tyr and Xaa5 is Pro;
Oml.2: SEQ ID NO:210, wherein Xaa, is Glu, Xaa4 is Tyr and Xaa5 is Pro;
Oml.3: SEQ ID NO:211, wherein Xaa, is Glu, Xaa2 is Lys, Xaa3 is Trp and Xaa5
is
10 Pro;
Om1.4: SEQ ID NO:212, wherein Xaa5 is Pro;
Oml.5: SEQ ID NO:213, wherein Xaa4 is Tyr and Xaa5 is Pro;
Oml.6: SEQ ID NO:214, wherein Xaa, is Glu and Xaa5 is Pro;
P1.4: SEQ ID NO:215, wherein Xaa, is Glu and Xaa5 is Pro;
15 P1.5: SEQ ID NO:216, wherein Xaa5 is Pro;
P1.6: SEQ ID NO:217, wherein Xaa3 is Trp and Xaa5 is Pro;
P1.8: SEQ ID NO:218, wherein Xaa5 is Pro;
Rg 1.1: SEQ ID NO:219, wherein Xaa, is Glu and Xaa5 is Pro;
Rgl.3: SEQ ID NO:220, wherein Xaa5 is Pro;
20 Rgl.4: SEQ ID NO:221, wherein Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
Rgl.5: SEQ ID NO:222, wherein Xaa5 is Pro;
Rgl.8: SEQ ID NO:223, wherein Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is Pro;
Sm1.4: SEQ ID NO:224, wherein Xaa2 is Lys and Xaa5 is Pro;
Sml.5: SEQ ID NO:225, wherein Xaa, is Glu and Xaa5 is Pro;
S I.5: SEQ ID NO:226, wherein Xaa5 is Pro;
Txl.5: SEQ ID NO:227, wherein Xaa, is Glu, Xaa5 is Pro and Xaab is Gln;
T1.1: SEQ ID NO:228, wherein Xaa5 is Pro;
Vrl.3: SEQ ID NO:229, wherein Xaa5 is Pro; and
Tb: SEQ ID NO:230, wherein Xaa2 is Lys and Xaa5 is Pro.
The C-terminus preferably contains a carboxyl group for the peptides OB-29,
Txl.l, RI.1A, R1.1B,
Om-9, Om-10, Om-21, Om-25, Om-27, Om-28, Cr1.2, Om-35, Btl.l, Btl.3, Btl.5,
A1.4, A1.6,
Arl.2, Arl.3, Arl.4, Arl.5, Arl.6, Cal.3, Cal.4, Epl.2, Lvl.9, 01.2, Oml.3,
Oml.6, P1.6, Rgl.l,
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21
Rg1.3, Rgl.4, Sm1.5, Tx1.5 and Vrl.3. The C-terminus of the other peptides
preferably contains
an amide group.
The present invention is also directed to the novel specific a-contoxin
peptides having the
formulas:
Cys-Cys-Thr-Ile-Xaa5-Ser-Cys-Xaa4-Xaa,-Xaa2-Xaa,-Xaa2-Ile-Xaa2-Ala-Cys-Val-Phe
(SEQ
ID NO:231) and
Gly-Cys-Cys-Gly-Asn-Xaa5-Ala-Cys-Ser-Gly-Ser-Ser-Xaa2-Asp-Ala-Xaa5-Ser-Cys
(SEQ
ID NO:232),
wherein Xaa, is Glu or y-carboxy-Glu (Gla); Xaa2 is Lys, N-methyl-Lys, N,N-
dimethyl-Lys or
N,N,N-trimethyl-Lys; Xaa4 is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-
sulpho-Tyr, O-phospho-
Tyr or nitro-Tyr; and Xaa5 is Pro or hydroxy-Pro; and the C-terminus contains
a carboxyl or amide
group. The halo is preferably bromine, chlorine or iodine, more preferably
iodine for Tyr. In
addition, the His residues may be substituted with halo-His; the Arg residues
may be substituted by
Lys, ornithine, homoargine, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-
Lys or any
unnatural basic amino acid; the Lys residues may be substituted by Arg,
ornithine, homoargine, N-
methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural basic amino
acid; the Tyr
residues may be substituted with any unnatural hydroxy containing amino acid;
the Ser residues may
be substituted with Thr; the Thr residues may be substituted with Ser; and the
Phe residues may be
substituted with any unnatural aromatic amino acid. The Cys residues may be in
D or L
configuration and may optionally be substituted with homocysteine (D or L).
The Tyr residues may
be substituted with the 3-hydroxyl or 2-hydroxyl isomers and corresponding O-
sulpho- and 0-
phospho-derivatives. The acidic amino acid residues may be substituted with
any synthetic acidic
bioisoteric amino acid surrogate, e.g., tetrazolyl derivatives of Gly and Ala.
More specifically, the present invention is directed to the following a-
conotoxin peptides:
G1.2: SEQ ID NO:231, wherein Xaa, is Glu, Xaa2 is Lys, Xaa4 is Tyr and Xaa5 is
Pro; and
Rg1.12: SEQ ID NO:232, wherein Xaa2 is Lys and Xaa5 is Pro.
The C-terminus of G1.2 preferably contains a carboxyl group, and the C-
terminus of Rgl.12
preferably contains an amide group.
Examples of unnatural aromatic amino acid include, but are not limited to,
such as nitro-Phe,
4-substituted-Phe wherein the substituent is C1-C3 alkyl, carboxyl,
hyrdroxymethyl, sulphomethyl,
halo, phenyl, -CHO, -CN, -SO3H and -NHAc. Examples of unnatural hydroxy
containing amino
CA 02361534 2007-04-18
22
acid, include, but are not limited to, such as 4-hydroxymethyl-Phe, 4-
hydroxyphenyl-Gly,
2,6- dimethyl-Tyr and 5-amino-Tyr. Examples of unnatural basic amino acids
include, but
are not limited to, N-1-(2-pyrazolinyl)-Arg, 2-(4-piperinyl)-Gly, 2-(4-
piperinyl)-Ala, 2-[3-
(2S)pyrrolininyl)- Gly and 2-[3-(2S) pyrrolininyl)-Ala. These and other
unnatural basic
amino acids, unnatural hydroxy containing amino acids or unnatural aromatic
amino acids are
described in Building Block Index, Version 3.0 (1999 Catalog, pages 4-47 for
hydroxy
containing amino acids and aromatic amino acids and pages 66-87 for basic
amino acids by
and available from RSP Amino Acid Analogues, Inc., Worcester, MA.
Optionally, in the peptides of general formulas I, II and III and the specific
peptides described above, the Asn residues may be modified to contain an N-
glycan and the
Ser and Thr residues may be modified to contain an 0-glycan. In accordance
with the
present invention, a glycan shall mean any N-, S- or O-linked mono-, di-, tri-
, poly- or
oligosaccharide that can be attached to any hydroxy, amino or thiol group of
natural or
modified amino acids by synthetic or enzymatic methodologies known in the art.
The
monosaccharides making up the glycan can include D-allose, D-altrose, D-
glucose, D-
mannose, D-gulose, D-idose, D-galactose, D-talose, D- galactosamine, D-
glucosamine, D-N-
acetyl-glucosamine (G1cNAc), D-N-acetyl-galactosamine (Ga1NAc), D-fucose or D-
arabinose. These saccharides may be structurally modified, e. g., with one or
more O-sulfate,
0-phosphate, O-acetyl or acidic groups, such as sialic acid, including
combinations thereof.
The gylcan may also include similar polyhydroxy groups, such as D-
penicillamine 2,5 and
halogenated derivatives thereof or polypropylene glycol derivatives. The
glycosidic linkage
is beta and 1-4 or 1-3, preferably 1-3. The linkage between the glycan and the
amino acid
may be alpha or beta, preferably alpha and is 1-.
Core 0-glycans have been described by Van de Steen et al. (1998). Mucin type
O-linked oligosaccharides are attached to Ser or Thr (or other hydroxylated
residues of the
present peptides) by a GaINAc residue. The monosaccharide building blocks and
the linkage
attached to this first GaINAc residue define the"core glycans, "of which eight
have been
identified. The type of glycosidic linkage (orientation and connectivities)
are defined for
each core glycan. Suitable glycans and glycan analogs are described further in
U.S.
Patent 6,369,193, filed 19 October 1999. A preferred glycan is Gal(0l---
3)GalNAc
CA 02361534 2007-04-18
23
Optionally, in the peptides of general formulas I and II and the specific
peptides
described above, pairs of Cys residues may be replaced pairwise with Ser/(Glu
or Asp) or
Lys/(Glu or Asp) combinations. Sequential coupling by known methods (Barnay et
al., 2000;
Hruby et al., 1994; Bitan et al., 1997) allows replacement of native Cys
bridges with lactam
bridges.
The present invention is further directed to propeptides and nucleic acid
sequences
encoding the propeptides or peptides as described in further detail herein.
DETAILED DESCRIPTION OF THE INVENTION
The invention relates to relatively short peptides (termed a-conotoxins
herein),
about 10-30 residues in length, which are naturally available in minute
amounts in the venom
of the cone snails or analogous to the naturally available peptides, and which
preferably
include two disulfide bonds.
The present invention, in another aspect, relates to a pharmaceutical
composition
comprising an effective amount of an a -conotoxin peptide. Such a
pharmaceutical
composition has the capability of acting as antagonists for nicotinic
acetylcholine receptors.
In one aspect, the a-conotoxins with specificity for neuromuscular junction
nicotinic
acetylcholine receptors are used as neuromuscular blocking agents for use in
conjunction
with surgery, as disclosed in U.S. patent 6,268,473, filed 21 January 2000
(Attorney Docket
No. 2314-178.A) and international patent publication no.WO 00/43409, filed 21
January
2000 (Attorney Docket No. 2314-138. PCT). In a second aspect, additional a -
conotoxins
and uses for them have been described in U. S. Patent Nos. 4,447, 356 (Olivera
et al., 1984);
5,432,155; 5,514,774.
In a third aspect additional uses for a-conotoxins are described in U.S.
Patent
No. 6,265,541, filed 22 December 1998. In this application, a-conotoxins with
specificity for
neuronal nicotinic acetylcholine receptors are used for treating disorders
regulated at
neuronal nicotinic acetylcholine receptors. Such disorders include, but are
not limited to,
cardiovascular disorders, gastric motility disorders, urinary incontinence,
nicotine addiction,
mood disorders (such as bipolar disorder, unipolar depression, dysthymia and
seasonal
CA 02361534 2007-04-18
23a
effective disorder) and small cell lung carcinoma, as well as the localization
of small cell lung
carcinoma.
The a-conotoxin peptides described herein are sufficiently small to be
chemically
synthesized. General chemical syntheses for preparing the foregoing a -
conotoxin peptides
are described hereinafter. Various ones of the a-conotoxin peptides can also
be obtained by
isolation
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24
and purification from specific Conus species using the technique described in
U.S. Patent No.
4,447,356 (Olivera et al., 1984).
Although the a-conotoxin peptides of the present invention can be obtained by
purification
from cone snails, because the amounts of a-conotoxin peptides obtainable from
individual snails
are very small, the desired substantially pure a-conotoxin peptides are best
practically obtained in
commercially valuable amounts by chem cal synthesis using solid-phase
strategy. For example, the
yield from a single cone snail may be a .out 10 micrograms or less of a-
conotoxin peptide. By
"substantially pure" is meant that the peptide is present in the substantial
absence of other biological
molecules of the same type; it is preferably present in an amount of at least
about 85% purity and
preferably at least about 95% purity. Chemical synthesis of biologically
active a-conotoxin peptides
depends of course upon correct determination of the amino acid sequence.
The a-conotoxin peptides can also be produced by recombinant DNA techniques
well known
in the art. Such techniques are described by Sambrook et al. (1989). The
peptides produced in this
manner are isolated, reduced if necessary, and oxidized to form the correct
disulfide bonds.
One method of forming disulfide bonds in the conantokin peptides of the
present invention
is the air oxidation of the linear peptides for prolonged periods under cold
room temperatures or at
room temperature. This procedure results in the creation of a substantial
amount of the bioactive,
disulfide-linked peptides. The oxidized peptides are fractionated using
reverse-phase high
performance liquid chromatography (HPLC) or the like, to separate peptides
having different linked
configurations. Thereafter, either by comparing these fractions with the
elution of the native material
or by using a simple assay, the particular fraction having the correct linkage
for maximum biological
potency is easily determined. However, because of the dilution resulting from
the presence of other
fractions of less biopotency, a somewhat higher dosage may be required.
The peptides are synthesized by a suitable method, such as by exclusively
solid-phase
techniques, by partial solid-phase techniques, by fragment condensation or by
classical solution
couplings.
In conventional solution phase peptide synthesis, the peptide chain can be
prepared by a
series of coupling reactions in which constituent amino acids are added to the
growing peptide chain
in the desired sequence. Use of various coupling reagents, e.g.,
dicyclohexylcarbodiimide or
diisopropylcarbonyldimidazole, various active esters, e.g., esters of N-
hydroxyphthalimide or N-
hydroxy-succinimide, and the various cleavage reagents, to carry out reaction
in solution, with
subsequent isolation and purification of intermediates, is well known
classical peptide methodology.
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WO 00/44776 PCT/US00/01979
Classical solution synthesis is described in detail in the treatise, "Methoden
der Organischen Chemie
(Houben-Weyl): Synthese von Peptiden," (1974). Techniques of exclusively solid-
phase synthesis
are set forth in the textbook, "Solid-Phase Peptide Synthesis," (Stewart and
Young, 1969), and are
exemplified by the disclosure of U.S. Patent 4,105,603 (Vale et al., 1978).
The fragment
5 condensation method of synthesis is exemplified in U.S. Patent 3,972,859
(1976). Other available
syntheses are exemplified by U.S. Patents No. 3,842,067 (1974) and 3,862,925
(1975). The
synthesis of peptides containing y-carboxyglutamic acid residues is
exemplified by Rivier et al.
(1987), Nishiuchi et al. (1993) and Zhou et al. (1996).
Common to such chemical syntheses is the protection of the labile side chain
groups of the
10 various amino acid moieties with suitable protecting groups which will
prevent a chemical reaction
from occurring at that site until the group is ultimately removed. Usually
also common is the
protection of an a-amino group on an amino acid or a fragment while that
entity reacts at the
carboxyl group, followed by the selective removal of the a-amino protecting
group to allow
subsequent reaction to take place at that location. Accordingly, it is common
that, as a step in such
15 a synthesis, an intermediate compound is produced which includes each of
the amino acid residues
located in its desired sequence in the peptide chain with appropriate side-
chain protecting groups
linked to various ones of the residues having labile side chains.
As far as the selection of a side chain amino protecting group is concerned,
generally one
is chosen which is not removed during deprotection of the a-amino groups
during the synthesis.
20 However, for some amino acids, e.g., His, protection is not generally
necessary. In selecting a
particular side chain protecting group to be used in the synthesis of the
peptides, the following
general rules are followed: (a) the protecting group preferably retains its
protecting properties and
is not split off under coupling conditions, (b) the protecting group should be
stable under the
reaction conditions selected for removing the a-amino protecting group at each
step of the synthesis,
25 and (c) the side chain protecting group must be removable, upon the
completion of the synthesis
containing the desired amino acid sequence, under reaction conditions that
will not undesirably alter
the peptide chain.
It should be possible to prepare many, or even all, of these peptides using
recombinant DNA
technology. However, when peptides are not so prepared, they are preferably
prepared using the
Merrifield solid-phase synthesis, although other equivalent chemical syntheses
known in the art can
also be used as previously mentioned. Solid-phase synthesis is commenced from
the C-terminus
of the peptide by coupling a protected a-amino acid to a suitable resin. Such
a starting material can
CA 02361534 2001-07-26
WO 00/44776 PCT/US00/01979
26
be prepared by attaching an a-amino-protected amino acid by an ester linkage
to a chloromethylated
resin or a hydroxymethyl resin, or by an amide bond to a benzhydrylamine (BHA)
resin or para-
methylbenzhydrylamine (MBHA) resin. Preparation of the hydroxymethyl resin is
described by
Bodansky et al. (1966). Chloromethylated resins are commercially available
from Bio Rad
Laboratories (Richmond, CA) and from Lab. Systems, Inc. The preparation of
such a resin is
described by Stewart and Young (1969). BHA and MBHA resin supports are
commercially
available, and are generally used when the desired polypeptide being
synthesized has an
unsubstituted amide at the C-terminus. Thus, solid resin supports may be any
of those known in the
art, such as one having the formulae -O-CH2-resin support, -NH BHA resin
support, or -NH-MBHA
resin support. When the unsubstituted amide is desired, use of a BHA or MBHA
resin is preferred,
because cleavage directly gives the amide. In case the N-methyl amide is
desired, it can be
generated from an N-methyl BHA resin. Should other substituted amides be
desired, the teaching
of U.S. Patent No. 4,569,967 (Kornreich et al., 1986) can be used, or should
still other groups than
the free acid be desired at the C-terminus, it may be preferable to synthesize
the peptide using
classical methods as set forth in the Houben-Weyl text (1974).
The C-terminal amino acid, protected by Boc or Fmoc and by a side-chain
protecting group,
if appropriate, can be first coupled to a chloromethylated resin according to
the procedure set forth
in K. Horiki et al. (1978), using KF in DMF at about 60 C for 24 hours with
stirring, when a peptide
having free acid at the C-terminus is to be synthesized. Following the
coupling of the BOC-
protected amino acid to the resin support, the a-amino protecting group is
removed, as by using
trifluoroacetic acid (TFA) in methylene chloride or TFA alone. The
deprotection is carried out at
a temperature between about 0 C and room temperature. Other standard cleaving
reagents, such as
HCl in dioxane, and conditions for removal of specific a-amino protecting
groups may be used as
described in Schroder & Lubke (1965).
After removal of the a-amino-protecting group, the remaining a-amino- and side
chain-
protected amino acids are coupled step-wise in the desired order to obtain the
intermediate
compound defined hereinbefore, or as an alternative to adding each amino acid
separately in the
synthesis, some of them may be coupled to one another prior to addition to the
solid phase reactor.
Selection of an appropriate coupling reagent is within the skill of the art.
Particularly suitable as
a coupling reagent is N,N'-dicyclohexylcarbodiimide (DCC, DIC, HBTU, HATU,
TBTU in the
presence of HoBt or HoAt).
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WO 00/44776 PCT/US00/01979
27
The activating reagents used in the solid phase synthesis of the peptides are
well known in
the peptide art. Examples of suitable activating reagents are carbodiimides,
such as N,N'-
diisopropylcarbodiimide and N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide.
Other activating
reagents and their use in peptide coupling are described by Schroder & Lubke
(1965) and Kapoor
(1970).
Each protected amino acid or amino acid sequence is introduced into the solid-
phase reactor
in about a twofold or more excess, and the coupling may be carried out in a
medium of
dimethylformamide (DMF):CH2C12 (1:1) or in DMF or CH2Cl2 alone. In cases where
intermediate
coupling occurs, the coupling procedure is repeated before removal of the a-
amino protecting group
prior to the coupling of the next amino acid. The success of the coupling
reaction at each stage of
the synthesis, if performed manually, is preferably monitored by the ninhydrin
reaction, as described
by Kaiser et al. (1970). Coupling reactions can be performed automatically, as
on a Beckman 990
automatic synthesizer, using a program such as that reported in Rivier et al.
(1978).
After the desired amino acid sequence has been completed, the intermediate
peptide can be
removed from the resin support by treatment with a reagent, such as liquid
hydrogen fluoride or
TFA (if using Fmoc chemistry), which not only cleaves the peptide from the
resin but also cleaves
all remaining side chain protecting groups and also the a-amino protecting
group at the N-terminus
if it was not previously removed to obtain the peptide in the form of the free
acid. If Met is present
in the sequence, the Boc protecting group is preferably first removed using
trifluoroacetic acid
(TFA)/ethanedithiol prior to cleaving the peptide from the resin with HF to
eliminate potential S-
alkylation. When using hydrogen fluoride or TFA for cleaving, one or more
scavengers such as
anisole, cresol, dimethyl sulfide and methylethyl sulfide are included in the
reaction vessel.
Cyclization of the linear peptide is preferably affected, as opposed to
cyclizing the peptide
while a part of the peptido-resin, to create bonds between Cys residues. To
effect such a disulfide
cyclizing linkage, fully protected peptide can be cleaved from a
hydroxymethylated resin or a
chloromethylated resin support by ammonolysis, as is well known in the art, to
yield the fully
protected amide intermediate, which is thereafter suitably cyclized and
deprotected. Alternatively,
deprotection, as well as cleavage of the peptide from the above resins or a
benzhydrylamine (BHA)
resin or a methylbenzhydrylamine (MBHA), can take place at 0 C with
hydrofluoric acid (HF) or
TFA, followed by oxidation as described above.
The peptides are also synthesized using an automatic synthesizer. Amino acids
are
sequentially coupled to an MBHA Rink resin (typically 100 mg of resin)
beginning at the C-
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WO 00/44776 PCTIUSOO/01979
28
terminus using an Advanced Chemtech 357 Automatic Peptide Synthesizer.
Couplings are carried
out using 1,3-diisopropylcarbodimide in N-methylpyrrolidinone (NMP) or by 2-
(1H-benzotriazole-
1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) and diethylisopro-
pylethylamine
(DIEA). The FMOC protecting group is removed by treatment with a 20% solution
of piperidine
in dimethylformamide(DMF). Resins are subsequently washed with DMF (twice),
followed by
methanol and NMP.
Pharmaceutical compositions containing a compound of the present invention or
its
pharmaceutically acceptable salts as the active ingredient can be prepared
according to conventional
pharmaceutical compounding techniques. See, for example, Remington's
Pharmaceutical Sciences,
18th Ed. (1990, Mack Publishing Co., Easton, PA). Typically, an antagonistic
amount of the active
ingredient will be admixed with a pharmaceutically acceptable carrier. The
carrier may take a wide
variety of forms depending on the form of preparation desired for
administration, e.g., intravenous,
oral or parenteral. The compositions may further contain antioxidizing agents,
stabilizing agents,
preservatives and the like.
For oral administration, the compounds can be formulated into solid or liquid
preparations
such as capsules, pills, tablets, lozenges, melts, powders, suspensions or
emulsions. In preparing
the compositions in oral dosage form, any of the usual pharmaceutical media
may be employed,
such as, for example, water, glycols, oils, alcohols, flavoring agents,
preservatives, coloring agents,
suspending agents, and the like in the case of oral liquid preparations (such
as, for example,
suspensions, elixirs and solutions); or carriers such as starches, sugars,
diluents, granulating agents,
lubricants, binders, disintegrating agents and the like in the case of oral
solid preparations (such as,
for example, powders, capsules and tablets). Because of their ease in
administration, tablets and
capsules represent the most advantageous oral dosage unit form, in which case
solid pharmaceutical
carriers are obviously employed. If desired, tablets may be sugar-coated or
enteric-coated by
standard techniques. The active agent can be encapsulated to make it stable to
passage through the
gastrointestinal tract while at the same time allowing for passage across the
blood brain barrier. See
for example, WO 96/11698.
For parenteral administration, the compound may be dissolved in a
pharmaceutical carrier
and administered as either a solution or a suspension. Illustrative of
suitable carriers are water,
saline, dextrose solutions, fructose solutions, ethanol, or oils of animal,
vegetative or synthetic
origin. The carrier may also contain other ingredients, for example,
preservatives, suspending
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WO 00/44776 PCTIUSOO/01979
29
agents, solubilizing agents, buffers and the like. When the compounds are
being administered
intrathecally, they may also be dissolved in cerebrospinal fluid.
The active agent is preferably administered in an therapeutically effective
amount. The
actual amount administered, and the rate and time-course of administration,
will depend on the
nature and severity of the condition being treated. Prescription of treatment,
e.g. decisions on
dosage, timing, etc., is within the responsibility of general practitioners or
spealists, and typically
takes account of the disorder to be treated, the condition of the individual
patient, the site of
delivery, the method of administration and other factors known to
practitioners. Examples of
techniques and protocols can be found in Remington's Parmaceutical Sciences.
Typically the
conopeptides of the present invention exhibit their effect at a dosage range
from about 0.001 mg/kg
to about 250 mg/kg, preferably from about 0.05 mg/kg to about 100 mg/kg of the
active ingredient,
more preferably from a bout 0.1 mg/kg to about 75 mg/kg. A suitable dose can
be administered in
multiple sub-doses per day. Typically, a dose or sub-dose may contain from
about 0.1 mg to about
500 mg of the active ingredient per unit dosage form. A more preferred dosage
will contain from
about 0.5 mg to about 100 mg of active ingredient per unit dosage form.
Dosages are generally
initiated at lower levels and increased until desired effects are achieved.
Alternatively, targeting therapies may be used to deliver the active agent
more specifically
to certain types of cell, by the use of targeting systems such as antibodies
or cell specific ligands.
Targeting may be desirable for a variety of reasons, e.g. if the agent is
unacceptably toxic, or if it
would otherwise require too high a dosage, or if it would not otherwise be
able to enter the target
cells.
The active agents, which are peptides, can also be administered in a cell
based delivery
system in which a DNA sequence encoding an active agent is introduced into
cells designed for
implantation in the body of the patient, especially in the spinal cord region.
Suitable delivery
systems are described in U.S. Patent No. 5,550,050 and published PCT
Application Nos. WO
92/19195, WO 94/25503, WO 95/01203, WO 95/05452, WO 96/02286, WO 96/02646, WO
96/40871, WO 96/40959 and WO 97/12635. Suitable DNA sequences can be prepared
synthetically
for each active agent on the basis of the developed sequences and the known
genetic code.
CA 02361534 2007-04-18
EXAMPLES
The present invention is described by reference to the following Examples,
which
are offered by way of illustration and are not intended to limit the invention
in any manner.
Standard techniques well known in the art or the techniques specifically
described below
were utilized.
EXAMPLE 1
Isolation of a-Conotoxins
Crude venom was extracted from venom ducts (Cruz et al., 1976), and the
components were purified as previously described (Cartier et al., 1996a). The
crude extract
from venom ducts was purified by reverse phase liquid chromatography (RPLC)
using a
Vydac* C18 semi-preparative column (10 x 250 mm) and elution with a linear
gradient of
acetonitrile in 0.1 %TFA. Further purification of bioactive peaks was done on
a Vydac C18
analytical column (4.6 x 220 mm) eluted with a gradient of acetonitrile in
0.1% TFA. The
effluents were monitored at 220 nm. Peaks were collected, and aliquots were
assayed for
activity. Activity was monitored by assessing block of OP 4 nAChRs expressed
in Xenopus
oocytes.
The amino acid sequence of the purified peptides were determined by standard
methods. The purified peptides were reduced and alkylated prior to sequencing
by automated
Edman degradation on an Applied Biosystems 477A Protein Sequencer with a 120A
Analyzer (DNA/Peptide Facility, University of Utah) (Martinez et al., 1995;
Shon et al.,
1994).
In accordance with this method, peptides MII, AuIA, AuIB, AuIC, MAR-1,
MAR-2, TI, OB- 29, Epl, S1.1, Bnl.1, Bnl.2, Cal.l, Cal.2, Cnl.l, Cnl.2 and
Sml.3 were
obtained.
* Trademark
CA 02361534 2007-04-18
30a
EXAMPLE 2
Synthesis of Conopeptides
The synthesis of conopeptides, either the mature toxins or the precursor
peptides,
was separately performed using conventional protection chemistry as described
by Cartier et
al. (1996). Briefly, the linear chains were built on Rink amide resin by Fmoc
procedures with
2-(1H-benzotriol-l-yl)-1,1,3,3,-tetramethyluronium tetrafluoroborated coupling
using an ABI
model 430A peptide sythesizer with amino acid derivatives purchased from
Bachem
(Torrence CA). Orthogonal protection was used on cysteines: Cys3 and Cys16
were protected
as the stable Cys(S-acetamidomethyl), while Cyst and Cys8 were protected as
the acid-labile
Cys (S-trityl). After removal of the terminal Fmoc protecting group and
cleavage of the
peptides from the resins, the
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WO 00/44776 PCT/US00/01979
31
released peptides were precipitated by filtering the reaction mixture into -10
C methyl t-butyl ether,
which removed the protecting groups except on Cys3 and Cys16. The peptides
were dissolved in
0.1% TFA and 60% acetonitrile and purified by RPLC on a Vydac C18 preparative
column (22 x 250
mm) and eluted at a flow rate of 20 mL/min with a gradient of acetonitrile in
0.1 % TFA.
The disulfide bridges in the three conopeptides were formed as described in
Cartier et al.
(1996). Briefly, the disulfide bridges between Cyst and Cys8 were formed by
air oxidation which
was judged to be complete by analytical RPLC. The monocyclic peptides were
purified by RPLC
on a Vydac C18 prepartive column (22 x 250 mm) and eluted with a gradient of
acetonitrile in 0.1%
TFA. Removal of S-acetamidomethyl groups and closure of the disulfide bridge
between Cys3 and
Cys16 was carried out simultaneously be iodine oxidation. The cyclic peptides
were purified by
RPLC on a Vydac C18 prepartive column (22 x 250 mm) and eluted with a gradient
of acetonitrile
in 0.1 % TFA.
EXAMPLE 3
Isolation of DNA Encoding a-Conotoxins
DNA coding for a-conotoxins was isolated and cloned in accordance with
conventional
techniques using general procedures well known in the art, such as described
in Olivera et al. (1996).
Alternatively, cDNA libraries was prepared from Conus venom duct using
conventional techniques.
DNA from single clones was amplified by conventional techniques using primers
which correspond
approximately to the M13 universal priming site and the M13 reverse universal
priming site. Clones
having a size of approximately 300 nucleotides were sequenced and screened for
similarity in
sequence to known a-conotoxins. The DNA sequences and encoded propeptide or
peptide
sequences are set forth in Tables 1-134.
TABLE 1
DNA Sequence (SEQ ID NO:58) and Protein Sequence (SEQ ID NO:59) of MII
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac gac
Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp
aaa gcg tct gac gtg atc acg ctg gcc ctc aag gga tgc tgt tcc aac
Lys Ala Ser Asp Val Ile Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn
cct gtc tgt cac ttg gag cat tca aac ctt tgt ggt aga aga cgc
Pro Val Cys His Leu Glu His Ser Asn Leu Cys Gly Arg Arg Arg
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32
tgatgctcca ggaccctctg aaccacgacg ttcgagca
TABLE 2
DNA Sequence (SEQ ID NO:60) and Protein Sequence (SEQ ID NO:61) of AuIA
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca gat cgt gca tct gat ggc agg aag gac gca gcg tct ggc
Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Lys Asp Ala Ala Ser Gly
ctg atc get ctg acc atc aag gga tgc tgt tct tat cct ccc tgt ttc
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe
gcg act aat tca gac tat tgt ggt tgacgacgct gatgctccag gaccctctga
Ala Thr Asn Ser Asp Tyr Cys Gly
accacgacgt
TABLE
DNA Sequence (SEQ ID NO:62) and Protein Sequence (SEQ ID NO:63) of AuIB
atg ttc acc gtg ttt ctg ttg gtc gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca gat cgt gca tct gat ggc agg aag gac gca gcg tct ggc
Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Lys Asp Ala Ala Ser Gly
ctg att get ctg acc atg aag gga tgc tgt tct tat cct ccc tgt ttc
Leu Ile Ala Leu Thr Met Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe
gcg act aat cca gac tgt ggt cga cga cgc tgatgctcca ggaccctctg
Ala Thr Asn Pro Asp Cys Gly Arg Arg Arg
aaccacgacg t
TABLE 4
DNA Sequence (SEQ ID NO:64) and Protein Sequence (SEQ ID NO:65) of Tx1.3
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc tct tca ggt cgt agt aca ttt cgt ggc agg aat gcc gca gcc aaa
Phe Ser Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys
gcg tct ggc ctg gtc agt ctg act gac agg aga cca gaa tgc tgt agt
Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser
gat cct cgc tgt aac tcg agt cat cca gaa ctt tgt ggt gga aga cgc
Asp Pro Arg Cys Asn Ser Ser His Pro Glu Leu Cys Gly Gly Arg Arg
tgatgctcca ggaccctctg aaccacgacg t
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TABLE 5
DNA Sequence (SEQ ID NO:66) and Protein Sequence (SEQ ID NO:67) of Tx1.2
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc gcc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Ala Val Val Ser
ttc act tca gat cgt gca tct gat gac ggg aaa gcc get gcg tct gac
Phe Thr Ser Asp Arg Ala Ser Asp Asp Gly Lys Ala Ala Ala Ser Asp
ctg atc act ctg acc atc aag gga tgc tgt tct cgt cct ccc tgt atc
Leu Ile Thr Leu Thr Ile Lys Gly Cys Cys Ser Arg Pro Pro Cys Ile
gcg aat aat cca gac ttg tgt ggt tgacgacgct gatgctccag aacggtctga
Ala Asn Asn Pro Asp Leu Cys Gly
accacgacgt tcgagcaatg ttcaccgtgt ttctgttggt tgtctt
TABLE 6
DNA Sequence (SEQ ID NO:68) and Protein Sequence (SEQ ID NO:69) of Txl.1
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca ggt cgt agt aca ttt cgt ggc agg aat gcc gca gcc aaa
Phe Thr Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys
gcg tct ggc ctg gtc agt ctg act gac agg aga cca caa tgc tgt tct
Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser
cat cct gcc tgt aac gta gat cat cca gaa att tgt cgt tgaagacgct
His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Arg
gatgctccag gaccctctga accacgacgt
TABLE 7
DNA Sequence (SEQ ID NO:70) and Protein Sequence (SEQ ID NO:71) of R1.1A
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca ggt cgt cgt aca ttt cat ggc agg aat gcc gca gcc aaa
Phe Thr Ser Gly Arg Arg Thr Phe His Gly Arg Asn Ala Ala Ala Lys
gcg tct ggc ctg gtc agt ctg act gac agg aga cca gaa tgc tgt tct
Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser
cat cct gcc tgt aac gta gat cat cca gaa att tgt cgt tgaagacgct
His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Arg
gatgctccag gaccctctga accacgacgt
TABLE 8
DNA Sequence (SEQ ID NO:72) and Protein Sequence (SEQ ID NO:73) of R1.1B
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
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WO 00/44776 PCTIUSOO/01979
34
ttc act tca ggt cgt agt aca ttt cgt ggc agg aat gcc gca gcc aaa
Phe Thr Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys
gcg tct ggc ctg gtc agt ctg act gac agg aga cca caa tgc tgt tct
Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Gin Cys Cys Ser
cat cct gcc tgt aac gta gat cat cca gaa att tgc gat tgaagacgct
His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Asp
gatgctccag gaccctctga accacgacgt
TABLE 9
DNA Sequence (SEQ ID NO:74) and Protein Sequence (SEQ ID NO:75) of S1.1
atg ttc act gtg ttt ctg ttg gtt gtc ttg gca atc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Ile Thr Val Val Ser
ttc cct tta gat cgt gaa tct gat ggc gcg aat gcc gaa gcc cgc acc
Phe Pro Leu Asp Arg Glu Ser Asp Gly Ala Asn Ala Glu Ala Arg Thr
cac gat cat gag aag cac gca ctg gac cgg aat gga tgc tgt agg aat
His Asp His Glu Lys His Ala Leu Asp Arg Asn Gly Cys Cys Arg Asn
cct gcc tgt gag agc cac aga tgt ggt tgacgacgct gatgctccag
Pro Ala Cys Glu Ser His Arg Cys Gly
gaccctctga accacgacgt tcgagca
TABLE 10
DNA Sequence (SEQ ID NO:76) and Protein Sequence (SEQ ID NO:77) of Bnl.1
atg ttc acc atg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Met Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc get tca gat cgt gca tct gat ggc agg aat gcc gca gcc aag gac
Phe Ala Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp
aaa gcg tct gac ctg gtc get ctg acc gtc aag gga tgc tgt tct cat
Lys Ala Ser Asp Leu Val Ala Leu Thr Val Lys Gly Cys Cys Ser His
cct gcc tgt agc gtg aat aat cca gac att tgt ggt tgaagacgct
Pro Ala Cys Ser Val Asn Asn Pro Asp Ile Cys Gly
gatgctccag gaccctctga accacgacgt tcgagca
TABLE 11
DNA Sequence (SEQ ID NO:78) and Protein Sequence (SEQ ID NO:79) of Bnl.2
aaa gaa tgc tgt act cat cct gcc tgt cac gtg agt cat cca gaa ctc
Lys Glu Cys Cys Thr His Pro Ala Cys His Val Ser His Pro Glu Leu
tgt ggt tgaaaagcga cgtgacgctc caggaccctc tgaaccacga cgttcgagca
Cys Gly
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TABLE 12
DNA Sequence (SEQ ID NO:80) and Protein Sequence (SEQ ID NO:81) of Bnl.3
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca act get gtt ctt cca
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Ala Val Leu Pro
5 gtc act tta gat cgt gca tct gat gga agg aat gca gca gcc aac gcc
Val Thr Leu Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala
aaa acg cct cgc ctg atc gcg cca ttc atc agg gat tat tgc tgt cat
Lys Thr Pro Arg Leu Ile Ala Pro Phe Ile Arg Asp Tyr Cys Cys His
aga ggt ccc tgt atg gta tgg tgt ggt tgaagccgct gctgctccag
10 Arg Gly Pro Cys Met Val Trp Cys Gly
gaccctctga accac
TABLE 13
DNA Sequence (SEQ ID NO:82) and Protein Sequence (SEQ ID NO:83) of Cal.1
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtg gtt tcc
15 Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca gat cgt get tct gat ggc agg aat gcc gca gcc aac gcg
Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala
ttt gac ctg atc get ctg atc gcc agg caa aat tgc tgt agc att ccc
Phe Asp Leu Ile Ala Leu Ile Ala Arg Gln Asn Cys Cys Ser Ile Pro
20 agc tgt tgg gag aaa tat aaa tgt agt taa
Ser Cys Trp Glu Lys Tyr Lys Cys Ser
TABLE 14
DNA Sequence (SEQ ID NO:84) and Protein Sequence (SEQ ID NO:85) of Cal.2
25 atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtg gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca gat cgt gcg tct gaa ggc agg aat get gca gcc aag gac
Phe Thr Ser Asp Arg Ala Ser Glu Gly Arg Asn Ala Ala Ala Lys Asp
aaa gcg tct gac ctg gtg get ctg aca gtc agg gga tgc tgt gcc att
30 Lys Ala Ser Asp Leu Val Ala Leu Thr Val Arg Gly Cys Cys Ala Ile
cgt gaa tgt cgc ttg cag aat gca gcg tat tgt ggt gga ata tac
Arg Glu Cys Arg Leu Gln Asn Ala Ala Tyr Cys Gly Gly Ile Tyr
.tgatgctcca ggaccctctg aaccacgacg
TABLE 15
35 DNA Sequence (SEQ ID NO:86) and Protein Sequence (SEQ ID NO:87) of TIB
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
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36
ttc cct tca gat att gca act gag ggc agg aat gcc gca gcc aaa gcg
Phe Pro Ser Asp Ile Ala Thr Glu Gly Arg Asn Ala Ala Ala Lys Ala
ttt gac ctg ata tct tcg atc gtc aag aaa gga tgc tgt tcc cat cct
Phe Asp Leu Ile Ser Ser Ile Val Lys Lys Gly Cys Cys Ser His Pro
gcc tgt tcg ggg aat aat cca gaa ttt tgt cgt caa ggt cgc
Ala Cys Ser Gly Asn Asn Pro Glu Phe Cys Arg Gln Gly Arg
tgatgctcca ggaccctctg aaccacgacg t
TABLE 16
DNA Sequence (SEQ ID NO:88) and Protein Sequence (SEQ ID NO:89) of TIA
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc cct tca gat ata gca act gag ggc agg aat gcc gca gcc aaa gcg
Phe Pro Ser Asp Ile Ala Thr Glu Gly Arg Asn Ala Ala Ala Lys Ala
ttt gac ctg ata tct tcg atc gtc agg aaa gga tgc tgt tcc aat ccc
Phe Asp Leu Ile Ser Ser Ile Val Arg Lys Gly Cys Cys Ser Asn Pro
gcc tgt gcg ggg aat aat cca cat gtt tgt cgt caa ggt cgc
Ala Cys Ala Gly Asn Asn Pro His Val Cys Arg Gln Gly Arg
tgatgctcca ggaccctctg aaccacgacg t
TABLE 17
DNA Sequence (SEQ ID NO:90) and Protein Sequence (SEQ ID NO:91) of Sll.1
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc aat tca gat cgt gat cca gca tta ggt ggc agg aat get gca gcc
Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala
aaa gcg tct gac aag atc get tcg acc ctc aag aga aga gga tgc tgt
Lys Ala Ser Asp Lys Ile Ala Ser Thr Leu Lys Arg Arg Gly Cys Cys
tcg tat ttt gac tgt aga atg atg ttt cca gaa atg tgt ggt tgg cga
Ser Tyr Phe Asp Cys Arg Met Met Phe Pro Glu Met Cys Gly Trp Arg
ggc tgatgctcca ggaccctctg aaccacgacg t
Gly
TABLE 18
DNA Sequence (SEQ ID NO:92) and Protein Sequence (SEQ ID NO:93) of S11.2
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc aat tca gat cgt gat cca gca tta ggt ggc agg aat get gca gcc
Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala
ata gcg tct gac aag atc get tcg acc ctc agg aga gga gga tgc tgt
Ile Ala Ser Asp Lys Ile Ala Ser Thr Leu Arg Arg Gly Gly Cys Cys
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tct ttt cct gcc tgt aga aag tat cgt cca gaa atg tgt ggt gga cga
Ser Phe Pro Ala Cys Arg Lys Tyr Arg Pro Glu Met Cys Gly Gly Arg
cgc tgatgctcca ggaccctctg aaccacgacg t
Arg
TABLE 19
DNA Sequence (SEQ ID NO:94) and Protein Sequence (SEQ ID NO:95) of S11.3
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca gat cat gaa tct gat cgc ggt gat gcc caa acc atc caa
Phe Thr Ser Asp His Glu Ser Asp Arg Gly Asp Ala Gln Thr Ile Gln
gaa gtg ttt gag atg ttc get ctg gac agc gat gga tgc tgt tgg cat
Glu Val Phe Glu Met Phe Ala Leu Asp Ser Asp Gly Cys Cys Trp His
cct get tgt ggc aga cac tat tgt ggt cga aga cgc tgatgctcca
Pro Ala Cys Gly Arg His Tyr Cys Gly Arg Arg Arg
ggaccctctg aaccacgacg t
TABLE 20
DNA Sequence (SEQ ID NO:96) and Protein Sequence (SEQ ID NO:97) of S11.6
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc aat tca gat cgt gat cca gca tta ggt ggc agg aat get gca gcc
Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala
ata gcg tct gac aag atc get tcg acc ctc agg aga gga gga tgc tgt
Ile Ala Ser Asp Lys Ile Ala Ser Thr Leu Arg Arg Gly Gly Cys Cys
tct ttt get gcc tgt aga aag tat cgt cca gaa atg tgt ggt gga cga
Ser Phe Ala Ala Cys Arg Lys Tyr Arg Pro Glu Met Cys Gly Gly Arg
cgc tgatgct
Arg
TABLE 21
DNA Sequence (SEQ ID NO:98) and Protein Sequence (SEQ ID NO:99) of S11.7
atg ttc acc gtg ttt ctg ttg gtt ctc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Leu Leu Ala Thr Thr Val Val Ser
ttc aat tca gat cgt gca tta ggt ggc agg aat get gca gcc aaa gcg
Phe Asn Ser Asp Arg Ala Leu Gly Gly Arg Asn Ala Ala Ala Lys Ala
tct gac aag atc ctt tcg aac ctc agg aga gga gga tgc tgt ttt cat
Ser Asp Lys Ile Leu Ser Asn Leu Arg Arg Gly Gly Cys Cys Phe His
cct gtc tgt tac atc aat ctt cta gaa atg tgt cgt caa cga ggc
Pro Val Cys Tyr Ile Asn Leu Leu Glu Met Cys Arg Gln Arg Gly
tgatcgtcca ggaccctctg aaccacgacg t
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TABLE 22
DNA Sequence (SEQ ID NO:100) and Protein Sequence (SEQ ID NO:101) of Cn1.1
atg ttc acc gtg ttt ctg ttg gtt gtc ttg aca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser
ttc cct tca gat agt gca tct gat gtc agg gat gac gaa gcc aaa gac
Phe Pro Ser Asp Ser Ala Ser Asp Val Arg Asp Asp Glu Ala Lys Asp
gaa agg tct gac atg tac aaa tcg aaa cgg aat gga cgc tgt tgc cat
Glu Arg Ser Asp Met Tyr Lys Ser Lys Arg Asn Gly Arg Cys Cys His
cct gcc tgt ggc aaa cac ttt agt tgt gga cgc tgatgctcca ggaccctctg
Pro Ala Cys Gly Lys His Phe Ser Cys Gly Arg
aaccacgacg t
TABLE 23
DNA Sequence (SEQ ID NO: 102) and Protein Sequence (SEQ ID NO: 103) of SmI
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
tcc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac gag
Ser Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Glu
aaa gcg tct gac gtg atc gcg ctg gcc ctc aag gga tgc tgt tcc aac
Lys Ala Ser Asp Val Ile Ala Leu Ala Leu Lys Gly Cys Cys Ser Asn
cct gtc tgt cac ctg gag cat tca aac atg tgt ggt aga aga cgc
Pro Val Cys His Leu Glu His Ser Asn Met Cys Gly Arg Arg Arg
tgatgctcca ggaccctctg aaccacgacg
TABLE 24
DNA Sequence (SEQ ID NO:104) and Protein Sequence (SEQ ID NO: 105) of Bt 1. 1
atg ttc tcc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Ser Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
tcc act tca ggt ggt gca tct ggt ggc agg aag get gca gcc aaa gcg
Ser Thr Ser Gly Gly Ala Ser Gly Gly Arg Lys Ala Ala Ala Lys Ala
tct aac cgg atc get ctg acc gtc agg agt gca aca tgc tgt aat tat
Ser Asn Arg Ile Ala Leu Thr Val Arg Ser Ala Thr Cys Cys Asn Tyr
cct ccc tgt tac gag act tat cca gaa agt tgt ctg taacgtgaat
Pro Pro Cys Tyr Glu Thr Tyr Pro Glu Ser Cys Leu
catccagagc tttgtggctg aagacactga tgctccagga ccctctgaac cacgacgt
TABLE 25
DNA Sequence (SEQ ID NO:106) and Protein Sequence (SEQ ID NO:107) of Bt1.2
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtg gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
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ttc act tca ggt cgt gca ttt cgt ggc agg aat cgc gca gcc gac gac
Phe Thr Ser Gly Arg Ala Phe Arg Gly Arg Asn Arg Ala Ala Asp Asp
aaa agg tct gac ctg gcc get ctg agc gtc agg gga gga tgc tgt tcc
Lys Arg Ser Asp Leu Ala Ala Leu Ser Val Arg Gly Gly Cys Cys Ser
cat cct gcc tgt gcg gtg aat cat cca gag ctt tgt ggc tgaagacgct
His Pro Ala Cys Ala Val Asn His Pro Glu Leu Cys Gly
gatgccccag gaccctctga accacgacgt
TABLE 26
DNA Sequence (SEQ ID NO:108) and Protein Sequence (SEQ ID NO:109) of Bt1.3
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca ggt cgt gca tct ggt ggc agg aat get gca gcc aaa gcg
She Thr Ser Gly Arg Ala Ser Gly Gly Arg Asn Ala Ala Ala Lys Ala
tct aac cgg atc get atg gcc atc agc agt gga gca tgc tgt gca tat
Ser Asn Arg Ile Ala Met Ala Ile Ser Ser Gly Ala Cys Cys Ala Tyr
cct ccc tgt ttc gag get tat cca gaa aga tgt ctg taacgtgaat
Pro Pro Cys Phe Glu Ala Tyr Pro Glu Arg Cys Leu
catccagacc tttgtggctg aagacgctga tgccccagga ccctctgaac cacgacgt
TABLE 27
DNA Sequence (SEQ ID NO:110) and Protein Sequence (SEQ ID NO:111) of Bt1.4
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met She Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca gat cgt gca ttt cgt ggc agg aat tcc gca gcc aac gac
Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn Ser Ala Ala Asn Asp
aaa agg tct gac ctg gcc get ctg agc gtc agg aga gga tgc tgc tcc
Lys Arg Ser Asp Leu Ala Ala Leu Ser Val Arg Arg Gly Cys Cys Ser
cat ccc gcc tgt agc gtg aat cat cca gag ctt tgt ggt aga aga cgc
His Pro Ala Cys Ser Val Asn His Pro Glu Leu Cys Gly Arg Arg Arg
tgatgcccca ggaccctctg aaccacgacg t
TABLE 28
DNA Sequence (SEQ ID NO: 112) and Protein Sequence (SEQ ID NO:1 13) of Bt1.5
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met She Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca ggt cgt gca tct ggt ggc agg aat get gca gcc aaa gcg
She Thr Ser Gly Arg Ala Ser Gly Gly Arg Asn Ala Ala Ala Lys Ala
tct aac cgg atc get ctg atc gtc agg aat gca gaa tgc tgt tat tat
Ser Asn Arg Ile Ala Leu Ile Val Arg Asn Ala Glu Cys Cys Tyr Tyr
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cct ccc tgt tac gag get tat cca gaa att tgt ctg taacgtgaat
Pro Pro Cys Tyr Glu Ala Tyr Pro Glu Ile Cys Leu
catccagacc tttgtggctg aagaccctga tgctccagga ccctctgaac cacgacgt
TABLE 29
5 DNA Sequence (SEQ ID NO: 114) and Protein Sequence (SEQ ID NO: 115) of Pn1.1
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc att tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Ile Ser
ttc act tca gat cgt gca tct gat ggc ggg aat gcc gca gcg tct gac
Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Ala Ala Ala Ser Asp
10 ctg atc.gct ctg acc atc aag gga tgc tgt tct cat cct ccc tgt gcc
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Ala
atg aat aat cca gac tat tgt ggt tgacgacgct gatgctccag gaccctctga
Met Asn Asn Pro Asp Tyr Cys Gly
accacgacg
15 TABLE 30
DNA Sequence (SEQ ID NO: 116) and Protein Sequence (SEQ ID NO: 117) of Pn1.2
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca gat cgt gca tct gat ggc ggg aat gcc gca atg tct gac
20 Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Ala Ala Met Ser Asp
ctg atc get ctg acc atc aag gga tgc tgt tct cat cct ccc tgt ttc
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Phe
ctg aat aat cca gac tat tgt ggt tgacgacgct gatgctccag gaccctctga
Leu Asn Asn Pro Asp Tyr Cys Gly
25 accacgacg
TABLE 31
DNA Sequence (SEQ ID NO: 118) and Protein Sequence (SEQ ID NO: 119) of SmI.3
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
30 ttc cct tca gat cgt gaa tct gat ggc gcg aat gac gaa gcc cgc acc
Phe Pro Ser Asp Arg Glu Ser Asp Gly Ala Asn Asp Glu Ala Arg Thr
gac gag cct gag gag cac gga ccg gac agg aat gga tgc tgt agg aat
Asp Glu Pro Glu Glu His Gly Pro Asp Arg Asn Gly Cys Cys Arg Asn
cct gcc tgt gag agc cac aga tgt ggt tgacgacgct gatgctccag
35 Pro Ala Cys Glu Ser His Arg Cys Gly
gaccctctga accacgacg
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TABLE 32
DNA Sequence (SEQ ID NO:120) and Protein Sequence (SEQ ID NO:121) of Cr1.2
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc agc gac
Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Ser Asp
aga gcg tct gac gcg gcc cac cag gga tgc tgt tcc aac cct gtc tgt
Arg Ala Ser Asp Ala Ala His Gln Gly Cys Cys Ser Asn Pro Val Cys
cac gtg gaa cat cca gaa ctt tgt cgt aga aga cgc tgatgctcca
His Val Glu His Pro Glu Leu Cys Arg Arg Arg Arg
ggaccctctg aaccacgacg
TABLE 33
DNA Sequence (SEQ ID NO:122) and Protein Sequence (SEQ ID NO: 123) of CrI.3
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc cct tca aat cgt gaa tct gat ggc gcg aat gcc gaa gtc cgc acc
Phe Pro Ser Asn Arg Glu Ser Asp Gly Ala Asn Ala Glu Val Arg Thr
gac gag cct gag gag cac gac gaa ctg ggc ggg aat gga tgc tgt ggg
Asp Glu Pro Glu Glu His Asp Glu Leu Gly Gly Asn Gly Cys Cys Gly
aat cct gac tgt acg agc cac agt tgt gat tgacgacgct gatgctccag
Asn Pro Asp Cys Thr Ser His Ser Cys Asp
gaccctctga accacgacg
TABLE 34
DNA Sequence (SEQ ID NO:124) and Protein Sequence (SEQ ID NO:125) of EpI
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca gat cgt gca tct gat agc agg aag gac gca gcg tct ggc
Phe Thr Ser Asp Arg Ala Ser Asp Ser Arg Lys Asp Ala Ala Ser Gly
ctg atc get ctg acc atc aag gga tgc tgt tct gat cct cgc tgt aac
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser Asp Pro Arg Cys Asn
atg aat aat cca gac tat tgt ggt tgacgacgct gatgctccag gaccctctga
Met Asn Asn Pro Asp Tyr Cys Gly
accacgacg
TABLE 35
DNA Sequence (SEQ ID NO:126) and Protein Sequence (SEQ ID NO:127) of Sn1.1
atg tcc acc gtg ttt ctg ttg gtt gtc ctc gca acc acc gtc gtt tcc
Met Ser Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
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ttc act gta gat cgt gca tct gat ggc agg gat gtc gca atc gac gac
Phe Thr Val Asp Arg Ala Ser Asp Gly Arg Asp Val Ala Ile Asp Asp
aga ttg gtg tct ctc cct cag atc gcc cat get gac tgt tgt tcc gat
Arg Leu Val Ser Leu Pro Gln Ile Ala His Ala Asp Cys Cys Ser Asp
cct gcc tgc aag cag acg ccc ggt tgt cgt taaagacgct gctgctccag
Pro Ala Cys Lys Gln Thr Pro Gly Cys Arg
gaccctctga accacgacg
TABLE 36
DNA Sequence (SEQ ID NO:128) and Protein Sequence (SEQ ID NO:129) of Snl.2
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc get tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Ala Ser
ttc att atc gat gat cca tct gat ggc agg aat att gca gtc gac gac
Phe Ile Ile Asp Asp Pro Ser Asp Gly Arg Asn Ile Ala Val Asp Asp
aga ggg ctt ttc tct acg ctc ttc cat get gat tgc tgt gaa aat cct
Arg Gly Leu Phe Ser Thr Leu Phe His Ala Asp Cys Cys Glu Asn Pro
gcc tgt aga cac acg cag ggt tgt tgatctttgt tcttcaaaga cactgctggc
Ala Cys Arg His Thr Gln Gly Cys
ccaggaccct ctgaaccacg acg
TABLE 37
DNA Sequence (SEQ ID NO:130) and Protein Sequence (SEQ ID NO:131) of Dal.1
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca gat cgt gca ttt cgt ggc agg aat gcc gca gcc aaa gag
Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys Glu
tct ggc ctg gtc ggt ctg acc gac aag acg cga gga tgc tgt tct cat
Ser Gly Leu Val Gly Leu Thr Asp Lys Thr Arg Gly Cys Cys Ser His
cct gcc tgt aac gta gat cat cca gaa att tgt ggt tgaagacgct
Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Gly
gatgctccag gaccctctga accacgacgt
TABLE 38
DNA Sequence (SEQ ID NO:132) and Protein Sequence (SEQ ID NO:133) of Dal.2
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca gat ggt gca tct gat gac agg aaa gcc get gcg tct gac
Phe Thr Ser Asp Gly Ala Ser Asp Asp Arg Lys Ala Ala Ala Ser Asp
ctg atc act ctg acc atc aag gga tgc tgt tct cgt cct ccc tgt atc
Leu Ile Thr Leu Thr Ile Lys Gly Cys Cys Ser Arg Pro Pro Cys Ile
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gcg aat aat cca gac ttg tgt ggt cga cga cgc tgatgctcca ggaccctctg
Ala Asn Asn Pro Asp Leu Cys Gly Arg Arg Arg
TABLE 39
DNA Sequence (SEQ ID NO:134) and Protein Sequence (SEQ ID NO:135) of Dal.3
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
tcc act tca ggt cgt cgt gca ttt cat ggc agg aat gcc gca gcc aaa
Ser Thr Ser Gly Arg Arg Ala Phe His Gly Arg Asn Ala Ala Ala Lys
gcg tct gga ctg gtc ggt ctg act gac agg aga cca caa tgc tgt agt
Ala Ser Gly Leu Val Gly Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser
gat cct cgc tgt aac gta ggt cat cca gaa ctt tgt ggt gga aga cgc
Asp Pro Arg Cys Asn Val Gly His Pro Glu Leu Cys Gly Gly Arg Arg
tgatgctcca ggaccctctg aaccacaacg t
TABLE 40
DNA Sequence (SEQ ID NO:136) and Protein Sequence (SEQ ID NO:137) of Dal.4
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
tcc act tca ggt cgt gca ttt cat ggc agg aat gcc gca gcc aaa gcg
Ser Thr Ser Gly Arg Ala Phe His Gly Arg Asn Ala Ala Ala Lys Ala
tct ggc ctg gtc ggt ctg acc gac aag agg caa gta tgc tgt agt gat
Ser Gly Leu Val Gly Leu Thr Asp Lys Arg Gln Val Cys Cys Her Asp
cct cgc tgt aac gta ggt cat cca gaa att tgt ggt gga aga cgc
Pro Arg Cys Asn Val Gly His Pro Glu Ile Cys Gly Gly Arg Arg
tgatgctcca ggaccctctg aaccacgacg t
TABLE 41
DNA Sequence (SEQ ID NO:138) and Protein Sequence (SEQ ID NO:139) of A1.2
atg ttc acc gtg ttt ctg ttg gtt gtc ttg aca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser
ttc cct tca gat agt gca tct ggt ggc agg gat gac gag gcc aaa gac
Phe Pro Ser Asp Ser Ala Ser Gly Gly Arg Asp Asp Glu Ala Lys Asp
gaa agg tct gac atg tac gaa ttg aaa cgg aat gga cgc tgt tgc cat
Glu Arg Ser Asp Met Tyr Glu Leu Lys Arg Asn Gly Arg Cys Cys His
cct gcc tgt ggt ggc aaa tac gtt aaa tgt gga cgc tgatgctcca
Pro Ala Cys Gly Gly Lys Tyr Val Lys Cys Gly Arg
ggaccctctc gaaccacg
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TABLE 42
DNA Sequence (SEQ ID NO:140) and Protein Sequence (SEQ ID NO:141) of Bul.1
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc tct aca gat gat gaa tct gat ggc tcg aat gaa gaa ccc agc gcc
Phe Ser Thr Asp Asp Glu Ser Asp Gly Ser Asn Glu Glu Pro Ser Ala
gac cag act gcc agg tcc tca atg aac agg gcg cct gga tgc tgt aac
Asp Gln Thr Ala Arg Ser Ser Met Asn Arg Ala Pro Gly.Cys Cys Asn
aat cct gcc tgt gtg aag cac aga tgt gga tgacgctgat gctccaggac
Asn Pro Ala Cys Val Lys His Arg Cys Gly
cctctgaacc acgacgt
TABLE 43
DNA Sequence (SEQ ID NO:142) and Protein Sequence (SEQ ID NO:143) of Bul.2
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc tct aca gat gat gaa tct gat ggc tcg aat gaa gaa ccc agc gcc
Phe Ser Thr Asp Asp Glu Ser Asp Gly Ser Asn Glu Glu Pro Ser Ala
gac cag get gcc agg tcc gca atg aac agg ccg cct gga tgc tgt aac
Asp Gln Ala Ala Arg Ser Ala Met Asn Arg Pro Pro Gly Cys Cys Asn
aat cct gcc tgt gtg aag cac aga tgt ggt gga tgacgctgat gctccaggac
Asn Pro Ala Cys Val Lys His Arg Cys Gly Gly
cctctgaacc acgacgt
TABLE 44
DNA Sequence (SEQ ID NO:144) and Protein Sequence (SEQ ID NO:145) of Bul.3
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc cct tca gat cgt gac tct gat ggc gcg gat gcc gaa gcc agt gac
Phe Pro Ser Asp Arg Asp Ser Asp Gly Ala Asp Ala Glu Ala Ser Asp
gag cct gtt gag ttc gaa agg gac gag aat gga tgc tgt tgg aat cct
Glu Pro Val Glu Phe Glu Arg Asp Glu Asn Gly Cys Cys Trp Asn Pro
tcc tgt ccg agg ccc aga tgt aca gga cga cgc taatgctcca ggaccctctg
Ser Cys Pro Arg Pro Arg Cys Thr Gly Arg Arg
aaccacgacg t
TABLE 45
DNA Sequence (SEQ ID NO:146) and Protein Sequence (SEQ ID NO:170) of Bul.4
atg ttc acc gtg ttt ctg ttg gtt gtc ttg aca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser
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ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac gac
Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp
aaa gcg tct gac gtg gtc acg ctg gtc ctc aag gga tgc tgt tcc acc
Lys Ala Ser Asp Val Val Thr Leu Val Leu Lys Gly Cys Cys Ser Thr
5 cct ccc tgt get gtg ctg tat tgt ggt aga aga cgc tgatgctcca
Pro Pro Cys Ala Val Leu Tyr Cys Gly Arg Arg Arg
ggaccctctg aaccacgacg t
TABLE 46
DNA Sequence (SEQ ID NO:148) and Protein Sequence (SEQ ID NO: 149) of Di 1. 1
10 atg ttc acc gtg ttt ctg ttg gtt gtc ttc gca tcc tct gtc acc tta
Met Phe Thr Val Phe Leu Leu Val Val Phe Ala Ser Ser Val Thr Leu
gat cgt gca tct tat ggc agg tat gcc tca ccc gtc gac aga gcg tct
Asp Arg Ala Ser Tyr Gly Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser
gcc ctg atc get cag gcc atc ctt cga gat tgc tgc tcc aat cct cct
15 Ala Leu Ile Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro
tgt gcc cat aat aat cca gac tgt cgt taaagacgct gcttgctcca
Cys Ala His Asn Asn Pro Asp Cys Arg
ggaccctctg aaccacgacg t
TABLE 47
20 DNA Sequence (SEQ ID NO:150) and Protein Sequence (SEQ ID NO:151) of Ti
gga tgc tgt tct aat cct ccc tgt atc gcg aag aat cca cac atg tgt
Gly Cys Cys Ser Asn Pro Pro Cys Ile Ala Lys Asn Pro His Met Cys
ggt gga aga cgc tga
Gly Gly Arg Arg
25 TABLE 48
DNA Sequence (SEQ ID NO:152) and Protein Sequence (SEQ ID NO:153) of Cn1.2
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac gac
30 Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp
aaa gcg tct gac gtg atc acg ctg gcc ctc aag gga tgc tgt tcc aac
Lys Ala Ser Asp Val Ile Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn
cct gtc tgt cac ttg gag cat tca aac ctt tgt ggt aga aga cgc
Pro Val Cys His Leu Glu His Ser Asn Leu Cys Gly Arg Arg Arg
35 tgatgctcca ggaccctctg aaccacgacg t
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TABLE 49
DNA Sequence (SEQ ID NO:233) and Protein Sequence (SEQ ID NO:234) of Iml.1
tct gat gga aag agt gcc gcg gcc aaa gcc aaa ccg tct cac ctg acg
Ser Asp Gly Lys Ser Ala Ala Ala Lys Ala Lys Pro Ser His Leu Thr
get cca ttc atc agg gac gaa tgc tgt tcc gat tct cgc tgt ggc aag
Ala Pro Phe Ile Arg Asp Glu Cys Cys Ser Asp Ser Arg Cys Gly Lys
aac tgt ctt tga
Asn Cys Leu
TABLE 50
DNA Sequence (SEQ ID NO:235) and Protein Sequence (SEQ ID NO:236) of Iml.2
ttt gat gga agg aat gcc cca gcc gac gac aaa gcg tct gac ctg atc
Phe Asp Gly Arg Asn Ala Pro Ala Asp Asp Lys Ala Ser Asp Leu Ile
get caa atc gtc agg aga gca tgc tgt tcc gat cgt cgc tgt aga tgg
Ala Gln Ile Val Arg Arg Ala Cys Cys Ser Asp Arg Arg Cys Arg Trp
agg tgt ggt tga
Arg Cys Gly
TABLE 51
DNA Sequence (SEQ ID NO:237) and Protein Sequence (SEQ ID NO:238) of Rg1.2
tct gat gga agg aat gcc gca gcc gac gcc aga gcg tct ccc cgg atc
Ser Asp Gly Arg Asn Ala Ala Ala Asp Ala Arg Ala Ser Pro Arg Ile
get ctt ttc ctc agg ttc aca tgc tgt agg aga ggt acc tgt tcc cag
Ala Leu Phe Leu Arg Phe Thr Cys Cys Arg Arg Gly Thr Cys Ser Gln
cac tgt ggt tgaagacact gctgctccag gaccctctga accacgacgt
His Cys Gly
TABLE 52
DNA Sequence (SEQ ID NO:239) and Protein Sequence (SEQ ID NO:240) of Rg 1.6
tct aat gga agg aat gcc gca gcc gac gcc aaa gcg tct caa cgg atc
Ser Asn Gly Arg Asn Ala Ala Ala Asp Ala Lys Ala Ser Gln Arg Ile
get cca ttc ctc agg gac tat tgc tgt agg aga cat gcc tgt acg ttg
Ala Pro Phe Leu Arg Asp Tyr Cys Cys Arg Arg His Ala Cys Thr Leu
att tgt ggt tgaagacgct gctgctccag gaccctctga accacgacgt
Ile Cys Gly
TABLE 53
DNA Sequence (SEQ ID NO:241) and Protein Sequence (SEQ ID NO:242) of Rgl.6A
tct aat gga agg aat gcc gca gcc gac gcc aaa gcg tct caa cgg atc
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Ser Asn Gly Arg Asn Ala Ala Ala Asp Ala Lys Ala Ser Gln Arg Ile
get cca ttc ctc agg gac tat tgc tgt agg aga cct ccc tgt acg ttg
Ala Pro Phe Leu Arg Asp Tyr Cys Cys Arg Arg Pro Pro Cys Thr Leu
att tgt ggt tgaagacgct gctgctccag gaccctctga accacgacgt
Ile Cys Gly
TABLE 54
DNA Sequence (SEQ ID NO:243) and Protein Sequence (SEQ ID NO:244) of Rg1.7
tct aat aaa agg aag aat gcc gca atg ctt gac atg atc get caa cac
Ser Asn Lys Arg Lys Asn Ala Ala Met Leu Asp Met Ile Ala Gln His
gcc ata agg ggt tgc tgt tcc gat cct cgc tgt aga tat aga tgt cgt
Ala Ile Arg Gly Cys Cys Ser Asp Pro Arg Cys Arg Tyr Arg Cys Arg
tgaagacgct gctgctccag gaccctctga accacgacgt
TABLE 55
DNA Sequence (SEQ ID NO:245) and Protein Sequence (SEQ ID NO:246) of Rg1.9
ttt aat gga agg agt gcc gca gcc gac caa aat gcg cct ggc ctg atc
Phe Asn Gly Arg Ser Ala Ala Ala Asp Gln Asn Ala Pro Gly Leu Ile
get caa gtc gtc aga gga ggg tgc tgt tcc gat ccc cgc tgc gcc tgg
Ala Gln Val Val Arg Gly Gly Cys Cys Ser Asp Pro Arg Cys Ala Trp
aga tgt ggt tgaagacgtt gctgctccag gaccctctga accacgacgt
Arg Cys Gly
TABLE 56
DNA Sequence (SEQ ID NO:247) and Protein Sequence (SEQ ID NO:248) of Rg1.10
ttt gat gga agg aat gcc gca gcc gac gcc aaa gtg att aac acg gtc
Phe Asp Gly Arg Asn Ala Ala Ala Asp Ala Lys Val Ile Asn Thr Val
get cga atc gcc tgg gat ata tgc tgt tcc gaa cct gac tgt aac cat
Ala Arg Ile Ala Trp Asp Ile Cys Cys Ser Glu Pro Asp Cys Asn His
aaa tgt gtt tgaagacgct tctgctccag gaccctctga accacgacgt
Lys Cys Val
TABLE 57
DNA Sequence (SEQ ID NO:249) and Protein Sequence (SEQ ID NO:250) of Rg1.11
tct aat aaa agg aag aat gcc gca atg ctt gac atg atc get caa cac
Ser Asn Lys Arg Lys Asn Ala Ala Met Leu Asp Met Ile Ala Gln His
gcc ata agg ggt tgc tgt tcc gat cct cgc tgt aaa cat cag tgt ggt
Ala Ile Arg Gly Cys Cys Ser Asp Pro Arg Cys Lys His Gln Cys Gly
tgaagacgct gctgctccag gaccctctga accacgacgt
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TABLE 58
DNA Sequence (SEQ ID NO:251) and Protein Sequence (SEQ ID NO:252) of Msl .7
atc aag aat aca gca gcc agc aac aaa gcg tct agc ctg gtg get ctt
Ile Lys Asn Thr Ala Ala Ser Asn Lys Ala Ser Ser Leu Val Ala Leu
gtt gtc agg gga tgc tgt tac aat cct gtc tgc aag aaa tat tat tgt
Val Val Arg Gly Cys Cys Tyr Asn Pro Val Cys Lys Lys Tyr Tyr Cys
tgg aaa ggc tgatgctcca ggaccctctg aaccacgacg t
Trp Lys Gly
TABLE 59
DNA Sequence (SEQ ID NO:253) and Protein Sequence (SEQ ID NO:254) of P1.7
tct gaa ggc agg aat get gaa gcc atc gac aac gcc tta gac cag agg
Ser Glu Gly Arg Asn Ala Glu Ala Ile Asp Asn Ala Leu Asp Gln Arg
gat cca aag cga cag gag ccg ggg tgc tgt agg cat cct gcc tgt ggg
Asp Pro Lys Arg Gln Glu Pro Gly Cys Cys Arg His Pro Ala Cys Gly
aag aac aga tgt gga aga cgc tgatgctcca ggaccctctg aaccacgacg t
Lys Asn Arg Cys Gly Arg Arg
TABLE 60
DNA Sequence (SEQ ID NO:255) and Protein Sequence (SEQ ID NO:256) of Ms1.2
tct gat ggc agg aat att gca gtc gac gac aga tgg tct ttc tat acg
Ser Asp Gly Arg Asn Ile Ala Val Asp Asp Arg Trp Ser Phe Tyr Thr
ctc ttc cat get act tgc tgt gcc gat cct gac tgt aga ttc cgg ccc
Leu Phe His Ala Thr Cys Cys Ala Asp Pro Asp Cys Arg Phe Arg Pro
ggt tgt tgatctttgt tcttcaaaga cgctgctggc ccaggaccct ctgaaccacg
Gly Cys
acgt
TABLE 61
DNA Sequence (SEQ ID NO:257) and Protein Sequence (SEQ ID NO:258) of Ms1.3
atc aag aat act gca gcc agc aac aaa gcg cct agc ctg gtg get att
Ile Lys Asn Thr Ala Ala Ser Asn Lys Ala Pro Ser Leu Val Ala Ile
gcc gtc agg gga tgc tgt tac aat cct tcc tgt tgg ccg aaa aca tat
Ala Val Arg Gly Cys Cys Tyr Asn Pro Ser Cys Trp Pro Lys Thr Tyr
tgt agt tggaaaggct gatgctccag gaccctctga accacgacgt
Cys Ser
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TABLE 62
DNA Sequence (SEQ ID NO:259) and Protein Sequence (SEQ ID NO:260) of Ms1.4
tct gat agc agg aat gtc gca atc gag gac aga gtg tct gac ctg cac
Ser Asp Ser Arg Asn Val Ala Ile Glu Asp Arg Val Ser Asp Leu His
tct atg ttc ttc gat gtt tct tgc tgt agc aat cct acc tgt aaa gaa
Ser Met Phe Phe Asp Val Ser Cys Cys Ser Asn Pro Thr Cys Lys Glu
acg tat ggt tgt tgatcgttgg ttttgaagac gctgatgctc caggaccctc
Thr Tyr Gly Cys
TABLE 63
DNA Sequence (SEQ ID NO:261) and Protein Sequence (SEQ ID NO:262) of Ms1.5
tct gtt ggc agg aat att gca gtc gac gac aga ggg att ttc tct acg
Ser Val Gly Arg Asn Ile Ala Val Asp Asp Arg Gly Ile Phe Ser Thr
ctc ttc cat get cat tgc tgt gcc aat ccc atc tgt aaa aac acg ccc
Leu Phe His Ala His Cys Cys Ala Asn Pro Ile Cys Lys Asn Thr Pro
ggt tgt tgatctttgt tcttcaaaga cgctgctggc ccaggaccct ctgaaccacg
Gly Cys
acgt
TABLE 64
DNA Sequence (SEQ ID NO:263) and Protein Sequence (SEQ ID NO:264) of Ms1.8
tcc gat ggc agg aat gtc gca atc gac gac aga gtg tct gac ctg cac
Ser Asp Gly Arg Asn Val Ala Ile Asp Asp Arg Val Ser Asp Leu His
tct atg ttc ttc gat att get tgc tgt aac aat cct acc tgt aaa gaa
Ser Met Phe Phe Asp Ile Ala Cys Cys Asn Asn Pro Thr Cys Lys Glu
acg tat ggt tgt tgatcgttgg ttttgaagac gctgatgctc caggaccctc
Thr Tyr Gly Cys
tgaaccacga cgt
TABLE 65
DNA Sequence (SEQ ID NO:265) and Protein Sequence (SEQ ID NO:266) of Ms1.9
tct gat ggc agg aat gtc gca atc gag gac aga gtg tct gac ctg ctc
Ser Asp Gly Arg Asn Val Ala Ile Glu Asp Arg Val Ser Asp Leu Leu
tct atg ctc ttc gat gtt get tgc tgt agc aat cct gtc tgt aaa gaa
Ser Met Leu Phe Asp Val Ala Cys Cys Ser Asn Pro Val Cys Lys Glu
acg tat ggt tgt tgatcgttgg ttttgaagac gctgatgctc caggaccctc
Thr Tyr Gly Cys
tgaaccacga cgt
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TABLE 66
DNA Sequence (SEQ ID NO:267) and Protein Sequence (SEQ ID NO:268) of Bt1.7
tat gat ggc agg aat get gcc gcc gac gac aaa get ttt gac ctg ctg
Tyr Asp Gly Arg Asn Ala Ala Ala Asp Asp Lys Ala Phe Asp Leu Leu
5 get atg acc ata agg gga gga tgc tgt tcc tat cct ccc tgt atc gcg
Ala Met Thr Ile Arg Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala
agt aat cct aaa tgt ggt gga aga cgc tgatgctcca ggaccctctg
Ser Asn Pro Lys Cys Gly Gly Arg Arg
aaccacaacg t
10 TABLE 67
DNA Sequence (SEQ ID NO:269) and Protein Sequence (SEQ ID NO:270) of Lv1.5
ttt gat ggc agg aat get gca ggc aac gcc aaa atg tcc gcc ctg atg
Phe Asp Gly Arg Asn Ala Ala Gly Asn Ala Lys Met Ser Ala Leu Met
gcc ctg acc atc agg gga tgc tgt tcc cat cct gtc tgt agc gcg atg
15 Ala Leu Thr Ile Arg Gly Cys Cys Ser His Pro Val Cys Ser Ala Met
agt cca atc tgt ggc tgaagacgct gatgccccag gaccctctga accacgacgt
Ser Pro Ile Cys Gly
TABLE 68
DNA Sequence (SEQ ID NO:271) and Protein Sequence (SEQ ID NO:272) of Ms1.10
20 atc aag aat get gca get gac gac aaa gca tct gac ctg ctc tct cag
Ile Lys Asn Ala Ala Ala Asp Asp Lys Ala Ser Asp Leu Leu Ser Gln
atc gtc agg aat get gca tcc aat gac aaa ggg tct gac ctg atg act
Ile Val Arg Asn Ala Ala Ser Asn Asp Lys Gly Ser Asp Leu Met Thr
ctt gcc ctc agg gga tgc tgt aaa aat cct tac t.gt ggt gcg tcg aaa
25 Leu Ala Leu Arg Gly Cys Cys Lys Asn Pro Tyr Cys Gly Ala Ser Lys
aca tat tgt ggt aga aga cgc tgatgctcca ggaccctctg aaccacgacg t
Thr Tyr Cys Gly Arg Arg Arg
TABLE 69
DNA Sequence (SEQ ID NO:273) and Protein Sequence (SEQ ID NO:274) of Oml.l
30 tctgatggca ggaatgccgc agcgtctgac ctgatggat ctg acc atc aag gga
Leu Thr Ile Lys Gly
tgc tgt tct tat cct ccc tgt ttc gcg act aat cca gac tgt ggt cga
Cys Cys Ser Tyr Pro Pro Cys Phe Ala Thr Asn Pro Asp Cys Gly Arg
cga cgc tgatgctcca ggaccctctg aaccacgacg t
35 Arg Arg
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TABLE 70
DNA Sequence (SEQ ID NO:275) and Protein Sequence (SEQ ID NO:276) of R1.6
ttt gat ggc agg aat gcc gca gcc gac tac aaa ggg tct gaa ttg ctc
Phe Asp Gly Arg Asn Ala Ala Ala Asp Tyr Lys Gly Ser Glu Leu Leu
get atg acc gtc agg gga gga tgc tgt tcc tat cct ccc tgt atc gca
Ala Met Thr Val Arg Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala
aat aat cct ctt tgt get gga aga cgc tga
Asn Asn Pro Leu Cys Ala Gly Arg Arg
TABLE 71
DNA Sequence (SEQ ID NO:277) and Protein Sequence (SEQ ID NO:278) of R1.7
ttt gat ggc agg aat gcc gca gcc gac tac aaa ggg tct gaa ttg ctc
Phe Asp Gly Arg Asn Ala Ala Ala Asp Tyr Lys Gly Ser Glu Leu Leu
get atg acc gtc agg gga gga tgc tgt tcc tat cct ccc tgt atc gca
Ala Met Thr Val Arg Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala
aat aat cct ttt tgt get gga aga cgc tga
Asn Asn Pro Phe Cys Ala Gly Arg Arg
TABLE 72
DNA Sequence (SEQ ID NO:279) and Protein Sequence (SEQ ID NO:280) of Vrl.I
tct tat gac agg tat gcc tcg ccc gtc gac aga gcg tct gcc ctg atc
Ser Tyr Asp Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser Ala Leu Ile
get cag gcc atc ctt cga gat tgc tgt tcc aat cct ccc tgt tcc caa
Ala Gln Ala Ile'Leu Arg Asp Cys Cys Ser Asn Pro Pro Cys Ser Gln
aat aat cca gac tgt atg taaagacgct gcttgctcca ggaccctctg
Asn Asn Pro Asp Cys Met
aaccacgacg t
TABLE 73
DNA Sequence (SEQ ID NO:281) and Protein Sequence (SEQ ID NO:282) of Vrl.2
tct tat ggc agg tat gcc tca ccc gtc gac aga gcg tct gcc ctg atc
Ser Tyr Gly Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser Ala Leu Ile
get cag gcc atc ctt cga gat tgc tgc tcc aat cct cct tgt gcc cat
Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro Cys Ala His
aat aat cca gac tgt cgt taaagacgct gcttgctcca ggaccctctg
Asn Asn Pro Asp Cys Arg
aaccacgacg t
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TABLE 74
DNA Sequence (SEQ ID NO:283) and Protein Sequence (SEQ ID NO:284) of A1.4
tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct ggc atg agc
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Gly Met Ser
gcg ctg gcc gtc aat gaa tgc tgt acc aac cct gtc tgt cac gcg gaa
Ala Leu Ala Val Asn Glu Cys Cys Thr Asn Pro Val Cys His Ala Glu
cat caa gaa ctt tgt get aga aga cgc tga
His Gln Glu Leu Cys Ala Arg Arg Arg
TABLE 75
DNA Sequence (SEQ ID NO:285) and Protein Sequence (SEQ ID NO:286) of A1.5
tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct gac gtg atc
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Val Ile
acg ctg gcc ctc aag gga tgc tgt tcc aac cct gtc tgt cac ttg gag
Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn Pro Val Cys His Leu Glu
cat tca aac ctt tgt ggt aga aga cgc tga
His Ser Asn Leu Cys Gly Arg Arg Arg
TABLE 76
DNA Sequence (SEQ ID NO:287) and Protein Sequence (SEQ ID NO:288) of A1.6
tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct ggc atg agc
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Gly Met Ser
gcg ctg gcc gtc aat gaa tgc tgt acc aac cct gtc tgt cac gtg gaa
Ala Leu Ala Val Asn Glu Cys Cys Thr Asn Pro Val Cys His Val Glu
cat caa gaa ctt tgt get aga aga cgc tga
His Gln Glu Leu Cys Ala Arg Arg Arg
TABLE 77
DNA Sequence (SEQ ID NO:289) and Protein Sequence (SEQ ID NO:290) of Afl.l
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca gat cgt gca ttt cgt ggc agg aat gcc gca gcc aaa gcg
Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys Ala
tct ggc ctg gtc ggt ctg acc gac aag agg caa gaa tgc tgt tct tat
Ser Gly Leu Val Gly Leu Thr Asp Lys Arg Gln Glu Cys Cys Ser Tyr
cct gcc tgt aac cta gat cat cca gaa ctt tgt ggt tgaagacgct
Pro Ala Cys Asn Leu Asp His Pro Glu Leu Cys Gly
gatgctccag gaccctctga accacgacgt
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TABLE 78
DNA Sequence (SEQ ID NO:291) and Protein Sequence (SEQ ID NO:292) of Afl.2
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
tcc act tca ggt cgt cgt gca ttt cgt ggc agg aat gcc gca gcc aaa
Ser Thr Ser Gly Arg Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys
gcg tct gga ctg gtc ggt ctg act gac agg aga cca gaa tgc tgt agt
Ala Ser Gly Leu Val Gly Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser
gat cct cgc tgt aac tcg act cat cca gaa ctt tgt ggt gga aga cgc
Asp Pro Arg Cys Asn Ser Thr His Pro Glu Leu Cys Gly Gly Arg Arg
tgatgctcca ggaccctctg aaccacgacg t
TABLE 79
DNA Sequence (SEQ ID NO:293) and Protein Sequence (SEQ ID NO:294) of Arl.2
tct gat ggc agg aat gcc gca gcc aac gcg ttt gac ctg atc gat ctg
Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Phe Asp Leu Ile Asp Leu
acc gcc agg cta aat tgc tgt atg att ccc ccc tgt tgg aag aaa tat
Thr Ala Arg Leu Asn Cys Cys Met Ile Pro Pro Cys Trp Lys Lys Tyr
gga gac aga tgt agt gaa gta cgc tgatgctcca ggaccctctg aaccacgacg
Gly Asp Arg Cys Ser Glu Val Arg
t
TABLE 80
DNA Sequence (SEQ ID NO:295) and Protein Sequence (SEQ ID NO:296) of Arl.3
tct gat ggc agg aat gcc gca cgc aaa gcg ttt ggc tgc tgc gac tta
Ser Asp Gly Arg Asn Ala Ala Arg Lys Ala Phe Gly Cys Cys Asp Leu
ata ccc tgt ttg gag aga tat ggt aac aga tgt aat gaa gtg cac
Ile Pro Cys Leu Glu Arg Tyr Gly Asn Arg Cys Asn Glu Val His
tgatgctcca ggaccctctg aaccacgcga cgt
TABLE 81
DNA Sequence (SEQ ID NO:297) and Protein Sequence (SEQ ID NO:298) of Arl.4
tct gat ggc agc aat gcc gca gcc aac gag ttt gac ctg atc get ctg
Ser Asp Gly Ser Asn Ala Ala Ala Asn Glu Phe Asp Leu Ile Ala Leu
acc gcc agg cta ggt tgc tgt aac gtt aca ccc tgt tgg gag aaa tat
Thr Ala Arg Leu Gly Cys Cys Asn Val Thr Pro Cys Trp Glu Lys Tyr
gga gac aaa tgt aat gaa gta cgc tgatgcttca ggaccctctg aaccacgacg
Gly Asp Lys Cys Asn Glu Val Arg
t
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TABLE 82
DNA Sequence (SEQ ID NO:299) and Protein Sequence (SEQ ID NO:300) of Arl.5
tct gat ggc agg aat gtc gca gca aaa gcg ttt cac cgg atc ggc cgg
Ser Asp Gly Arg Asn Val Ala Ala Lys Ala Phe His Arg Ile Gly Arg
acc atc agg gat gaa tgc tgt tcc aat cct gcc tgt agg gtg aat aat
Thr Ile Arg Asp Glu Cys Cys Ser Asn Pro Ala Cys Arg Val Asn Asn
cca cac gtt tgt aga cga cgc tgatgctcca ggaccctctg aaccacgacg t
Pro His Val Cys Arg Arg Arg
TABLE 83
DNA Sequence (SEQ ID NO:301) and Protein Sequence (SEQ ID NO:302) of Arl.6
tct gat ggc agg aat gcc gca gcc aac gcg ttt gac ctg atg cct ctg
Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Phe Asp Leu Met Pro Leu
acc gcc agg cta aat tgc tgt agc att ccc ggc tgt tgg aac gaa tat
Thr Ala Arg Leu Asn Cys Cys Ser Ile Pro Gly Cys Trp Asn Glu Tyr
aaa gac aga tgt agt aaa gta cgc tgatgctcca ggaccctctg aaccacgacg
Lys Asp Arg Cys Ser Lys Val Arg
t
TABLE 84
DNA Sequence (SEQ ID NO:303) and Protein Sequence (SEQ ID NO:304) of Ayl.2
tctgatggca ggaatgccgc agccgacgac aaagcgtctg acctggtcgc t ctg gtc
Leu Val
gtc agg gga gga tgc tgt tcc cac cct gtc tgt tac ttt aat aat cca
Val Arg Gly Gly Cys Cys Ser His Pro Val Cys Tyr Phe Asn Asn Pro
caa atg tgt cgt gga aga cgc tgatgctcca ggaccctctg aaccacgacg t
Gln Met Cys Arg Gly Arg Arg
TABLE 85
DNA Sequence (SEQ ID NO:305) and Protein Sequence (SEQ ID NO:306) of Ayl.3
tctgatggca ggaatgccgc agccgacgac aaagcgtctg acctggtcgc t ctg gcc
Leu Ala
gtc agg gga gga tgc tgt tcc cac cct gtc tgt aac ttg aat aat cca
Val Arg Gly Gly Cys Cys Ser His Pro Val Cys Asn Leu Asn Asn Pro
caa atg tgt cgt gga aga cgc tgatgctcca ggaccctctg aaccacgacg t
Gln Met Cys Arg Gly Arg Arg
TABLE 86
DNA Sequence (SEQ ID NO:307) and Protein Sequence (SEQ ID NO:308) of Btl.8
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ttt cgt ggc agg aat ccc gca gcc aac gac aaa agg tct gac ctg gcc
Phe Arg Gly Arg Asn Pro Ala Ala Asn Asp Lys Arg Ser Asp Leu Ala
get ctg agc gtc agg gga gga tgc tgt tcc cat cct gcc tgt agc gtg
Ala Leu Ser Val Arg Gly Gly Cys Cys Ser His Pro Ala Cys Ser Val
5 act cat cca gag ctt tgt ggc tgaagacgct gatgccccag gaccctctga
Thr His Pro Glu Leu Cys Gly
accacgacgt
TABLE 87
DNA Sequence (SEQ ID NO:309) and Protein Sequence (SEQ ID NO:310) of Bt1.9
10 tct gat ggc ggg aat gcc gca gcc aaa gcg tct gac ctg atc get cag
Ser Asp Gly Gly Asn Ala Ala Ala Lys Ala Ser Asp Leu Ile Ala Gln
acc atc agg gga gga tgc tgt tcc tat cct gcc tgt agc gtg gaa cat
Thr Ile Arg Gly Gly Cys Cys Ser Tyr Pro Ala Cys Ser Val Glu His
caa gac ctt tgt gat gga aga cgc tgatgctcca ggaccctctg aaccacgacg
15 Gln Asp Leu Cys Asp Gly Arg Arg
t
TABLE 88
DNA Sequence (SEQ ID NO:31 1) and Protein Sequence (SEQ ID NO:312) of Cal.3
tct tat ggc agg aat gcc gca gcc aaa gcg ttt gaa gtg agt tgc tgt
20 Ser Tyr Gly Arg Asn Ala Ala Ala Lys Ala Phe Glu Val Ser Cys Cys
gtc gtt cgc ccc tgt tgg att cgc tat caa gag gaa tgt ctt gaa gca
Val Val Arg Pro Cys Trp Ile Arg Tyr Gln Glu Glu Cys Leu Glu Ala
gat ccc agg acc ctc tga
Asp Pro Arg Thr Leu
25 TABLE 89
DNA Sequence (SEQ ID NO:313) and Protein Sequence (SEQ ID NO:314) of Cal.4
tct gat ggc agg aat gcc gca gcc aac gcc ctt gac ctg atc act ctg
Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Leu Asp Leu Ile Thr Leu
atc gcc agg caa aat tgc tgt agc att ccc ggc tgt tgg gag aaa tat
30 Ile Ala Arg Gln Asn Cys Cys Ser Ile Pro Gly Cys Trp Glu Lys Tyr
gga gac aaa tgt agt gaa gta cgc tga
Gly Asp Lys Cys Ser Glu Val Arg
TABLE 90
DNA Sequence (SEQ ID NO:315) and Protein Sequence (SEQ ID NO:316) of C1.2
35 tct gat ggc agg aat gaa gca gcc aac gac gaa gcg tct gac gtg atc
Ser Asp Gly Arg Asn Glu Ala Ala Asn Asp Glu Ala Ser Asp Val Ile
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gag ctg gcc ctc aag gga tgc tgt tcc aac cct gtc tgt cac ttg gag
Glu Leu Ala Leu Lys Gly Cys Cys Ser Asn Pro Val Cys His Leu Glu
cat cca aac get tgt ggt aga aga cgc tgatgctcca ggaccctctg
His Pro Asn Ala Cys Gly Arg Arg Arg
aaccacgacg t
TABLE 91
DNA Sequence (SEQ ID NO:317) and Protein Sequence (SEQ ID NO:318) of C1.3
tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct gac ctg gtc
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Val
get ctg gcc gtc agg gga tgc tgt tcc aac cct atc tgt tac ttt aat
Ala Leu Ala Val Arg Gly Cys Cys Ser Asn Pro Ile Cys Tyr Phe Asn
aat cca cga att tgt cgt gga aga cgc tgatgctcca ggaccctctg
Asn Pro Arg Ile Cys Arg Gly Arg Arg
aaccacgacg t
TABLE 92
DNA Sequence (SEQ ID NO:319) and Protein Sequence (SEQ ID NO:320) of Epl.2
tct cat ggc agg aat gcc gca cgc aaa gcg tct gac ctg atc get ctg
Ser His Gly Arg Asn Ala Ala Arg Lys Ala Ser Asp Leu Ile Ala Leu
acc gtc agg gaa tgc tgt tct cag cct ccc tgt cgc tgg aaa cat cca
Thr Val Arg Glu Cys Cys Ser Gln Pro Pro Cys Arg Trp Lys His Pro
gaa ctt tgt agt tga
Glu Leu Cys Ser
TABLE 93
DNA Sequence (SEQ ID NO:321) and Protein Sequence (SEQ ID NO:322) of G1.1
tct gat ggc agg aat gac gca gcc aaa gcg ttt gac ctg ata tct tcg
Ser Asp Gly Arg Asn Asp Ala Ala Lys Ala Phe Asp Leu Ile Ser Ser
acc gtc aag aaa gga tgc tgt tcc cat cct gcc tgt gcg ggg aat aat
Thr Val Lys Lys Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn Asn
caa cat att tgt ggc cga aga cgc tgatgctcca ggaccctctg aaccacgacg
Gln His Ile Cys Gly Arg Arg Arg
t
TABLE 94
DNA Sequence (SEQ ID NO:323) and Protein Sequence (SEQ ID NO:324) of G1.3
tct gat ggc agg aat gcc gca gcc aac gac caa gcg tct gac ctg atg
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Gln Ala Ser Asp Leu Met
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get gcg acc gtc agg gga tgc tgt gcc gtt cct tcc tgt cgc ctc cgt
Ala Ala Thr Val Arg Gly Cys Cys Ala Val Pro Ser Cys Arg Leu Arg
aat cca gac ctt tgt ggt gga gga cgc tgatgctcca ggaccctctg
Asn Pro Asp Leu Cys Gly Gly Gly Arg
aaccacgacg t
TABLE 95
DNA Sequence (SEQ ID NO:325) and Protein Sequence (SEQ ID NO:326) of Iml.3
ctt gat gaa agg aat gcc gca gcc gac gac aaa gcg tct gac ctg atc
Leu Asp Glu Arg Asn Ala Ala Ala Asp Asp Lys Ala Ser Asp Leu Ile
get caa atc gtc agg aga gga tgc tgt tcc cat cct gcc tgt aac gtg
Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Ala Cys Asn Val
aat aat cca cac att tgt ggt tga
Asn Asn Pro His Ile Cys Gly
TABLE 96
DNA Sequence (SEQ ID NO:327) and Protein Sequence (SEQ ID NO:328) of Lv1.2
tct gat ggc agg aat act gca gcc aaa gtc aaa tat tct aag acg ccg
Ser Asp Gly Arg Asn Thr Ala Ala Lys Val Lys Tyr Ser Lys Thr Pro
gag gaa tgc tgt ccc aat cct ccc tgt ttc gcg aca aat tcg gat att
Glu Glu Cys Cys Pro Asn Pro Pro Cys Phe Ala Thr Asn Ser Asp Ile
tgt ggc gga aga cgc tgatgctcca ggaccctctg aaccacgacg t
Cys Gly Gly Arg Arg
TABLE 97
DNA Sequence (SEQ ID NO:329) and Protein Sequence (SEQ ID NO:330) of Lvl.3
tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg
Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met
aag cgg acc gtc agg gat get tgc tgt tca gac cct cgc tgt tcc ggg
Lys Arg Thr Val Arg Asp Ala Cys Cys Ser Asp Pro Arg Cys Ser Gly
aaa cat caa gac ctg tgt ggc tgaagacgct gatgctccag gaccctctga
Lys His Gln Asp Leu Cys Gly
accacgacgt
TABLE 98
DNA Sequence (SEQ ID NO:331) and Protein Sequence (SEQ ID NO:332) of Lv1.4
tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg
Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met
gag ctg acc gtc agg gaa gat tgc tgt tca gac cct cgc tgt tcc gtg
Glu Leu Thr Val Arg Glu Asp Cys Cys Ser Asp Pro Arg Cys Ser Val
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gga cat caa gac ctg tgt ggc tgaagacgct gatgctccag gaccctctga
Gly His Gln Asp Leu Cys Gly
accacgacgt
TABLE 99
DNA Sequence (SEQ ID NO:333) and Protein Sequence (SEQ ID NO:334) of Lv1.6
gca ttt gat ggc agg aat get gca gcc agc gac aaa gcg tcc gag ctg
Ala Phe Asp Gly Arg Asn Ala Ala Ala Ser Asp Lys Ala Ser Glu Leu
atg get ctg gcc gtc agg gga tgc tgt tcc cat cct gcc tgt get ggg
Met Ala Leu Ala Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly
agt aat gca cat atc tgt ggc aga aga cgc tgatgctcca ggaccctctg
Ser Asn Ala His Ile Cys Gly Arg Arg Arg
aaccacgacg t
TABLE 100
DNA Sequence (SEQ ID NO:335) and Protein Sequence (SEQ ID NO:336) of Lvl.7
tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg
Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met
aag ctg acc gtc agg gag gat tgc tgt tca gac cct cgc tgt tcc gtg
Lys Leu Thr Val Arg Glu Asp Cys Cys Ser Asp Pro Arg Cys Ser Val
gga cat caa gac atg tgt ggc tgaagacgct gatgctccag gaccctctga
Gly His Gln Asp Met Cys Gly
atcacgacgt
TABLE 101
DNA Sequence (SEQ ID NO:337) and Protein Sequence (SEQ ID NO:338) of Lv1.8
ttt gaa tgc agg aat get gca ggc aac gac aaa gcg act gac ctg atg
Phe Glu Cys Arg Asn Ala Ala Gly Asn Asp Lys Ala Thr Asp Leu Met
get ctg act gtc agg gga tgc tgt tcc cat cct gcc tgt get ggg aat
Ala Leu Thr Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn
aat cca cat atc tgc ggc tgaagacgct gatgctccag gaccctctga
Asn Pro His Ile Cys Gly
accacgacgt
TABLE 102
DNA Sequence (SEQ ID NO:339) and Protein Sequence (SEQ ID NO:340) of Lv1.9
ttt gat ggc agg aac gcc gca gcc aac aac aaa gcg act gat ctg atg
Phe Asp Gly Arg Asn Ala Ala Ala Asn Asn Lys Ala Thr Asp Leu Met
get ctg act gtc aga gga tgc tgt ggc aat cct tca tgt agc atc cat
Ala Leu Thr Val Arg Gly Cys Cys Gly Asn Pro Ser Cys Ser Ile His
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att cct tac gtt tgt aat tagagacact gatgctccag gaccctctga
Ile Pro Tyr Val Cys Asn
accacgacgt
TABLE 103
DNA Sequence (SEQ ID NO:341) and Protein Sequence (SEQ ID NO:342) of Lv1.10
tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg
Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met
aag cgg acc gac agc gaa gaa tgc tgt tta gac tct cgc tgt gcc ggg
Lys Arg Thr Asp Ser Glu Glu Cys Cys Leu Asp Ser Arg Cys Ala Gly
caa cat caa gac ctg tgt ggc gga aga cgc tgatgctcca ggaccctctg
Gin His Gln Asp Leu Cys Gly Gly Arg Arg
aaccacgacg t
TABLE 104
DNA Sequence (SEQ ID NO:343) and Protein Sequence (SEQ ID NO:344) of Mr1.3
tct gat ggc agg aat gcc gca gcc aag gac aaa gcg tct gac ctg gtc
Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp Lys Ala Ser Asp Leu Val
get ctg acc gtc aag gga tgc tgt tct aat cct ccc tgt tac gcg aat
Ala Leu Thr Val Lys Gly Cys Cys Ser Asn Pro Pro Cys Tyr Ala Asn
aat caa gcc tat tgt aat gga aga cgc tga
Asn Gln Ala Tyr Cys Asn Gly Arg Arg
TABLE 105
DNA Sequence (SEQ ID NO:345) and Protein Sequence (SEQ ID NO:346) of Mrl.4
tct gat ggc agg aat gcc gca gcc aag gac aaa gcg tct gac ctg gtc
Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp Lys Ala Ser Asp Leu Val
get ctg acc gtc aag gga tgc tgt tct cat cct gcc tgt agc gtg aat
Ala Leu Thr Val Lys Gly Cys Cys Ser His Pro Ala Cys Ser Val Asn
aat cca gac att tgt ggt tga
Asn Pro Asp Ile Cys Gly
TABLE 106
DNA Sequence (SEQ ID NO:347) and Protein Sequence (SEQ ID NO:348) of Ms1.1
tct gat ggc agg aat get gca gcc aac aac aaa gtg get ttg acc atg
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asn Lys Val Ala Leu Thr Met
agg gga aaa tgc tgt atc aat gat gcg tgt cgc tcg aaa cat cca cag
Arg Gly Lys Cys Cys Ile Asn Asp Ala Cys Arg Ser Lys His Pro Gln
tac tgt tct gga aga cgc tgatactcca ggaccctctg aaccacgacg t
Tyr Cys Ser Gly Arg Arg
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TABLE 107
DNA Sequence (SEQ ID NO:349) and Protein Sequence (SEQ ID NO:350) of Ms1.6
tct gat ggc agg aat get gca gcc aac gac aaa gtg tct gac cag atg
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Val Ser Asp Gln Met
5 get ctg gtt gtc agg gga tgc tgt tac aat att gcc tgt aga att aat
Ala Leu Val Val Arg Gly Cys Cys Tyr Asn Ile Ala Cys Arg Ile Asn
aat cca cgg tac tgt cgt gga aaa cgc tgatgttcca ggaccctctg
Asn Pro Arg Tyr Cys Arg Gly Lys Arg
aaccacgacg t
10 TABLE 108
DNA Sequence (SEQ ID NO:351) and Protein Sequence (SEQ ID NO:352) of 01.1
tctgaaggca ggaatgccgc agccaacgac aaagcgtctg acctgatggc t ctg aac
Leu Asn
gtc agg gga tgc tgt tcc cat cct gtc tgt cgc ttc aat tat cca aaa
15 Val Arg Gly Cys Cys Ser His Pro Val Cys Arg Phe Asn Tyr Pro Lys
tat tgt ggt gga aga cgc tgatggtcca ggaccctctg aaccacgacg t
Tyr Cys Gly Gly Arg Arg
TABLE 109
DNA Sequence (SEQ ID NO:353) and Protein Sequence (SEQ ID NO:354) of 01.2
20 tctgatggcg ggaatgccgc agcaaaagcg tttgatctaa tcact ctg gcc ctc agg
Leu Ala Leu Arg
gat gaa tgc tgt gcc agt cct ccc tgt cgt ttg aat aat cca tac gta
Asp Glu Cys Cys Ala Ser Pro Pro Cys Arg Leu Asn Asn Pro Tyr Val
tgt cat tgacgacgct gatgctccag gaccctctga accacgacgt
25 Cys His
TABLE 110
DNA Sequence (SEQ ID NO:355) and Protein Sequence (SEQ ID NO:356) of 01.4
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
30 ccc act tca gat cgt gca tct gat agg agg aat gcc gca gcc aaa gcg
Pro Thr Ser Asp Arg Ala Ser Asp Arg Arg Asn Ala Ala Ala Lys Ala
ttt gac ctg aga tat tcg acc gcc aag aga gga tgc tgt tcc aat cct
Phe Asp Leu Arg Tyr Ser Thr Ala Lys Arg Gly Cys Cys Ser Asn Pro
gtc tgt tgg cag aat aat gca gaa tac tgt cgt gaa agt ggc
35 Val Cys Trp Gln Asn Asn Ala Glu Tyr Cys Arg Glu Ser Gly
taatgctcca ggaccctctg aaccacgacg t
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TABLE 111
DNA Sequence (SEQ ID NO:357) and Protein Sequence (SEQ ID NO:358) of 01.7
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
ttc act tca gat cgt gca tct gat ggc ggg aat gtc gca gcg tct cac
Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Val Ala Ala Ser His
ctg atc get ctg acc atc aag gga tgc tgt tct cac cct ccc tgt gcc
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Ala
cag aat aat caa gac tat tgt ggt tgacgacgct gatgctccag gaccctctga
Gln Asn Asn Gln Asp Tyr Cys Gly
accacgacgt
TABLE 112
DNA Sequence (SEQ ID NO:359) and Protein Sequence (SEQ ID NO:360) of 01.8
atg ttc acc gtg ttt ctg ttg gtt gtc tta tca acc acc gtc gtt tcc
Met Phe Thr Val Phe Leu Leu Val Val Leu Ser Thr Thr Val Val Ser
tcc act tca gat cgt gca tct gat agg agg aat gcc gca gcc aaa gcg
Ser Thr Ser Asp Arg Ala Ser Asp Arg Arg Asn Ala Ala Ala Lys Ala
tct gac ctg atg tat tcg acc gtc aag aaa gga tgt tgt tcc cat cct
Ser Asp Leu Met Tyr Ser Thr Val Lys Lys Gly Cys Cys Ser His Pro
gcc tgt tcg ggg aat aat cga gaa tat tgt cgt gaa agt ggc
Ala Cys Ser Gly Asn Asn Arg Glu Tyr Cys Arg Glu Ser Gly
taatgctcca ggaccctctg aaccacgacg t
TABLE 113
DNA Sequence (SEQ ID NO:361) and Protein Sequence (SEQ ID NO:362) of Om1.2
tttgatggca ggaatgcctc agccgacagc aaagtggctg cccggatcgc t cag atc
Gln Ile
gac agg gat cca tgc tgt tcc tat cct gac tgt ggc gcg aat cat cca
Asp Arg Asp Pro Cys Cys Ser Tyr Pro Asp Cys Gly Ala Asn His Pro
gag att tgt ggt gga aaa cgc tgatgctcca ggaccctctg aaccacgacg t
Glu Ile Cys Gly Gly Lys Arg
TABLE 114
DNA Sequence (SEQ ID NO:363) and Protein Sequence (SEQ ID NO:364) of Om1.3
tctcatggca ggaatgccgc acgct ctg acc gtc agg gaa tgc tgt tct cag
Leu Thr Val Arg Glu Cys Cys Ser Gln
cct cct tgt cgc tgg aaa cat cca gaa ctt tgt agt tgaagacgct
Pro Pro Cys Arg Trp Lys His Pro Glu Leu Cys Ser
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gatgctccag gaccctctga accacgacgt
TABLE 115
DNA Sequence (SEQ ID NO:365) and Protein Sequence (SEQ ID NO:366) of Oml.4
tttgatggca ggaatgctgc agccagcgac aaagcgtctg agctgatggc t ctg gcc
Leu Ala
gtc agg gga tgc tgt tcc cat cct gcc tgt get ggg aat aat cca cat
Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn Asn Pro His
atc tgt ggc aga aga cgc tgatgctcca ggaccctctg aaccacgacg t
Ile Cys Gly Arg Arg Arg
TABLE 116
DNA Sequence (SEQ ID NO:367) and Protein Sequence (SEQ ID NO:368) of Oml.5
tctggtgtca ggaaagacgc agcgcctggc ctgatcgct ctg acc atc aag gga
Leu Thr Ile Lys Gly
tgc tgt tct gat cct agc tgt aac gtg aat aat cca gac tat tgt ggt
Cys Cys Ser Asp Pro Ser Cys Asn Val Asn Asn Pro Asp Tyr Cys Gly
tgacgacgct gatgctccag gaccctctga accacgacgt
TABLE 117
DNA Sequence (SEQ ID NO:369) and Protein Sequence (SEQ ID NO:370) of Om1.6
tctaatggca ggaatgccgc agccaaattc aaagcgcctg ccctgatgga g ctg acc 57
Leu Thr
gtc agg gaa gaa tgc tgt tca gac cct cgc tgt tcc gtg gga cat caa 105
Val Arg Glu Glu Cys Cys Ser Asp Pro Arg Cys Ser Val Gly His Gln
gat atg tgt cgg tgaagcacgt gatgctccag gaccctctga accacgacgt 157
Asp Met Cys Arg
TABLE 118
DNA Sequence (SEQ ID NO:371) and Protein Sequence (SEQ ID NO:372) of P1.4
act gat ggc agg aat get gca gcc ata gcg ctt gac ctg atc get ccg
Thr Asp Gly Arg Asn Ala Ala Ala Ile Ala Leu Asp Leu Ile Ala Pro
gcc gtc agg gga gga tgc tgt tcc aat cct gcc tgt tta gtg aat cat
Ala Val Arg Gly Gly Cys Cys Ser Asn Pro Ala Cys Leu Val Asn His
cta gaa atg tgt ggt aaa aga cgc tgatgcccca ggaccctctg aaccacgacg
Leu Glu Met Cys Gly Lys Arg Arg
t
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TABLE 119
DNA Sequence (SEQ ID NO:373) and Protein Sequence (SEQ ID NO:374) of P1.5
tct gat ggc agg gat gcc gca gcc aac gac aaa gcg tct gac ctg atc
Ser Asp Gly Arg Asp Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Ile
get ctg acc gcc agg aga gat cca tgc tgt ttc aat cct gcc tgt aac
Ala Leu Thr Ala Arg Arg Asp Pro Cys Cys Phe Asn Pro Ala Cys Asn
gtg aat aat cca cag att tgt ggt tgaagacgct gatgctccag gaccctctga
Val Asn Asn Pro Gln Ile Cys Gly
accacgacgt
TABLE 120
DNA Sequence (SEQ ID NO:375) and Protein Sequence (SEQ ID NO:376) of P1.6
tct gat ggc agg gat get gag aaa aca ggc ttt gac acg acc att gtg
Ser Asp Gly Arg Asp Ala Glu Lys Thr Gly Phe Asp Thr Thr Ile Val
ccg gaa gac tgc tgt tcg gat cct tcc tgt tgg agg ctg cat agt tta
Pro Glu Asp Cys Cys Ser Asp Pro Ser Cys Trp Arg Leu His Ser Leu
get tgt act gga att gta aac cgc tgatgctcca ggaccctctg aaccacgacg
Ala Cys Thr Gly Ile Val Asn Arg
t
TABLE 121
DNA Sequence (SEQ ID NO:377) and Protein Sequence (SEQ ID NO:378) of P1.8
act gat ggc agg agt get gca gcc ata gcg ttt gcc ctg atc get ccg
Thr Asp Gly Arg Ser Ala Ala Ala Ile Ala Phe Ala Leu Ile Ala Pro
acc gtc tgc tgt act aat cct gcc tgt ctc gtg aat aat ata cgc ttt
Thr Val Cys Cys Thr Asn Pro Ala Cys Leu Val Asn Asn Ile Arg Phe
tgt ggt gga aga cgc tgatgcccca ggaccctctg aaccacgacg t
Cys Gly Gly Arg Arg
TABLE 122
DNA Sequence (SEQ ID NO:379) and Protein Sequence (SEQ ID NO:380) of Rgl.1
tct gat gga aga aat gcc gca agc gac gcc aaa gcg ttt ccc cgg atc
Ser Asp Gly Arg Asn Ala Ala Ser Asp Ala Lys Ala Phe Pro Arg Ile
get cca atc gtc agg gac gaa tgc tgt agc gat cct agg tgt cac ggg
Ala Pro Ile Val Arg Asp Glu Cys Cys Ser Asp Pro Arg Cys His Gly
aat aat cgg gac cac tgt get tgaagacgct gctgctccag gaccctctga
Asn Asn Arg Asp His Cys Ala
accacgacgt
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TABLE 123
DNA Sequence (SEQ ID NO:381) and Protein Sequence (SEQ ID NO:382) of Rg1.3
tct gat ggc agg aat acc gcg gcc gac gaa aaa gcg tcc gac ctg atc
Ser Asp Gly Arg Asn Thr Ala Ala Asp Glu Lys Ala Ser Asp Leu Ile
tct caa act gtc aag aga gat tgc tgt tcc cat cct ctc tgt aga tta
Ser Gln Thr Val Lys Arg Asp Cys Cys Ser His Pro Leu Cys Arg Leu
ttt gtt cca gga ctt tgt att tgaagacgct gctgctccag gaccctctga
Phe Val Pro Gly Leu Cys Ile
accacgact
TABLE 124
DNA Sequence (SEQ ID NO:383) and Protein Sequence (SEQ ID NO:384) of Rg1.4
tct gat ggc agg aat gcc gca gcc gac aac aaa gcg tct gac cta atc
Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Lys Ala Ser Asp Leu Ile
get caa atc gtc agg aga gga tgc tgt tcc cat cct gtc tgt aaa gtg
Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Val Cys Lys Val
agg tat cca gac ctg tgt cgt tgaagacgct gctgctccag gaccctctga
Arg Tyr Pro Asp Leu Cys Arg
accacgacgt
TABLE 125
DNA Sequence (SEQ ID NO:385) and Protein Sequence (SEQ ID NO:386) of Rg1.5
tct gat ggc agg aat gcc gca gcc gac aac aga gcg tct gac cta atc
Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Arg Ala Ser Asp Leu Ile
get caa atc gtc agg aga gga tgc tgt tcc cat cct gcc tgt aat gtg
Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Ala Cys Asn Val
aat aat cca cac att tgt ggt tgaagacgct gctgctccag gaccctctga
Asn Asn Pro His Ile Cys Gly
accacgacgt
TABLE 126
DNA Sequence (SEQ ID NO:387) and Protein Sequence (SEQ ID NO:-3 )88) of Rg1.8
tct gat ggc agg aat gcc gca gcc gac aac aaa ccg tct gac cta atc
Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Lys Pro Ser Asp Leu Ile
get caa atc gtc agg aga gga tgc tgt tcg cat cct gtc tgt aaa gtg
Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Val Cys Lys Val
agg tat tca gac atg tgt ggt tgaagacgct gctgctccag gaccctctga
Arg Tyr Ser Asp Met Cys Gly
accacgacgt
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TABLE 127
DNA Sequence (SEQ ID NO:389) and Protein Sequence (SEQ ID NO:390) of Sml.4
tct gat ggc agg aat gca gag cga cga caa agc gtc tgt cct ggt cgc
Ser Asp Gly Arg Asn Ala Glu Arg Arg Gin Ser Val Cys Pro Gly Arg
5 tct ggc ccc agg gga gga tgt tgt tcc cac cct gcc tgt aag gtg cat
Ser Gly Pro Arg Gly Gly Cys Cys Ser His Pro Ala Cys Lys Val His
ttt cca cac agt tgt ggt tgacgacgct gatgctccag gaccctctga
Phe Pro His Ser Cys Giy
accacgacgt
10 TABLE 128
DNA Sequence (SEQ ID NO:391) and Protein Sequence (SEQ ID NO:392) of Sml.5
tct gat ggc agg aat gcc gca gcc agc gac aga gcg tct gac gcg gcc
Ser Asp Gly Arg Asn Ala Ala Ala Ser Asp Arg Ala Ser Asp Ala Ala
cac cag gta tgc tgt tcc aac cct gtc tgt cac gtg gat cat cca gaa
15 His Gln Val Cys Cys Ser Asn Pro Val Cys His Val Asp His Pro Glu
ctt tgt cgt aga aga cgc tgatgctcca ggaccctctg aaccacgacg t
Leu Cys Arg Arg Arg Arg
TABLE 129
DNA Sequence (SEQ ID NO:393) and Protein Sequence (SEQ ID NO:394) of S1.5
20 tct gat ggc agg aat gcc gcg gcc aac gac aaa gcg tct gac ctg gtc
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Val
get ccg gcc atc agg gga tgc tgt tcc cac cct gtc tgt aac ttg agt
Ala Pro Ala Ile Arg Gly Cys Cys Ser His Pro Val Cys Asn Leu Her
aat cca caa att tgt cgt gga aga cgc tgatgctcca ggaccctctg
25 Asn Pro Gin Ile Cys Arg Gly Arg Arg
aaccacgacg t
TABLE 130
DNA Sequence (SEQ ID NO:395) and Protein Sequence (SEQ ID NO:396) of Tx1.5
ttt cat ggc agg aat gcc gca gcc aaa gcg tct ggc ctg gtc ggt ctg
30 Phe His Gly Arg Asn Ala Ala Ala Lys Ala Ser Gly Leu Val Gly Leu
acc gac aag agg caa gaa tgc tgt tct cat cct gcc tgt aac gta gat
Thr Asp Lys Arg Gln Glu Cys Cys Ser His Pro Ala Cys Asn Val Asp
cat cca gaa att tgt cgt tga
His Pro Glu Ile Cys Arg
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TABLE 131
DNA Sequence (SEQ ID NO:397) and Protein Sequence (SEQ ID NO:398) of T1.1
act gat ggc agg agt get gca gcc ata gcg ttt gcc ctg atc get ccg
Thr Asp Gly Arg Ser Ala Ala Ala Ile Ala Phe Ala Leu Ile Ala Pro
acc gtc tgg gaa gga tgc tgt tct aat cct gcc tgt ctc gtg aat cat
Thr Val Trp Glu Gly Cys Cys Ser Asn Pro Ala Cys Leu Val Asn His
ata cgc ttt tgt ggt gga aga cgc tgatgcccca ggaccctctg aaccacgacg
Ile Arg Phe Cys Gly Gly Arg Arg
t
TABLE 132
DNA Sequence (SEQ ID NO:399) and Protein Sequence (SEQ ID NO:400) of Vr1.3
tct aat ggc atg aat gcc gca gcc atc agg aaa gcg tct gcc ctg gtg
Ser Asn Gly Met Asn Ala Ala Ala Ile Arg Lys Ala Ser Ala Leu Val
get cag atc gcc cat cga gac tgc tgt gac gat cct gcc tgc acc gtg
Ala Gln Ile Ala His Arg Asp Cys Cys Asp Asp Pro Ala Cys Thr Val
aat aat cca ggc ctt tgc act tgaagatgct gctgccccag gaccctctga
Asn Asn Pro Gly Leu Cys Thr
accacgacgt
TABLE 133
DNA Sequence (SEQ ID NO:401) and Protein Sequence (SEQ ID NO:402) of G1.2
tct gat ggc ggg aat gcc gca gca aaa gag tct gac gtg atc get ctg
Ser Asp Gly Gly Asn Ala Ala Ala Lys Glu Ser Asp Val Ile Ala Leu
acc gtc tgg aaa tgc tgt acc att cct tcc tgt tat gag aaa aaa aaa
Thr Val Trp Lys Cys Cys Thr Ile Pro Ser Cys Tyr Glu Lys Lys Lys
att aaa gca tgt gtc ttt tgacgacgct gatgctccag gaccctctga
Ile Lys Ala Cys Val Phe
accacgacgt
TABLE 134
DNA Sequence (SEQ ID NO:403) and Protein Sequence (SEQ ID NO:404) of Rgl .12
tct gat ggc gca gtc gac gac aaa gcg ttg gat cga atc get gaa atc
Ser Asp Gly Ala Val Asp Asp Lys Ala Leu Asp Arg Ile Ala Glu Ile
gtc agg aga gga tgc tgt ggc aat cct gcc tgt agc ggc tcc tcg aaa
Val Arg Arg Gly Cys Cys Gly Asn Pro Ala Cys Ser Gly Ser Ser Lys
gat gca ccc tct tgt ggt tgaagacgct gctgctccag gaccctctga
Asp Ala Pro Ser Cys Gly
accacgacgt
CA 02361534 2001-07-26
WO 00/44776 PCTIUSOO/01979
67
It will be appreciated that the methods and compositions of the instant
invention can be
incorporated in the form of a variety of embodiments, only a few of which are
disclosed herein. It
will be apparent to the artisan that other embodiments exist and do not depart
from the spirit of the
invention. Thus, the described embodiments are illustrative and should not be
construed as
restrictive.
LIST OF REFERENCES
Barnay, G. et al. (2000). J. Med. Chem.
Bitan, G. et al. (1997). J. Peptide Res. 49:421-426.
Blount, K. et al. (1992). Toxicon 30:835-842.
Bodansky et al. (1966). Chem. Ind. 38:1597-98.
Cartier, G.E. et al. (1996). J. Biol. Chem. 271:7522-7528.
Cruz, L.J. at al. (1976). Verliger 18:302-308.
Cruz, L.J. et al. (1987). J Biol. Chem. 260:9280-9288.
Fainzilber, M. et al. (1994). Biochemistry 33:9523-9529.
Gray, W.R. et al. (1981). J.Biol. Chem. 256:4734-4740.
Haack, J.A. et al. (1990). J. Biol. Chem. 265:6025-6029.
Horiki, K. et al. (1978). Chemistry Letters 165-68.
Hubry, V. et al. (1994). Reactive Polymers 22:231-241.
Jacobsen, R. et al. (1997). 1 Biol. Chem. 272:22531-22537.
Johnson, D.S. et al. (1995). Mol. Pharmacol. 48:194-199.
Kapoor (1970). J. Pharm. Sci. 59:1-27.
Kornreich, W.D. et al. (1986). U.S. Patent No. 4,569,967.
Luo, S. et al. (1998). J. Neurosci. 18:8571-8679.
Marshall, I.G. and Harvey, A.L. (1990). Toxicon 28:231-234.
Martinez, J.S. et al. (1995). Biochem. 34:14519-14526.
McIntosh, J.M. et al. (1982). Arch. Biochem. Biophys. 218:329-334.
Mena, E.E. et al. (1990). Neurosci. Lett. 118:241-244.
Methoden der Organischen Chemie (Houben-Weyl): Synthese von Peptiden, E.
Wunsch (Ed.),
Georg Thieme Verlag, Stuttgart, Ger. (1974).
Myers, R.A. et al. (1991). Biochemistry 30:9370-9377.
Nishiuchi, Y. et al. (1993). Int. J. Pept. Protein Res. 42:533-538.
CA 02361534 2001-07-26
WO 00/44776 PCT/US00/01979
68
Nowak, L. et al. (1984). Nature 307:462-465.
Olivera, B.M. et al. (1984). U.S. Patent 4,447,356.
Olivera, B.M. et al. (1985). Science 230:1338-1343.
Olivera, B.M. et al. (1996). U.S. Patent 5,514,774.
Rivier, J.R. et al. (1978). Biopolymers 17:1927-38.
Rivier, J.R. et al. (1987). Biochem. 26:8508-8512.
Sambrook, J. et al. (1989). Molecular Cloning: A Laboratory Manual, 2nd Ed.,
Cold Spring Harbor
Laboratory, Cold Spring Harbor, NY.
Schroder & Lubke (1965). The Peptides 1:72-75, Academic Press, NY.
Shon, K.-J. et al. (1994). Biochemistry 33:11420-11425.
Stewart and Young, Solid-Phase Peptide Synthesis, Freeman & Co., San
Francisco, CA (1969).
Vale et al. (1978). U.S. Patent 4,105,603.
Van de Steen, P. et al. (1998). Critical Rev. in Biochem. and Mol. Biol.
33:151-208.
Zafaralla, G.C. et al. (1988). Biochemistry 27:7102-7105.
Zhou L.M., et al. (1996). J Neurochem. 66:620-628.
U.S. Patent No. 3,972,859.
U.S. Patent No. 3,842,067.
U.S. Patent No. 3,862,925.
U.S. Patent No. 5,550,050.
PCT Published Application WO 92/19195.
PCT Published Application WO 94/25503.
PCT Published Application WO 95/01203.
PCT Published Application WO 95/05452.
PCT Published Application WO 96/02286.
PCT Published Application WO 96/02646.
PCT Published Application WO 96/11698.
PCT Published Application WO 96/40871.
PCT Published Application WO 96/40959.
PCT Published Application WO 97/12635.
CA 02361534 2002-02-22
1.
SEQUENCE LISTING
<110> Cognetix, Inc.
University Of Utah Research Foundation
<120> Alpha-Conotoxin Peptides
<130> 08-892290CA
<140> 2,361,534
<141> 2000-01-28
<150> US 60/118,381
<151> 1999-01-29
<160> 404
<170> Patentln Ver. 2.0
<210> 1
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Alpha-Conotoxin
Peptide Generic Formula I
<220>
<221> PEPTIDE
<222> (1) .. (3)
<223> Xaa at residue 1 is des-Xaa, Ile, Leu or Val; Xaa
at residue 2 is des-Xaa, Ala or Gly; Xaa at
residue 3 is des-Xaa, Gly, Trp (D or L), neo-Trp,
halo-Trp or any unnatural aromatic amino acid.
<220>
<221> PEPTIDE
<222> (4)
<223> N-methyl-Lys, Xaa at residue 4 is des-Xaa, Gly,
Trp (D or L), neo--Trp, halo-Trp or any unnatural
aromatic amino acid.
<220>
<221> PEPTIDE
<222> (5)
<223> Xaa at residue 5 is Glu, gamma-carboxy-Glu (Gla), Asp,
Ala, Thr, Ser, Gly, Ile, Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, 0-phospho-Tyr, nitro-Tyr or
any unnatural hydroxy containing amino acid.
<220>
<221> PEPTIDE
<222> (8)
<223> Xaa at residue 8 is Ser, Thr, Arg, ornithine,
homoarginine, Lys,, N,N-dimethyl-Lys, N,N,N-trimethyl-
CA 02361534 2002-02-22
Lys or any unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (9)
<223> Xaa at residue 9 is Asp, Glu, Gla, Arg, ornithine,
homoarginine, Lys, N-methyl-Lys,N,N-dimethyl-Lys,
N,N,N-trimethyl-Lys or any unnatural basic amino
acid.
<220>
<221> PEPTIDE
<222> (10)
<223> Xaa at residue 10 is Ser, Thr, Asn, Ala, Gly,
His, halo-His, Pro or hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (11)
<223> Xaa at residue 11 is Thr, Ser, Ala, Asp, Asn,
Pro, hydroxy-Pro, Arg, ornithine, homoarginine,
Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-
trimethyl-Lys or any unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (13)
<223> Xaa at residue 13 is Gly, Ser, Thr, Ala, Asn,
Arg, ornithine, homoarginine, Lys, N-methyl-Lys,
N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any
unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (14)
<223> Xaa at residue 14 is Gln, Leu, His, halo-His,
Trp (D or L), halo-Trp, neo-Trp, Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, 0-sulpho-Tyr,
0-phospho-Tyr, nitro-Tyr, Arg, ornithine.
<220>
<221> PEPTIDE
<222> (14)
<223> Xaa at residue 14 is also homoarginine, Lys,
N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-
Lys, any unnatural basic amino acid or any
unnatural aromatic amino acid-
<220>
<221> PEPTIDE
<222> (15)
<223> Xaa at residue 15 is Asn, His, halo-His, Ile, Leu,
Val, Gln, Arg, ornithine, homoarginine, Lys,
N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-
CA 02361534 2002-02-22
3
Lys or any unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (17)
<223> Xaa at residue 17 is des-Xaa, Val, Ile, Leu, Arg,
ornithine, homoarginine, Lys, N-methyl-Lys, N,N-
dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural
basic amino acid.
<400> 1
Xaa Xaa Xaa Xaa Xaa Cys Cys Xaa Xaa Xaa Xaa Cys Xaa Xaa Xaa Cys
1 5 10 15
Xaa
<210> 2
<211> 21
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence:Alpha-Conotoxin
Peptide Generic Formula II.
<220>
<221> PEPTIDE
<222> (1)..(3)
<223> Xaa at residue 1 is des-Xaa, Asp, Glu or gamma-
carboxy-Glu (Gla); Xaa at residue 2 is des-Xaa,
Gln, Ala, Asp, Glu, Gla; Xaa at residue 3 is des-
Xaa, Gly, Ala, Asp, Glu, Gla, Pro or hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (4)
<223> Xaa at residue 4 is des-Xaa, Gly, Glu, Gla, Gln,
Asp, Asn, Pro or hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (7)
<223> Xaa at residue 7 is Ser, Thr, Gly, Glu, Gla, Asn,
Trp (D or L), neo-Trp, halo-Trp, Arg, ornithine,
homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys,
N,N,N-trimethyl-Lys, any unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (7)
<223> Xaa at residue 7 is also Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, 0-phospho-Tyr, nitro-Tyr
or any unnatural hydroxy containing amino acid.
CA 02361534 2002-02-22
<220>
<221> PEPTIDE
<222> (8)
<223> Xaa at residue 8 is Asp, Asn, His, halo-His, Thr,
Ser, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, 0-phospho-Tyr, nitro-Tyr or any
unnatural hydroxy containing amino acid.
<220>
<221> PEPTIDE
<222> (9)
<223> Xaa at residue 9 is Pro or hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (10)
<223> Xaa at residue 10 is Ala, Ser, Thr, Asp, Val, Ile,
Pro, hydroxy-Pro, Tyr, nor-Tyr, mono-halo-Tyr, di-
halo-Tyr, 0-sulpha-Tyr, 0-phospho-Tyr, nitro-Tyr or
any unnatural hydroxy containing amino acid.
<220>
<221> PEPTIDE
<222> (12)
<223> Xaa at residue 12 is Gly, Ile, Leu, Val, Ala, Thr,
Ser, Pro, hydroxy-Pro, Phe, Trp (D or L), neo-Trp,
halo-Trp, Arg, ornithine, homoarginine, Lys, N-
methyl-Lys, N,N-dimethyl-Lys.
<220>
<221> PEPTIDE
<222> (12)..(13)
<223> Xaa at residue 12 is also N,N,N-trimethyl-Lys, any
unnatural basic amino acid or any unnatural aromatic
amino acid; Xaa at residue 13 is Ala, Asn, Phe, Pro,
hydroxy-Pro, Glu, Gla, Gln, His, halo-His, Val, Ser.
<220>
<221> PEPTIDE
<222> (13)
<223> Xaa at residue 13 is also Thr, Arg, ornithine,
homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys,
N,N,N-trimethyl-Lys or any unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (14)
<223> Xaa at residue 14 is Thr, Ser, His, halo-His, Leu,
Ile, Val, Asn, Met:, Pro, hydroxy-Pro, Arg, ornithine,
homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys,
N,N,N-trimethyl-Lys, any unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (14) .. (15)
CA 02361534 2002-02-22
<223> Xaa at residue 14 is also Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or
any unnatural hydroxy containing amino acid; Xaa at
residue 15 is Asn, Pro, hydroxy-Pro, Gln, Ser, Thr.
<220>
<221> PEPTIDE
<222> (15)
<223> Xaa at residue 15 is also Thr, Arg, ornithine,
homoarginine, Lys, N-=methyl-Lys, N,N-dimethyl-Lys,
N,N,N-trimethyl-Lys, any unnatural basic amino acid,
Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr.
<220>
<221> PEPTIDE
<222> (15)..(16)
<223> Xaa at residue 15 is also 0-phospho-Tyr, nitro-Tyr
or any unnatural hydroxy containing amino acid; Xaa
at residue 16 is des-Xaa, Gly, Thr, Ser, Pro, hydroxy-
Pro, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr.
<220>
<221> PEPTIDE
<222> (16)
<223> Xaa at residue 16 is also O-sulpho-Tyr, 0-phospho-Tyr,
nitro-Tyr or any unnatural hydroxy containing amino
acid.
<220>
<221> PEPTIDE
<222> (17)
<223> Xaa at residue 17 is des-Xaa, Ile, Val, Asp, Leu, Phe,
Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-
dimethyl-Lys, N,N,N-trimethyl-Lys, any unnatural basic
amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr.
<220>
<221> PEPTIDE
<222> (17) .. (19)
<223> Xaa at residue 17 is also O-sulpho-Tyr, 0-phospho-Tyr,
nitro-Tyr or any unnatural hydroxy containing amino
acid; Xaa at residue 19 is des-Xaa, Gly, Ala, Met, Ser,
Thr, Trp (D or L), neo-Trp, halo-Trp.
<220>
<221> PEPTIDE
<222> (19)
<223> Xaa at residue 19 is also any unnatural aromatic
amino acid, Arg, ornithine, homoarginine, Lys, N-
methyl-Lys, N,N-d:i.methyl-Lys, N,N,N-trimethyl-Lys or
any unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (20)
CA 02361534 2002-02-22
6
<223> Xaa at residue 20 is des-Xaa, Trp (D or L), neo-Trp,
halo-Trp, any unnatural aromatic amino acid, Arg,
ornithine, homoargirine, Lys, N-methyl-Lys.
<220>
<221> PEPTIDE
<222> (20)
<223> Xaa at residue 20 is also N,N-di-methyl-Lys, N,N,N-
trimethyl-Lys or any unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (21)
<223> Xaa at residue 21 is des-Xaa, Arg, ornithine,
homoarginine, Lys, N--methyl--Lys, N,N-dimethyl-Lys,
N,N,N-trimethyl-Lys or any unnatural basic amino
acid.
<400> 2
Xaa Xaa Xaa Xaa Cys Cys Xaa Xaa Xaa Xaa Cys Xaa Xaa Xaa Xaa Xaa
1 5 10 15
Xaa Cys Xaa Xaa Xaa
<210> 3
<211> 28
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence.Alpha-Conotoxin
Peptide Generic Formula III.
<220>
<221> PEPTIDE
<222> (1)..(3)
<223> Xaa at residue 1 is des-Xaa, Ser or Thr; Xaa at
residue 2 is des-Xaa, Asp, Glu, gamma-carboxy-Glu
(Gla), Asn, Ser or Thr; Xaa at residue 3 is des-
Xaa, Ala, Gly, Asn, Ser, Thr, Pro, hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (3)
<223> Xaa at residue 3 is also Arg, ornithine, homoarginine,
Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-
Lys or any unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (4) ... (5)
<223> Xaa at residue 4 is des-Xaa, Ala, Val, Leu, Ile, Gly,
Glu, Gla, Gln, Asp, Asn, Phe, Pro, hydroxy-Pro or any
CA 02361534 2002-02-22
unnatural aromatic amino acid Xaa at residue 5 is
des-Xaa, Thr, Ser, Asp, Glu, Gla, Gin, Gly, Val, Asp.
<220>
<221> PEPTIDE
<222> (5)
<223> Xaa at residue 5 is also Asn, Ala, Pro, hydroxy-Pro,
Arg, ornithine, homo-arginine, Lys, N-methyl-Lys,
N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any
unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (8)
<223> Xaa at residue 8 is Thr, Ser, Asp, Asn, Met, Val, Ala,
Gly, Leu, Ile, Phe, any unnatural aromatic amino acid,
Pro, hydroxy-Pro, Tyr, nor-Tyr, mono-halo-Tyr, di-
halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr.
<220>
<221> PEPTIDE
<222> (8) .. (9)
<223> Xaa at residue 8 is also nitro-Tyr or any unnatural
hydroxy containing amino acid; Xaa at residue 9 is
Ile, Leu, Val, Ser, Thr, Gln, Asn, Asp, Arg, His,
halo-His, Phe.
<220>
<221> PEPTIDE
<222> (9)
<223> Xaa at residue 9 is also any unnatural aromatic amino
acid, homoarginine, ornithine, Lys, N-methyl-Lys,
N,N-dimethyl-Lys, N,N,N--trimethyl-Lys, any unnatural
basic amino acid, Tyr, nor-Tyr, mono-halo-Tyr.
<220>
<221> PEPTIDE
<222> (9) .. (10)
<223> Xaa at residue 9 is also di-halo-Tyr, 0-sulpho-Tyr,
0-phospho-Tyr, nitro-Tyr or any unnatural hydroxy
containing amino acid; Xaa at residue 10 is Pro,
hyroxy-Pro, Ser, Thr, Ile, Asp, Leu, Val, Gly, Ala.
<220>
<221> PEPTIDE
<222> (10)
<223> Xaa at residue 10 is also Phe, any unnatural
aromatic amino acid, Arg, ornithine, homoarginine,
Lys, N-methyl-Lys, N,N-dimethyl-.Lys, N,N,N-tri-
methyl-Lys or any unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (11)
<223> Xaa at residue 11 is Val, Ala, Gly, Ile, Leu, Asp,
Ser, Thr, Pro, hydroxy-Pro, Arg,. ornithine,
CA 02361534 2002-02-22
8
homoarginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys.
<220>
<221> PEPTIDE
<222> (11)..(13)
<223> Xaa at residue 11 is also N,N,N-trimethyl-Lys or any
unnatural basic amino acid; Xaa at residue 13 is His,
halo-His, Arg, homoarginine, ornithine, Lys, N-methyl-
Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys.
<220>
<221> PEPTIDE
<222> (13)
<223> Xaa at residue 13 is also any unnatural basic amino
acid, Asn, Ala,Ser, Thr, Phe, Ile, Leu, Gly, Trp
(D or L), neo-Trp, halo-Trp, any unnatural aromatic
amino acid, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr.
<220>
<221> PEPTIDE
<222> (13)..(14)
<223> Xaa at residue 13 is also 0-sulpho-Tyr, 0-phospho-Tyr,
nitro-Tyr or any unnatural hydroxy containing amino
acid; Xaa at residue 14 is Leu, Gln, Val, Ile, Gly,
Met, Ala, Lys, N-methyl-Lys, N,N-dimethyl-Lys.
<220>
<221> PEPTIDE
<222> (14)
<223> Xaa at residue 14 is also N,N,N-tri-methyl-Lys,
Ser, Thr, Arg, homoarginine, ornithine, any unnatural
basic amino acid, Asn, Glu, Gla, Gln, Phe, Trp (D or L).
<220>
<221> PEPTIDE
<222> (14)..(15)
<223> Xaa at residue 14 is also neo-Trp, halo-Trp or any
unnatural aromatic amino acid; Xaa at residue 15
is Glu, Gla, Gln, Asn, Asp, Pro, hydroxy-Pro, Ser,
Gly, Thr, Lys, N-methyl-Lys, N,N-dimethyl-Lys.
<220>
<221> PEPTIDE
<222> (15)
<223> Xaa at residue 15 is also N,N,N-trimethyl-Lys, Arg,
homoarginine, ornithine, any unnatural basic amino
acid, Phe, His, halo-His, any unnatural aromatic acid,
Leu, Met, Gly, Ala, Tyr, nor-Tyr, mono-halo-Tyr.
<220>
<221> PEPTIDE
<222> (15)..(16)
<223> Xaa at residue 15 is also di-halo-Tyr, 0-sulpho-Tyr,
0-phospho-Tyr, nitro-Tyr or any unnatural hydroxy
containing amino acid; Xaa at residue 16 is His,
CA 02361534 2002-02-22
'l
halo-His, Asn, Thr, Ser, Ile, Val, Leu, Phe.
<220>
<221> PEPTIDE
<222> (16)
<223> Xaa at residue 16 is also any unnatural aromatic
amino acid, Arg, homoarginine, ornithine, Lys, N-
methyl-Lys, N,N-di.methyl-Lys, N,N,N-trimethyl-Lys,
any unnatural basic amino acid, Tyr, nor-Try.
<220>
<221> PEPTIDE
<222> (16)..(17)
<223> Xaa at residue 16 is also mono-halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, 0-phospho-Tyr, nitro-Tyr or any
unnatural hydroxy containing amino acid; Xaa at
residue 17 is Ser, Thr, Ala, Gln, Pro, hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (17)
<223> Xaa at residue 17 is also Gly, Ile, Leu, Arg,
ornithine, homoarginine, Lys, N-methyl-Lys,
N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any
unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (18)
<223> Xaa at residue 18 is Asn, Glu, Gla, Asp, Gly, His,
halo-His, Ala, Leu, Gln, Arg, ornithine, homo-
arginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys,
N,N,N-trimethyl-Lys, any unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (18)
<223> Xaa at residue 18 is also Tyr, nor-Tyr, mono-halo-
Tyr, di-halo-Tyr, O-sulpho-Tyr, 0-phospho-Tyr,
nitro-Tyr or any unnatural hydroxy containing amino
acid.
<220>
<221> PEPTIDE
<222> (19)
<223> Xaa at residue 19 is Met, Ile, Thr, Ser, Val, Leu,
Pro, hydroxy-Pro, Phe, any unnatural aromatic amino
acid, Tyr, nor-Tyr, mono- halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, 0-phospho-Tyr, nitro-Tyr.
<220>
<221> PEPTIDE
<222> (19)
<223> Xaa at residue 19 is also any unnatural hydroxy
containing amino acid, Glu, Gla, Ala, His, halo-His,
CA 02361534 2002-02-22
Arg, ornithine, homoarginine, Lys, N-methyl-Lys.
<220>
<221> PEPTIDE
<222> (19)..(21)
<223> Xaa at residue 19 is also N,N-dimethyl-Lys, N,N,N-
trimethyl-Lys or any unnatural basic amino acid; Xaa
at residue 21 is des-Xaa, Gly, Asp, Asn, Ala, Ile,
Leu, Ser, Thr, His, halo-His, Arg, ornithine.
<220>
<221> PEPTIDE
<222> (21)..(22)
<223> Xaa at residue 21 is also homoarginine, Lys, N-methyl-
Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any
unnatural basic amino acid; Xaa at residue 22 is
des-Xaa, Gly, Glu, Gla, Gln, Trp (D or L), neo-Trp.
<220>
<221> PEPTIDE
<222> (22)
<223> Xaa at residue 22 is also halo-Trp, any unnatural
aromatic amino acid, Arg,ornithine, homoarginine, Lys,
N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or
any unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (23)
<223> Xaa at residue 23 is des-Xaa, Ser, Thr, Val, Ile,
Ala, Arg, ornithine, homo-arginine, Lys, N-methyl-Lys,
N,N-dimethyl-Lys, N,N,N-trimethyl-Lys or any
unnatural basic amino acid.
<220>
<221> PEPTIDE
<222> (24)
<223> Xaa at residue 24 is des-Xaa, Val, Asp, His, halo-His,
Arg, ornithine, homoarginine, Lys, N-methyl-Lys, N,N-
dimethyl-Lys, N,N,N-trimethyl-Lys or any unnatural
basic amino acid.
<220>
<221> PEPTIDE
<222> (25)..(26)
<223> Xaa at residue 25 is des-Xaa, Asn, Pro or hydroxy-Pro;
Xaa at residue 26 is des-Xaa, Arg, ornithine, homo-
arginine, Lys, N-methyl-Lys, N,N-dimethyl-Lys.
<220>
<221> PEPTIDE
<222> (26)..(28)
<223> Xaa at residue 26 is also N,N,N-trimethyl-Lys or any
unnatural basic amino acid; Xaa at residue 27 is
des-Xaa, Ser or Thar; Xaa at residue 28 is des-Xaa,
Leu, Ile or Val.
CA 02361534 2002-02-22
11
<400> 3
Xaa Xaa Xaa Xaa Xaa Cys Cys Xaa Xaa Xaa Xaa Cys Xaa Xaa Xaa Xaa
1 5 10 15
Xaa Xaa Xaa Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25
<210> 4
<211> 14
<212> PRT
<213> Conus imperialis
<220>
<221> PEPTIDE
<222> (2)..(11)
<223> Xaa at residue 2 is Glu or gamma-carboxy-Glu; Xaa
at residue 11 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<400> 4
Asp Xaa Cys Cys Ser Asp Ser Arg Cys Gly Xaa Asn Cys Leu
1 5 10
<210> 5
<211> 12
<212> PRT
<213> Conus imperialis
<220>
<221> PEPTIDE
<222> (10)
<223> Xaa at residue 10 is Trp (D or L) or halo-Trp.
<400> 5
Ala Cys Cys Ser Asp Arg Arg Cys Arg Xaa Arg Cys
1 5 10
<210> 6
<211> 13
<212> PRT
<213> Conus regius
<400> 6
Phe Thr Cys Cys Arg Arg Gly Thr Cys Ser Gin His Cys
1 5 10
<210> 7
<211> 13
<212> PRT
<213> Conus regius
CA 02361534 2002-02-22
1.2
<220>
<221> PEPTIDE
<222> (2)
<223> Xaa at residue 2 :is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr.
<400> 7
Asp Xaa Cys Cys Arg Arg His Ala Cys Thr Leu Ile Cys
1 5 10
<210> 8
<211> 13
<212> PRT
<213> Conus regius
<220>
<221> PEPTIDE
<222> (2)..(8)
<223> Xaa at residue 2 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr or
nitro-Tyr; Xaa at residues 7 and 8 is Pro or
hydroxy-Pro.
<400> 8
Asp Xaa Cys Cys Arg Arg Xaa Xaa Cys Thr Leu Ile Cys
1 5 10
<210> 9
<211> 13
<212> PRT
<213> Conus regius
<220>
<221> PEPTIDE
<222> (6)..(10)
<223> Xaa at residue 6 is Pro or hdroxy-Pro; Xaa at
residue 10 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, 0-phospho-Tyr or
nitro-Tyr.
<400> 9
Gly Cys Cys Ser Asp Xaa Arg Cys Arg Xaa Arg Cys Arg
1 5 10
<210> 10
<211> 13
<212> PRT
<213> Conus regius
<220>
<221> PEPTIDE
CA 02361534 2002-02-22
1.3
<222> (7) (11)
<223> Xaa at residue 7 is Pro or hydroxy-Pro; Xaa at
residue 11 is Trp (D or L) or halo-Trp.
<400> 10
Gly Gly Cys Cys Ser Asp Xaa Arg Cys Ala Xaa Arg Cys
1 5 10
<210> 11
<211> 17
<212> PRT
<213> Conus regius
<220>
<221> PEPTIDE
<222> (3)..(10)
<223> Xaa at residue 3 is Trp (D or L) or halo-Trp; Xaa
at residue 9 is Glu or gamma-carboxy-Glu; Xaa at
residue 10 is Pro or hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (15)
<223> Xaa at residue 15 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl--Lys.
<400> 11
Ile Ala Xaa Asp Ile Cys Cys Ser Xaa Xaa Asp Cys Asn His Xaa Cys
1 5 10 15
Val
<210> 12
<211> 12
<212> PRT
<213> Conus regius
<220>
<221> PEPTIDE
<222> (6)..(9)
<223> Xaa at residue 6 is Pro or hydroxy-Pro; Xaa at
residue 9 is Lys, N-methyl-Lys, N,N-dimethyl.-Lys
or N,N,N-trimethyl.-Lys.
<400> 12
Gly Cys Cys Ser Asp Xaa Arg Cys Xaa His Gln Cys
1 5 10
<210> 13
<211> 14
<212> PRT
CA 02361534 2002-02-22
14
<213> Conus sponsalis
<220>
<221> PEPTIDE
<222> (5)..(11)
<223> Xaa at residues 5 and 11 is Pro or hydroxy-Pro;
Xaa at residue 8 is Lys, N-methyl-Lys,
N.N-dimethyl-Lys or N.N.n-trimethyl-Lys.
<400> 13
Cys Cys Ser Asp Xaa Ala Cys Xaa Gln Thr Xaa Gly Cys Arg
1 5 10
<210> 14
<211> 13
<212> PRT
<213> Conus sponsalis
<220>
<221> PEPTIDE
<222> (3) .. (5)
<223> Xaa at residue 3 is Glu or gamma-carboxy-Glu; Xaa
at residue 5 is Pro or hydroxy--Pro.
<400> 14
Cys Cys Xaa Asn Xaa Ala Cys Arg His Thr Gln Gly Cys
1 5 10
<210> 15
<211> 13
<212> PRT
<213> Conus sulcatus
<220>
<221> PEPTIDE
<222> (4)..(12)
<223> Xaa at residue 4 is Trp or halo-Trp; Xaa at
residue 6 is Pro or hydroxy-Pro; Xaa at residue 12
is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr,
0-sulpho-Tyr, 0-phospho-Tyr or nitro-Tyr.
<400> 15
Gly Cys Cys Xaa His Xaa Ala Cys Gly Arg His Xaa Cys
1 5 10
<210> 16
<211> 14
<212> PRT
<213> Conus achatinus
<220>
<221> PEPTIDE
CA 02361534 2002-02-22
<222> (2) .. (11)
<223> Xaa at residues 2 and 7 is Pro or hydroxy-Pro; Xaa
at residue 11 is Lys, N--methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<400> 16
Ala Xaa Cys Cys Asn Asn Xaa Ala Cys Val Xaa His Arg Cys
1 5 10
<210> 17
<211> 15
<212> PRT
<213> Conus bullatus
<220>
<221> PEPTIDE
<222> (2)..(12)
<223> Xaa at residues 2 and 8 is Pro or hydroxy-Pro; Xaa
at residue 12 is Lys, N-methyl--Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<400> 17
Ala Xaa Gly Cys Cys Asn Asn Xaa Ala Cys Val Xaa His Arg Cys
1 5 10 15
<210> 18
<211> 14
<212> PRT
<213> Conus bullatus
<220>
<221> PEPTIDE
<222> (1)..(11)
<223> Xaa at residues 1, 2 and 7 is Pro or hydroxy-Pro;
Xaa at residue 11 is Lys, N--methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<400> 18
Xaa Xaa Cys Cys Asn Asn Xaa Ala Cys Val Xaa His Arg Cys
1 5 10
<210> 19
<211> 16
<212> PRT
<213> Conus bullatus
<220>
<221> PEPTIDE
<222> (2)..(13)
<223> Xaa at residue 2 is Glu or gamma-carboxy-Glu; Xaa
at residue 6 is Trp or halo-Trp; Xaa at residues 8
11 and 13 is Pro or hydroxy-Pro.
CA 02361534 2002-02-22
16
<400> 19
Asp Xaa Asn Cys Cys Xaa Asn Xaa Ser Cys Xaa Arg Xaa Arg Cys Thr
1 5 10 15
<210> 20
<211> 13
<212> PRT
<213> Conus bullatus
<220>
<221> PEPTIDE
<222> (6) .. (12)
<223> Xaa at residues 6 and 7 is Pro or hydroxy-Pro; Xaa
at residue 12 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr.
<400> 20
Gly Cys Cys Ser Arg Xaa Xaa Cys Ala Val Leu Xaa Cys
1 5 10
<210> 21
<211> 13
<212> PRT
<213> Conus circumcisus
<220>
<221> PEPTIDE
<222> (6)
<223> Xaa at residue 6 is Pro or hydroxy-Pro.
<400> 21
Gly Cys Cys Gly Asn Xaa Asp Cys Thr Sear His Ser Cys
1 5 10
<210> 22
<211> 16
<212> PRT
<213> Conus stercusmuscarum
<220>
<221> PEPTIDE
<222> (6)..(11)
<223> Xaa at residue 6 is Pro or hydroxy-Pro; Xaa at
residue 11 is Glu or gamma-carboxy-Glu.
<400> 22
Gly Cys Cys Ser Asn Xaa Val. Cys His Leu Xaa His Ser Asn Met Cys
1 5 10 15
<210> 23
CA 02361534 2002-02-22
17
<211> 17
<212> PRT
<213> Conus obscurus
<220>
<221> PEPTIDE
<222> (6)..(15)
<223> Xaa at residue 6 is Pro or hydroxy-Pro; Xaa at
residue 14 is Glu or gamma-carboxy-Glu; Xaa at
residue 15 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr or
<220>
<221> PEPTIDE
<222> (15)
<223> nitro-Tyr.
<400> 23
Gly Cys Cys Ser Asn Xaa Val Cys Arg Gln Asn Asn Ala Xaa Xaa Cys
1 5 10 15
Arg
<210> 24
<211> 18
<212> PRT
<213> Conus textile
<220>
<221> PEPTIDE
<222> (1) .. (15)
<223> Xaa at residues 1, 7 and 14 is Pro or hydroxy-Pro;
Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 24
Xaa Gln Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Ile
1 5 10 15
Cys Arg
<210> 25
<211> 18
<212> PRT
<213> Conus radiatus
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Xaa at residues 1, 7 and 14 is Pro or hydroxy-Pro;
Xaa at residues 2 and 15 is Glu or
gamma-carboxy-Glu.
CA 02361534 2002-02-22
18
<400> 25
Xaa Xaa Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Ile
1 5 10 15
Cys Arg
<210> 26
<211> 18
<212> PRT
<213> Conus radiatus
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Xaa at residues 1, 7 and 14 is Pro or hydroxy-Pro;
Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 26
Xaa Gln Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Ile
1 5 10 15
Cys Asp
<210> 27
<211> 18
<212> PRT
<213> Conus omaria
<220>
<221> PEPTIDE
<222> (1) .. (15)
<223> Xaa at residues 1, 7 and 14 is Pro or hydroxy-Pro;
Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 27
Xaa Arg Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Ile
1 5 10 15
Cys Arg
<210> 28
<211> 18
<212> PRT
<213> Conus omaria
<220>
<221> PEPTIDE
<222> (1) .. (14)
<223> Xaa at residues 1, 7 and 14 is Pro or hydroxy-Pro.
CA 02361534 2002-02-22
19
<400> 28
Xaa Gln Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Gly Ile
1 5 10 15
Cys Arg
<210> 29
<211> 18
<212> PRT
<213> Conus omaria
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Xaa at residues 1, 7 and 14 is Pro or hydroxy-Pro;
Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 29
Xaa Gln Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Thr
1 5 10 15
Cys Arg
<210> 30
<211> 18
<212> PRT
<213> Conus omaria
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Xaa at residues 1, 7 and 14 is Pro or hydroxy-Pro;
Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 30
Xaa Gln Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Val
1 5 10 15
Cys Arg
<210> 31
<211> 18
<212> PRT
<213> Conus omaria
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Xaa at residues 1, 7 and 14 is Pro or hydroxy-Pro;
CA 02361534 2002-02-22
Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 31
Xaa Gln Cys Cys Ser His Xaa Ala Cys Asn Ile Asp His Xaa Xaa Ile
1 5 10 15
Cys Arg
<210> 32
<211> 21
<212> PRT
<213> Conus omaria
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Xaa at residues 1, 7 and 14 is Pro or hydroxy-Pro;
Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 32
Xaa Gln Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Ile
1 5 10 15
Cys Arg Arg Arg Arg
<210> 33
<211> 17
<212> PRT
<213> Conus betulinus
<220>
<221> PEPTIDE
<222> (7)..(15)
<223> Xaa at residues 7 and 14 is Pro or hydroxy-Pro;
Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 33
Gly Gly Cys Cys Ser His Xaa Ala Cys Ala Val Asn His Xaa Xaa Leu
1 5 10 15
Cys
<210> 34
<211> 16
<212> PRT
<213> Conus betulinus
<220>
<221> PEPTIDE
<222> (6)..(14)
CA 02361534 2002-02-22
21
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 14 is Glu or gamma-carboxy-Glu.
<400> 34
Gly Cys Cys Ser His Xaa Ala Cys Ser Val Asn His Xaa Xaa Leu Cys
1 5 10 15
<210> 35
<211> 16
<212> PRT
<213> Conus dalli
<220>
<221> PEPTIDE
<222> (6) .. (14)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 14 is Glu or gamma-carboxy-Gl.u.
<400> 35
Gly Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Ile Cys
1 5 10 15
<210> 36
<211> 19
<212> PRT
<213> Conus obscurus
<220>
<221> PEPTIDE
<222> (6)..(18)
<223> Xaa at residues 6 and 15 is Pro or hydroxy-Pro;
Xaa at reside 11 is Lys, N,-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa at
residues 14 and 18 is Glu or gamma-carboxy-Glu.
<400> 36
Gly Cys Cys Ser His Xaa Ala Cys Ser Gly Xaa Thr Gln Xaa Xaa Cys
1 5 10 15
Arg Xaa Ser
<210> 37
<211> 18
<212> PRT
<213> Conus tulipa
<220>
<221> PEPTIDE
<222> (1)..(14)
<223> Xaa at residues 1, 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 14 is Glu or gamma-carboxy-Glu.
CA 02361534 2002-02-22
22
<400> 37
Xaa Cys Cys Ser His Xaa Ala Cys Ser Gly Asn Asn Xaa Xaa Phe Cys
1 5 10 15
Arg Gln
<210> 38
<211> 18
<212> PRT
<213> Conus tulipa
<220>
<221> PEPTIDE
<222> (6)..(14)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 14 is Glu or gamma-carboxy-Glu.
<400> 38
Gly Cys Cys Ser His Xaa Ala Cys Ser Gly Asn Asn Xaa Xaa Phe Cys
1 5 10 15
Arg Gln
<210> 39
<211> 16
<212> PRT
<213> Conus pennaceus
<220>
<221> PEPTIDE
<222> (6)..(15)
<223> Xaa at residues 6, 7 and 13 is Pro or hydroxy-Pro;
Xaa at residue 15 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr or
nitro-Tyr.
<400> 39
Gly Cys Cys Ser His Xaa Xaa Cys Ala Met Asn Asn Xaa Asp Xaa Cys
1 5 10 15
<210> 40
<211> 16
<212> PRT
<213> Conus pennaceus
<220>
<221> PEPTIDE
<222> (6)..(15)
<223> Xaa at residuew 6, 7 and 13 is Pro or hydroxy-Pro;
Xaa at residue 15 is Tyr, nor-Tyr, mono-halo-Tyr,
CA 02361534 2002-02-22
23
di-halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr or
nitro-Tyr.
<400> 40
Gly Cys Cys Ser His Xaa Xaa Cys Phe Leu Asn Asn Xaa Asp Xaa Cys
1 5 10 15
<210> 41
<211> 17
<212> PRT
<213> Conus textile
<220>
<221> PEPTIDE
<222> (6) .. (13)
<223> Xaa at residues 6, 7 and 13 is Pro or hydroxy-Pro;
Xaa at residue 11 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N.N.N-trimethyl-Lys.
<400> 41
Gly Cys Cys Ser Asn Xaa Xaa Cys Ile Ala Xaa Asn Xaa His Met Cys
1 5 10 15
Gly
<210> 42
<211> 16
<212> PRT
<213> Conus distans
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6, 7 and 13 is Pro or hydroxy-Pro.
<400> 42
Gly Cys Cys Ser Asn Xaa Xaa Cys Ala His Asn Asn Xaa Asp Cys Arg
1 5 10 15
<210> 43
<211> 17
<212> PRT
<213> Conus tulipa
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
<400> 43
Gly Cys Cys Ser Asn Xaa Ala Cys Ala Gly Asn Asn Xaa His Val Cys
1 5 10 15
CA 02361534 2002-02-22
24
Arg
<210> 44
<211> 16
<212> PRT
<213> Conus dalli
<220>
<221> PEPTIDE
<222> (6) .. (13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
<400> 44
Gly Cys Cys Ser Arg Xaa Ala Cys Ile Ala Asn Asn Xaa Asp Leu Cys
1 5 10 15
<210> 45
<211> 20
<212> PRT
<213> Conus circumcisus
<220>
<221> PEPTIDE
<222> (6)..(14)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residues 11 and 14 is Glu or
gamma-carboxy-Glu.
<400> 45
Gly Cys Cys Ser Asn Xaa Val Cys His Val Xaa His Xaa Xaa Leu Cys
1 5 10 15
Arg Arg Arg Arg
<210> 46
<211> 18
<212> PRT
<213> Conus sulcatus
<220>
<221> PEPTIDE
<222> (7)..(14)
<223> Xaa at residues 7, 17.2 and 14 is Pro or
hydroxy-Pro; Xaa at residue 11 is Lys,
N-methyl-Lys, N,N-dimethyl-Lys or
N,N,N-trimethyl-Lys.
<220>
CA 02361534 2002-02-22
<221> PEPTIDE
<222> (15)
<223> Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 46
Gly Gly Cys Cys Ser Phe Xaa Ala Cys Arg Xaa Xaa Arg Xaa Xaa Met
1 5 10 15
Cys Gly
<210> 47
<211> 18
<212> PRT
<213> Conus textile
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Xaa at residues 1, 7 and 14 is Pro or hydroxy-Pro;
Xaa at residues 2 and 15 is Glu or
gamma-carboxy-Glu..
<400> 47
Xaa Xaa Cys Cys Ser Asp Xaa Arg Cys Asn Ser Ser His Xaa Xaa Leu
1 5 10 15
Cys Arg
<210> 48
<211> 18
<212> PRT
<213> Conus dalli
<220>
<221> PEPTIDE
<222> (1) .. (15)
<223> Xaa at residues 1, 7 and 14 is Pro or hydroxy-pro;
Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 48
Xaa Gln Cys Cys Ser Asp Xaa Arg Cys Asn Val Gly His Xaa Xaa Leu
1 5 10 15
Cys Gly
<210> 49
<211> 18
<212> PRT
<213> Conus dalli
CA 02361534 2002-02-22
26
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Xaa at residue 1 Is Gln or pyro-Glu; Xaa at
residues 7 and 14 is Pro or hydroxy--Pro; Xaa at
residue 15 is Glu or gamma-carboxy-Glu.
<400> 49
Xaa Val Cys Cys Ser Asp Xaa Arg Cys Asn Val Gly His Xaa Xaa Ile
1 5 10 15
Cys Gly
<210> 50
<211> 16
<212> PRT
<213> Conus textile
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6, 7 and 13 is Pro or hydroxy-Pro.
<400> 50
Gly Cys Cys Ser Arg Xaa Xaa Cys Ile Ala Asn Asn Xaa Asp Leu Cys
1 5 10 15
<210> 51
<211> 18
<212> PRT
<213> Conus omaria
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Xaa at residues 1 and 14 is Pro or hydroxy-Pro;
Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 51
Xaa Gln Cys Cys Ser His Leu Ala Cys Asn Val Asp His Xaa Xaa Ile
1 5 10 15
Cys Arg
<210> 52
<211> 19
<212> PRT
<213> Conus sulcatus
<220>
<221> PEPTIDE
CA 02361534 2002-02-22
27
<222> (5)..(13)
<223> Xaa at residue 5 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sul.pho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residue 13 is Pro or
hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (14)..(18)
<223> Xaa at residue 14 is Glu or gamma-carboxy-Glu; Xaa at
residue 18 is Trp or halo-Trp.
<400> 52
Gly Cys Cys Ser Xaa Phe Asp Cys Arg Met Met Phe Xaa Xaa Met Cys
1 5 10 15
Gly Xaa Arg
<210> 53
<211> 18
<212> PRT
<213> Conus sulcatus
<220>
<221> PEPTIDE
<222> (11)..(12)
<223> Xaa at residue 11 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa at
residue 12 is Tyr, nor-Tyr, mono-halo-Tyr, di-
halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr.
<220>
<221> PEPTIDE
<222> (14)..(15)
<223> Xaa at residue 14 is Pro or hydroxy-Pro; Xaa at
residue 15 is Glu or gamma-carboxy-Glu.
<400> 53
Gly Gly Cys Cys Ser Phe Ala Ala Cys Arg Xaa Xaa Arg Xaa Xaa Met
1 5 10 15
Cys Gly
<210> 54
<211> 20
<212> PRT
<213> Conus sulcatus
<220>
<221> PEPTIDE
CA 02361534 2002-02-22
28
<222> (7) (10)
<223> Xaa at residue 7 is Pro or hydroxy-Pro; Xaa at
residue 10 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr or
nitro-Tyr.
<220>
<221> PEPTIDE
<222> (15)
<223> Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 54
Gly Gly Cys Cys Phe His Xaa Val Cys Xaa Ile Asn Leu Leu Xaa Met
1 5 10 15
Cys Arg Gln Arg
<210> 55
<211> 19
<212> PRT
<213> Conus betulinus
<220>
<221> PEPTIDE
<222> (7)..(15)
<223> Xaa at residues 7, 11. and 1.4 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, 0-sulpho-Tyr,
0-phospho-Tyr; Xaa at residues 8, 9 and 15 is Pro
or hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (12)..(16)
<223> Xaa at residues 12 and 16 is Glu or
gamma-carboxy-Glu.
<400> 55
Ser Ala Thr Cys Cys Asn Xaa Xaa Xaa Cys Xaa Xaa Thr Xaa Xaa Xaa
1 5 10 15
Ser Cys Leu
<210> 56
<211> 17
<212> PRT
<213> Conus betulinus
<220>
<221> PEPTIDE
<222> (5)..(13)
<223> Xaa at residues 5 and 12 is Tyr, no-Tyr,
CA 02361534 2002-02-22
29
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr,
0-phospho-Tyr or nitro-Tyr; Xaa at residues 6, 7
and 13 is Pro or hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (10)..(14)
<223> Xaa at residues 10 and 14 is Glu or
gamma-carboxy-Glu.
<400> 56
Ala Cys Cys Ala Xaa Xaa Xaa Cys Phe Xaa Ala Xaa Xaa Xaa Arg Cys
1 5 10 15
Leu
<210> 57
<211> 19
<212> PRT
<213> Conus betulinus
<220>
<221> PEPTIDE
<222> (3)..(16)
<223> Xaa at residues 3, 12 and 16 is Glu or
gamma-carboxy-Glu; Xaa at residues 6, 7, 11 and 14
is Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr.
<220>
<221> PEPTIDE
<222> (8)..(15)
<223> Xaa at residues 8, 9 and 15 is Pro or hydroxy-Pro.
<400> 57
Asn Ala Xaa Cys Cys Xaa Xaa Xaa Xaa Cys Xaa Xaa Ala Xaa Xaa Xaa
1 5 10 15
Ile Cys Leu
<210> 58
<211> 227
<212> DNA
<213> Conus magus
<220>
<221> CDS
<222> (1)..(189)
<400> 58
CA 02361534 2002-02-22
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Levu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac gac 96
Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp
20 25 30
aaa gcg tct gac gtg atc acg ctg gcc ctc aag gga tgc tgt tcc aac 144
Lys Ala Ser Asp Val Ile Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn
40 45
cct gtc tgt cac ttg gag cat tca aac ctt tgt ggt aga aga cgc 189
Pro Val Cys His Leu Glu His Ser Asn Leu Cys Gly Arg Arg Arg
50 55 60
tgatgctcca ggaccctctg aaccacgacg ttcgagca 227
<210> 59
<211> 63
<212> PRT
<213> Conus magus
<400> 59
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp
20 25 30
Lys Ala Ser Asp Val Ile Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn
35 40 45
Pro Val Cys His Leu Glu His Ser Asn Le.u Cys Gly Arg Arg Arg
50 55 60
<210> 60
<211> 208
<212> DNA
<213> Conus aulicus
<220>
<221> CDS
<222> (1)..(168)
<400> 60
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca gat cgt gca tct gat ggc agg aag gac gca gcg tct ggc 96
Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Lys Asp Ala Ala Ser Gly
20 25 30
CA 02361534 2002-02-22
31
ctg atc get ctg acc atc aag gga tgc tgt tct tat cct ccc tgt ttc 144
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe
35 40 45
gcg act aat tca gac tat tgt ggt tgacgacgct gatgctccag gaccctctga 198
Ala Thr Asn Ser Asp Tyr Cys Gly
50 55
accacgacgt 208
<210> 61
<211> 56
<212> PRT
<213> Conus aulicus
<400> 61
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Lys Asp Ala Ala Ser Gly
20 25 30
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe
35 40 45
Ala Thr Asn Ser Asp Tyr Cys Gly
50 5 5
<210> 62
<211> 205
<212> DNA
<213> Conus aulicus
<220>
<221> CDS
<222> (1)..(174)
<400> 62
atg ttc acc gtg ttt ctg ttg gtc gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca gat cgt gca tct gat ggc agg aag gac gca gcg tct ggc 96
Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Lys Asp Ala Ala Ser Gly
20 25 30
ctg att get ctg acc atg aag gga tgc tgt tct tat cct ccc tgt ttc 144
Leu Ile Ala Leu Thr Met Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe
35 40 45
gcg act aat cca gac tgt ggt cga cga cgc tgatgctcca ggaccctctg 194
Ala Thr Asn Pro Asp Cys Gly Arg Arg Arg
50 55
CA 02361534 2002-02-22
32
aaccacgacg t 205
<210> 63
<211> 58
<212> PRT
<213> Conus aulicus
<400> 63
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Lys Asp Ala Ala Ser Gly
20 25 30
Leu Ile Ala Leu Thr Met Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe
35 40 45
Ala Thr Asn Pro Asp Cys Gly Arg Arg Arg
50 55
<210> 64
<211> 223
<212> DNA
<213> Conus textile
<220>
<221> CDS
<222> (1)..(192)
<400> 64
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc tct tca ggt cgt agt aca ttt cgt ggc agg aat gcc gca gcc aaa 96
Phe Ser Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys
20 25 30
gcg tct ggc ctg gtc agt ctg act gac agg aga cca gaa tgc tgt agt 144
Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser
35 40 45
gat cct cgc tgt aac tcg agt cat cca gaa ctt tgt ggt gga aga cgc 192
Asp Pro Arg Cys Asn Ser Ser His Pro Glu Leu Cys Gly Gly Arg Arg
50 55 60
tgatgctcca ggaccctctg aaccacgacg t 223
<210> 65
<211> 64
<212> PRT
<213> Conus textile
CA 02361534 2002-02-22
33
<400> 65
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Ser Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys
20 25 30
Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser
35 40 45
Asp Pro Arg Cys Asn Ser Ser His Pro Glu Leu Cys Gly Gly Arg Arg
50 J5 60
<210> 66
<211> 244
<212> DNA
<213> Conus textile
<220>
<221> CDS
<222> (1)..(168)
<400> 66
atg ttc acc gtg ttt ctg tt:g gtt gtc ttg gca acc gcc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Ala Val Val Ser
1 5 10 15
ttc act tca gat cgt gca tct gat gac ggg aaa gcc get gcg tct gac 96
Phe Thr Ser Asp Arg Ala Ser Asp Asp Gly Lys Ala Ala Ala Ser Asp
20 25 30
ctg atc act ctg acc atc aag gga tgc tgt tct cgt cct ccc tgt atc 144
Leu Ile Thr Leu Thr Ile Lys Gly Cys Cys Ser Arg Pro Pro Cys Ile
35 40 45
gcg aat aat cca gac ttg tgt ggt tgacgacgct gatgctccag aacggtctga 198
Ala Asn Asn Pro Asp Leu Cys Gly
50 55
accacgacgt tcgagcaatg ttcaccgtgt ttctgttggt tgtctt. 244
<210> 67
<211> 56
<212> PRT
<213> Conus textile
<400> 67
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Ala Val Val Ser
1 5 10 15
Phe Thr Ser Asp Arg Ala Ser Asp Asp Gly Lys Ala Ala Ala Ser Asp
20 25 30
Leu Ile Thr Leu Thr Ile Lys Gly Cys Cys Ser Arg Pro Pro Cys Ile
35 40 45
CA 02361534 2002-02-22
34
Ala Asn Asn Pro Asp Leu Cys Gly
50 55
<210> 68
<211> 223
<212> DNA
<213> Conus textile
<220>
<221> CDS
<222> (1)..(183)
<400> 68
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca ggt cgt agt aca ttt cgt ggc agg aat gcc gca gcc aaa 96
Phe Thr Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys
20 25 30
gcg tct ggc ctg gtc agt ctg act gac agg aga cca caa tgc tgt tct 144
Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser
35 40 45
cat cct gcc tgt aac gta gat cat cca gaa att tgt cgt tgaagacgct 193
His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Arg
50 55 60
gatgctccag gaccctctga accacgacgt 223
<210> 69
<211> 61
<212> PRT
<213> Conus textile
<400> 69
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys
20 25 30
Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser
35 40 45
His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Arg
50 55 60
<210> 70
CA 02361534 2002-02-22
<211> 223
<212> DNA
<213> Conus radiatus
<220>
<221> CDS
<222> (1)..(183)
<400> 70
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca ggt cgt cgt aca ttt cat ggc agg aat gcc gca gcc aaa 96
Phe Thr Ser Gly Arg Arg Thr Phe His Gly A2:.-g' Asn Ala Ala Ala Lys
20 25 30
gcg tct ggc ctg gtc agt ctg act gac agg aga cca gaa tgc tgt tct 144
Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser
35 40 45
cat cct gcc tgt aac gta gat cat cca gaa att tgt cgt tgaagacgct 193
His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Arg
50 55 60
gatgctccag gaccctctga accacgacgt 223
<210> 71
<211> 61
<212> PRT
<213> Conus radiatus
<400> 71
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Gly Arg Arg Thr Phe His Gly Arg Asn Ala Ala Ala Lys
20 25 30
Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser
35 40 45
His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Arg
50 55 60
<210> 72
<211> 223
<212> DNA
<213> Conus radiatus
<220>
<221> CDS
<222> (1)..(183)
CA 02361534 2002-02-22
36
<400> 72
atg ttc acc gtg ttt ctg tt:g gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca ggt cgt agt aca ttt cgt ggc agg aat gcc gca gcc aaa 96
Phe Thr Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys
20 25 30
gcg tct ggc ctg gtc agt ct:g act gac agg aga cca caa tgc tgt tct 144
Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser
35 40 45
cat cct gcc tgt aac gta gat cat cca gaa att tgc gat tgaagacgct 193
His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Asp
50 55 60
gatgctccag gaccctctga accacgacgt 223
<210> 73
<211> 61
<212> PRT
<213> Conus radiatus
<400> 73
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Gly Arg Ser Thr Phe Arg Gly Arg Asn Ala Ala Ala Lys
20 25 30
Ala Ser Gly Leu Val Ser Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser
35 40 45
His Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Asp
50 55 60
<210> 74
<211> 218
<212> DNA
<213> Conus striatus
<220>
<221> CDS
<222> (1)..(171)
<400> 74
atg ttc act gtg ttt ctg ttg gtt gtc ttg gca atc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Ile Thr Val Val Ser
1 5 10 15
ttc cct tta gat cgt gaa tct gat ggc gcg aat gcc gaa gcc cgc acc 96
Phe Pro Leu Asp Arg Glu Ser Asp Gly Ala Asn Ala Glu Ala Arg Thr
20 25 30
CA 02361534 2002-02-22
37
cac gat cat gag aag cac gca ctg gac cgg aat gga tgc tgt agg aat 144
His Asp His Glu Lys His Ala Leu Asp Arg Asn Gly Cys Cys Arg Asn
35 40 45
cct gcc tgt gag agc cac aga tgt ggt tgacgacgct gatgctccag 191
Pro Ala Cys Glu Ser His A:rg Cys Gly
50 55
gaccctctga accacgacgt tcgagca 218
<210> 75
<211> 57
<212> PRT
<213> Conus striatus
<400> 75
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Ile Thr Val Val Ser
1 5 10 15
Phe Pro Leu Asp Arg Glu Ser Asp Gly Ala Asn Ala Glu Ala Arg Thr
20 25 30
His Asp His Glu Lys His Ala Leu Asp Arg Asn Gly Cys Cys Arg Asn
35 40 45
Pro Ala Cys Glu Ser His Arg Cys Gly
50 5 5
<210> 76
<211> 227
<212> DNA
<213> Conus bandanus
<220>
<221> CDS
<222> (1)..(180)
<400> 76
atg ttc acc atg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Met Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc get tca gat cgt gca tct gat ggc agg aat. gcc gca gcc aag gac 96
Phe Ala Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp
20 25 30
aaa gcg tct gac ctg gtc get ctg acc gtc aag gga tgc tgt tct cat 144
Lys Ala Ser Asp Leu Val Ala Leu Thr Val Lys Gly Cys Cys Ser His
35 40 45
cct gcc tgt agc gtg aat aat cca gac att tgt ggt tgaagacgct 190
Pro Ala Cys Ser Val Asn Asn Pro Asp Ile Cys Gly
50 55 60
CA 02361534 2002-02-22
38
gatgctccag gaccctctga accacgacgt tcgagca 227
<210> 77
<211> 60
<212> PRT
<213> Conus bandanus
<400> 77
Met Phe Thr Met Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Ala Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp
20 25 30
Lys Ala Ser Asp Leu Val Ala Leu Thr Val Lys Gly Cys Cys Ser His
35 40 45
Pro Ala Cys Ser Val Asn Asn Pro Asp Ile Cys Gly
50 55 60
<210> 78
<211> 104
<212> DNA
<213> Conus bandanus
<220>
<221> CDS
<222> (1)..(54)
<400> 78
aaa gaa tgc tgt act cat cct gcc tgt cac gtg agt cat cca gaa ctc 48
Lys Glu Cys Cys Thr His Pro Ala Cys His Val Ser His Pro Glu Leu
1 5 10 15
tgt ggt tgaaaagcga cgtgacgctc caggaccctc tgaaccacga cgttcgagca 104
Cys Gly
<210> 79
<211> 18
<212> PRT
<213> Conus bandanus
<400> 79
Lys Glu Cys Cys Thr His Pro Ala Cys His Val Ser His Pro Glu Leu
1 5 10 15
Cys Gly
CA 02361534 2002-02-22
39
<210> 80
<211> 206
<212> DNA
<213> Conus bandanus
<220>
<221> CDS
<222> (1)..(171)
<400> 80
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca act get gtt ctt cca 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Ala Val Leu Pro
1 5 10 15
gtc act tta gat cgt gca tct gat gga agg aat gca gca gcc aac gcc 96
Val Thr Leu Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala
20 25 30
aaa acg cct cgc ctg atc gcg cca ttc atc agg gat tat tgc tgt cat 144
Lys Thr Pro Arg Leu Ile Ala Pro Phe Ile Arg Asp Tyr Cys Cys His
35 40 45
aga ggt ccc tgt atg gta tgg tgt ggt tgaagccgct gctgctccag 191
Arg Gly Pro Cys Met Val Trp Cys Gly
50 55
gaccctctga accac 206
<210> 81
<211> 57
<212> PRT
<213> Conus bandanus
<400> 81
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Ala Val Leu Pro
1 5 10 15
Val Thr Leu Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala
20 25 30
Lys Thr Pro Arg Leu Ile Ala Pro Phe Ile Arg Asp Tyr Cys Cys His
35 40 45
Arg Gly Pro Cys Met Val Trp Cys Gly
50 55
<210> 82
<211> 174
<212> DNA
<213> Conus caracteristicus
<220>
<221> CDS
CA 02361534 2002-02-22
<222> (1)..(171)
<400> 82
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtg gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca gat cgt get tct gat ggc agg aat gcc gca gcc aac gcg 96
Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala
20 25 30
ttt gac ctg atc get ctg atc gcc agg caa aat tgc tgt agc att ccc 144
Phe Asp Leu Ile Ala Leu Ile Ala Arg Gln Asn Cys Cys Ser Ile Pro
35 40 45
agc tgt tgg gag aaa tat aaa tgt agt taa 174
Ser Cys Trp Glu Lys Tyr Lys Cys Ser
`55
<210> 83
<211> 57
<212> PRT
<213> Conus caracteristicus
<400> 83
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala
20 25 30
Phe Asp Leu Ile Ala Leu Ile Ala Arg Gln Asn Cys Cys Ser Ile Pro
35 40 45
Ser Cys Trp Glu Lys Tyr Lys Cys Ser
<210> 84
<211> 219
<212> DNA
<213> Conus caracteristicus
<220>
<221> CDS
<222> (1)..(189)
<400> 84
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtg gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val. Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca gat cgt gcg tct gaa ggc agg aat get gca gcc aag gac 96
Phe Thr Ser Asp Arg Ala Ser Glu Gly Arg Asn Ala Ala Ala Lys Asp
20 25 30
CA 02361534 2002-02-22
41
aaa gcg tct gac ctg gtg get ctg aca gtc agg gga tgc tgt gcc att 144
Lys Ala Ser Asp Leu Val Ala Leu Thr Val Arg Gly Cys Cys Ala Ile
35 40 45
cgt gaa tgt cgc ttg cag aat gca gcg tat tgt ggt gga ata tac 189
Arg Glu Cys Arg Leu Gln A.sn Ala Ala Tyr Cys Gly Gly Ile Tyr
50 55 60
tgatgctcca ggaccctctg aaccacgacg 219
<210> 85
<211> 63
<212> PRT
<213> Conus caracteristicus
<400> 85
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Asp Arg Ala Ser. Glu Gly Arg Asn Ala Ala Ala Lys Asp
20 25 30
Lys Ala Ser Asp Leu Val Ala Leu Thr Val Arg Gly Cys Cys Ala Ile
35 40 45
Arg Glu Cys Arg Leu Gln Asn Ala Ala Tyr Cys Gly Gly Ile Tyr
50 E3 F, 60
<210> 86
<211> 217
<212> DNA
<213> Conus tulipa
<220>
<221> CDS
<222> (1)..(186)
<400> 86
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc cct tca gat att gca act gag ggc agg aat gcc gca gcc aaa gcg 96
Phe Pro Ser Asp Ile Ala Thr Glu Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
ttt gac ctg ata tct tcg at:c gtc aag aaa gga tgc tgt tcc cat cct 144
Phe Asp Leu Ile Ser Ser Ile Val Lys Lys Gly Cys Cys Ser His Pro
35 40 45
gcc tgt tcg ggg aat aat cca gaa ttt tgt cgt caa ggt cgc 186
Ala Cys Ser Gly Asn Asn Piro Glu Phe Cys Arg Gin Gly Arg
50 `_>5 60
CA 02361534 2002-02-22
42
tgatgctcca ggaccctctg aaccacgacg t 217
<210> 87
<211> 62
<212> PRT
<213> Conus tulipa
<400> 87
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Pro Ser Asp Ile Ala Thr Glu Gly Arg An Ala Ala Ala Lys Ala
20 25 30
Phe Asp Leu Ile Ser Ser Ile Val Lys Lys Gly Cys Cys Ser His Pro
35 40 45
Ala Cys Ser Gly Asn Asn Pro Glu Phe Cys Arg Gln Gly Arg
50 55 60
<210> 88
<211> 217
<212> DNA
<213> Conus tulipa
<220>
<221> CDS
<222> (1)..(186)
<400> 88
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc cct tca gat ata gca act gag ggc agg aat gcc gca gcc aaa gcg 96
Phe Pro Ser Asp Ile Ala Thr Glu Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
ttt gac ctg ata tct tcg atc gtc agg aaa gga tgc tgt tcc aat ccc 144
Phe Asp Leu Ile Ser Ser Ile Val Arg Lys Gly Cys Cys Ser Asn Pro
35 40 45
gcc tgt gcg ggg aat aat cca cat gtt tgt cgt caa ggt cgc 186
Ala Cys Ala Gly Asn Asn Pro His Val Cys Arg Gln Gly Arg
50 55 60
tgatgctcca ggaccctctg aaccacgacg t 217
<210> 89
<211> 62
CA 02361534 2002-02-22
43
<212> PRT
<213> Conus tulipa
<400> 89
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Pro Ser Asp Ile Ala Thr Glu Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
Phe Asp Leu Ile Ser Ser Ile Val Arg Lys Gly Cys Cys Ser Asn Pro
35 40 45
Ala Cys Ala Gly Asn Asn Pro His Val Cys Arg Gln Gly Arg
50 55 60
<210> 90
<211> 226
<212> DNA
<213> Conus sulcatus
<220>
<221> CDS
<222> (1)..(195)
<400> 90
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc aat tca gat cgt gat cca gca tta ggt ggc agg aat get gca gcc 96
Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala
20 25 30
aaa gcg tct gac aag atc gct tcg acc ctc aag aga aga gga tgc tgt 144
Lys Ala Ser Asp Lys Ile Ala Ser Thr Leu Lys Arg Arg Gly Cys Cys
35 40 45
tcg tat ttt gac tgt aga atg atg ttt cca gaa atg tgt ggt tgg cga 192
Ser Tyr Phe Asp Cys Arg Met Met Phe Pro Glu Met Cys Gly Trp Arg
50 55 60
ggc tgatgctcca ggaccctct.g aaccacgacg t 226
Gly
<210> 91
<211> 65
<212> PRT
<213> Conus sulcatus
<400> 91
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
CA 02361534 2002-02-22
44
Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala
20 25 30
Lys Ala Ser Asp Lys Ile Ala Ser Thr Leu Lys Arg Arg Gly Cys Cys
35 40 45
Ser Tyr Phe Asp Cys Arg Met Met Phe Pro Glu Met Cys Gly Trp Arg
50 55 60
Gly
<210> 92
<211> 226
<212> DNA
<213> Conus sulcatus
<220>
<221> CDS
<222> (1)..(195)
<400> 92
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc aat tca gat cgt gat cca gca tta ggt ggc agg aat get gca gcc 96
Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala
20 25 30
ata gcg tct gac aag atc get tcg acc ctc agg aga gga gga tgc tgt 144
Ile Ala Ser Asp Lys Ile Ala Ser Thr Leu Arg Arg Gly Gly Cys Cys
35 40 45
tct ttt cct gcc tgt aga aag tat cgt cca gaa atg tgt ggt gga cga 192
Ser Phe Pro Ala Cys Arg Lys Tyr Arg Pro Glu Met Cys Gly Gly Arg
50 55 60
cgc tgatgctcca ggaccctctg aaccacgacg t 226
Arg
<210> 93
<211> 65
<212> PRT
<213> Conus sulcatus
<400> 93
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala
20 25 30
CA 02361534 2002-02-22
Ile Ala Ser Asp Lys Ile Ala Ser Thr Leu Arg Arg Gly Gly Cys Cys
35 40 45
Ser Phe Pro Ala Cys Arg Lys Tyr Arg Pro Glu Met Cys Gly Gly Arg
55 60
Arg
<210> 94
<211> 211
<212> DNA
<213> Conus sulcatus
<220>
<221> CDS
<222> (1)..(180)
<400> 94
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca gat cat gaa tct gat cgc ggt gat gcc caa acc atc caa 96
Phe Thr Ser Asp His Glu Ser Asp Arg Gly Asp Ala Gln Thr Ile Gln
20 25 30
gaa gtg ttt gag atg ttc get ctg gac agc gat gga tgc tgt tgg cat 144
Glu Val Phe Glu Met Phe Ala Leu Asp Ser Asp Gly Cys Cys Trp His
35 40 45
cct get tgt ggc aga cac tat tgt ggt cga aga cgc tgatgctcca 190
Pro Ala Cys Gly Arg His Tyr Cys Gly Arg Arg Arg
50 55 60
ggaccctctg aaccacgacg t 211
<210> 95
<211> 60
<212> PRT
<213> Conus sulcatus
<400> 95
Met Phe Thr Val Phe Leu Leu Val Val Leu A:La Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Asp His Glu Ser Asp Arg Gly Asp Ala Gln Thr Ile Gln
20 25 30
Glu Val Phe Glu Met Phe Ala Leu Asp Ser Asp Gly Cys Cys Trp His
35 40 45
CA 02361534 2002-02-22
46
Pro Ala Cys Gly Arg His Tyr Cys Gly Arg Arg Arg
50 55 60
<210> 96
<211> 202
<212> DNA
<213> Conus sulcatus
<220>
<221> CDS
<222> (1)..(195)
<400> 96
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc aat tca gat cgt gat cca gca tta ggt ggc agg aat get gca gcc 96
Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arq Asn Ala Ala Ala
20 25 30
ata gcg tct gac aag atc get tcg acc ctc agg aga gga gga tgc tgt 144
Ile Ala Ser Asp Lys Ile Ala Ser Thr Leu Arg Arg Gly Gly Cys Cys
35 40 45
tct ttt get gcc tgt aga aag tat cgt cca gaa atg tgt ggt gga cga 192
Ser Phe Ala Ala Cys Arg Lys Tyr Arg Pro Glu Met Cys Gly Gly Arg
50 55 60
cgc tgatgct 202
Arg
<210> 97
<211> 65
<212> PRT
<213> Conus sulcatus
<400> 97
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Asn Ser Asp Arg Asp Pro Ala Leu Gly Gly Arg Asn Ala Ala Ala
20 25 30
Ile Ala Ser Asp Lys Ile Ala Ser Thr Leu Arg Arg Gly Gly Cys Cys
35 40 45
Ser Phe Ala Ala Cys Arg Lys Tyr Arg Pro Glu Met Cys Gly Gly Arg
50 55 60
Arg
CA 02361534 2002-02-22
47
<210> 98
<211> 220
<212> DNA
<213> Conus sulcatus
<220>
<221> CDS
<222> (1)..(189)
<400> 98
atg ttc acc gtg ttt ctg ttg gtt ctc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Leu Leu Ala Thr Thr Val Val Ser
1 5 1.0 15
ttc aat tca gat cgt gca tta ggt ggc agg aat get gca gcc aaa gcg 96
Phe Asn Ser Asp Arg Ala Leu Gly Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
tct gac aag atc ctt tcg aac ctc agg aga gga gga tgc tgt ttt cat 144
Ser Asp Lys Ile Leu Ser Asn Leu Arg Arg Gly Gly Cys Cys Phe His
35 40 45
cct gtc tgt tac atc aat ctt cta gaa atg tgt cgt caa cga ggc 189
Pro Val Cys Tyr Ile Asn Leu Leu Glu Met Cys Arg Gln Arg Gly
50 55 60
tgatcgtcca ggaccctctg aaccacgacg t 220
<210> 99
<211> 63
<212> PRT
<213> Conus sulcatus
<400> 99
Met Phe Thr Val Phe Leu Leu Val Leu Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Asn Ser Asp Arg Ala Leu Gly Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
Ser Asp Lys Ile Leu Ser Asn Leu Arg Arg Gl.y Gly Cys Cys Phe His
35 40 45
Pro Val Cys Tyr Ile Asn Leu Leu Glu Met Cys Arg Gln Arg Gly
50 `_S5 60
<210> 100
<211> 208
<212> DNA
<213> Conus consors
<220>
<221> CDS
CA 02361534 2002-02-22
48
<222> (1)..(177)
<400> 100
atg ttc acc gtg ttt ctg ttg gtt gtc ttg aca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser
1 5 10 15
ttc cct tca gat agt gca tct gat gtc agg gat gac gaa gcc aaa gac 96
Phe Pro Ser Asp Ser Ala Ser Asp Val Arg Asp Asp Glu Ala Lys Asp
20 25 30
gaa agg tct gac atg tac aaa tcg aaa cgg aat gga cgc tgt tgc cat 144
Glu Arg Ser Asp Met Tyr Lys Ser Lys Arg Asn Gly Arg Cys Cys His
35 40 45
cct gcc tgt ggc aaa cac ttt agt tgt gga cgc tgatgctcca ggaccctctg 197
Pro Ala Cys Gly Lys His Phe Ser Cys Gly Arg
50 55
aaccacgacg t 208
<210> 101
<211> 59
<212> PRT
<213> Conus consors
<400> 101
Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser
1 5 10 15
Phe Pro Ser Asp Ser Ala Ser Asp Val Arg Asp Asp Glu Ala Lys Asp
20 25 30
Glu Arg Ser Asp Met Tyr Lys Ser Lys Arg Asn Gly Arg Cys Cys His
35 40 45
Pro Ala Cys Gly Lys His Phe Ser Cys Gly Arg
50 55
<210> 102
<211> 219
<212> DNA
<213> Conus stercusmuscarum
<220>
<221> CDS
<222> (1) .. (189)
<400> 102
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
CA 02361534 2002-02-22
49
tcc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac gag 96
Ser Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Glu
20 25 30
aaa gcg tct gac gtg atc gcg ctg gcc ctc aag gga tgc tgt tcc aac 144
Lys Ala Ser Asp Val Ile Ala Leu Ala Leu Lys Gly Cys Cys Ser Asn
35 40 45
cct gtc tgt cac ctg gag cat tca aac atg tgt ggt aga aga cgc 189
Pro Val Cys His Leu Glu His Ser Asn Met Cys Gly Arg Arg Arg
50 55 60
tgatgctcca ggaccctctg aaccacgacg 219
<210> 103
<211> 63
<212> PRT
<213> Conus stercusmuscarum
<400> 103
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Ser Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Glu
20 25 30
Lys Ala Ser Asp Val Ile Ala Leu Ala Leu Lys Gly Cys Cys Ser Asn
35 40 45
Pro Val Cys His Leu Glu His Ser Asn Met Cys Gly Arg Arg Arg
50 55 60
<210> 104
<211> 248
<212> DNA
<213> Conus betulinus
<220>
<221> CDS
<222> (1)..(180)
<400> 104
atg ttc tcc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Ser Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
tcc act tca ggt ggt gca tct ggt ggc agg aag get gca gcc aaa gcg 96
Ser Thr Ser Gly Gly Ala Ser Gly Gly Arg Lys Ala Ala Ala Lys Ala
20 25 30
tct aac cgg atc get ctg acc gtc agg agt gca aca tgc tgt aat tat 144
Ser Asn Arg Ile Ala Leu Thr Val Arg Ser Ala Thr Cys Cys Asn Tyr
35 40 45
CA 02361534 2002-02-22
cct ccc tgt tac gag act tat cca gaa agt tgt ctg taacgtgaat 190
Pro Pro Cys Tyr Glu Thr Tyr Pro Glu Ser Cys Leu
50 55 60
catccagagc tttgtggctg aagacactga tgctccagga ccctctgaac cacgacgt 248
<210> 105
<211> 60
<212> PRT
<213> Conus betulinus
<400> 105
Met Phe Ser Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Ser Thr Ser Gly Gly Ala Ser Gly Gly Arg Lys Ala Ala Ala Lys Ala
20 25 30
Ser Asn Arg Ile Ala Leu Thr Val Arg Ser Ala Thr Cys Cys Asn Tyr
35 40 45
Pro Pro Cys Tyr Glu Thr Tyr Pro Glu Ser Cys Leu
50 5 60
<210> 106
<211> 223
<212> DNA
<213> Conus betulinus
<220>
<221> CDS
<222> (1)..(183)
<400> 106
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtg gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca ggt cgt gca ttt cgt ggc agg aat cgc gca gcc gac gac 96
Phe Thr Ser Gly Arg Ala Phe Arg Gly Arg Asn Arg Ala Ala Asp Asp
20 25 30
aaa agg tct gac ctg gcc get ctg agc gtc agg gga gga tgc tgt tcc 144
Lys Arg Ser Asp Leu Ala Ala Leu Ser Val Arg Gly Gly Cys Cys Ser
35 40 45
cat cct gcc tgt gcg gtg aa.t cat cca gag ctt tgt ggc tgaagacgct 193
His Pro Ala Cys Ala Val Asn His Pro Glu Leu Cys Gly
50 55 60
gatgccccag gaccctctga accacgacgt 223
CA 02361534 2002-02-22
51
<210> 107
<211> 61
<212> PRT
<213> Conus betulinus
<400> 107
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Gly Arg Ala Phe Arg Gly Arg Asn Arg Ala Ala Asp Asp
20 25 30
Lys Arg Ser Asp Leu Ala Ala Leu Ser Val Arg Gly Gly Cys Cys Ser
35 40 45
His Pro Ala Cys Ala Val Asn His Pro Glu Leu Cys Gly
50 55 60
<210> 108
<211> 248
<212> DNA
<213> Conus betulinus
<220>
<221> CDS
<222> (1)..(180)
<400> 108
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca ggt cgt gca tct ggt ggc agg aat get gca gcc aaa gcg 96
Phe Thr Ser Gly Arg Ala Ser Gly Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
tct aac cgg atc get atg gcc atc agc agt gga gca tgc tgt gca tat 144
Ser Asn Arg Ile Ala Met Ala Ile Ser Ser Gly Ala Cys Cys Ala Tyr
35 40 45
cct ccc tgt ttc gag get tat cca gaa aga tgt ctg taacgtgaat 190
Pro Pro Cys Phe Glu Ala Tyr Pro Glu Arg Cys Leu
50 135 60
catccagacc tttgtggctg aagacgctga tgccccagga ccctctgaac cacgacgt 248
<210> 109
<211> 60
<212> PRT
<213> Conus betulinus
<400> 109
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
CA 02361534 2002-02-22
52
Phe Thr Ser Gly Arg Ala Ser Gly Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
Ser Asn Arg Ile Ala Met Ala Ile Ser Ser Gly Ala Cys Cys Ala Tyr
35 40 45
Pro Pro Cys Phe Glu Ala Tyr Pro Glu Arg Cys Leu
50 55 60
<210> 110
<211> 223
<212> DNA
<213> Conus betulinus
<220>
<221> CDS
<222> (1)..(192)
<400> 110
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca gat cgt gca ttt; cgt ggc agg aat tcc gca gcc aac gac 96
Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn Ser Ala Ala Asn Asp
20 25 30
aaa agg tct gac ctg gcc gut ctg agc gtc agg aga gga tgc tgc tcc 144
Lys Arg Ser Asp Leu Ala Ala Leu Ser Val Arg Arg Gly Cys Cys Ser
35 40 45
cat ccc gcc tgt agc gtg aat cat cca gag ctt tgt ggt aga aga cgc 192
His Pro Ala Cys Ser Val Asn His Pro Glu Leu Cys Gly Arg Arg Arg
50 55 60
tgatgcccca ggaccctctg aaccacgacg t 223
<210> 111
<211> 64
<212> PRT
<213> Conus betulinus
<400> 111
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Asp Arg Ala Phe Arg Gly Arq Asn Ser Ala Ala Asn Asp
20 25 30
Lys Arg Ser Asp Leu Ala Ala Leu Ser Val Arg Arg Gly Cys Cys Ser
35 40 45
His Pro Ala Cys Ser Val Asn His Pro Glu Leu Cys Gly Arg Arg Arg
50 455 60
CA 02361534 2002-02-22
53
<210> 112
<211> 248
<212> DNA
<213> Conus betulinus
<220>
<221> CDS
<222> (1)..(180)
<400> 112
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tea ggt cgt gca tet ggt ggc agg aat get gca gee aaa gcg 96
Phe Thr Ser Gly Arg Ala Ser Gly Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
tct aac egg ate get ctg ate gtc agg aat gca gaa tgc tgt tat tat 144
Ser Asn Arg Ile Ala Leu Ile Val Arg Asn Ala Glu Cys Cys Tyr Tyr
35 40 45
ect ecc tgt tae gag get tat cca gaa att tgt ctg taacgtgaat 190
Pro Pro Cys Tyr Glu Ala Tyr Pro Glu Ile Cys Leu
50 55 60
catccagacc tttgtggctg aagaccctga tgctccagga ccctctgaac cacgacgt 248
<210> 113
<211> 60
<212> PRT
<213> Conus betulinus
<400> 113
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Gly Arg Ala Ser Gly Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
Ser Asn Arg Ile Ala Leu Ile Val Arg Asn Ala Glu Cys Cys Tyr Tyr
35 40 45
Pro Pro Cys Tyr Glu Ala Tyr Pro Glu Ile Cys Leu
50 55 60
<210> 114
<211> 207
<212> DNA
<213> Conus pennaceus
CA 02361534 2002-02-22
54
<220>
<221> CDS
<222> (1)..(168)
<400> 114
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc att tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Ile Ser
1 5 10 15
ttc act tca gat cgt gca tct gat ggc ggg aat gcc gca gcg tct gac 96
Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Ala Ala Ala Ser Asp
20 25 30
ctg atc get ctg acc atc aag gga tgc tgt tct cat cct ccc tgt gcc 144
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Ala
35 40 45
atg aat aat cca gac tat tgt ggt tgacgacgct gatgctccag gaccctctga 198
Met Asn Asn Pro Asp Tyr Cys Gly
50 55
accacgacg 207
<210> 115
<211> 56
<212> PRT
<213> Conus pennaceus
<400> 115
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Ile Ser
1 5 10 15
Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Ala Ala Ala Ser Asp
20 25 30
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Ala
35 40 45
Met Asn Asn Pro Asp Tyr Cys Gly
50 55
<210> 116
<211> 207
<212> DNA
<213> Conus pennaceus
<220>
<221> CDS
<222> (1)..(168)
<400> 116
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu A:La Thr Thr Val Val Ser
1 5 10 15
CA 02361534 2002-02-22
ttc act tca gat cgt gca t.ct gat ggc ggg aat gcc gca atg tct gac 96
Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Ala Ala Met Ser Asp
20 25 30
ctg atc get ctg acc atc aag gga tgc tgt tct cat cct ccc tgt ttc 144
Leu Ile Ala Leu Thr Ile L's Gly Cys Cys Ser His Pro Pro Cys Phe
35 40 45
ctg aat aat cca gac tat tgt ggt tgacgacgct gatgctccag gaccctctga 198
Leu Asn Asn Pro Asp Tyr Cys Gly
50 55
accacgacg 207
<210> 117
<211> 56
<212> PRT
<213> Conus pennaceus
<400> 117
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Asp Arg Ala Sex- Asp Gly Gly Asn Ala Ala Met Ser Asp
20 25 30
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Phe
35 40 45
Leu Asn Asn Pro Asp Tyr Cys Gly
50 55
<210> 118
<211> 210
<212> DNA
<213> Conus stercusmuscarum
<220>
<221> CDS
<222> (1)..(171)
<400> 118
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Lei..i Ala Thr Thr Val Val Ser
1 5 10 15
ttc cct tca gat cgt gaa tct gat ggc gcg aat gac gaa gcc cgc acc 96
Phe Pro Ser Asp Arg Glu Ser Asp Gly Ala Asn Asp Glu Ala Arg Thr
20 25 30
gac gag cct gag gag cac gga ccg gac agg aat gga tgc tgt agg aat 144
Asp Glu Pro Glu Glu His Gly Pro Asp Arg Asn Gly Cys Cys Arg Asn
35 40 45
CA 02361534 2002-02-22
56
cct gcc tgt gag agc cac aga tgt ggt tgacgacgct gatgctccag 191
Pro Ala Cys Glu Ser His Arg Cys Gly
50 55
gaccctctga accacgacg 210
<210> 119
<211> 57
<212> PRT
<213> Conus stercusmuscarum
<400> 119
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Pro Ser Asp Arg Glu Ser Asp Gly Ala Asn Asp Glu Ala Arg Thr
20 25 30
Asp Glu Pro Glu Glu His Gly Pro Asp Arg Asn Gly Cys Cys Arg Asn
35 40 45
Pro Ala Cys Glu Ser His Arg Cys Gly
50 55
<210> 120
<211> 210
<212> DNA
<213> Conus circumcisus
<220>
<221> CDS
<222> (1) .. (180)
<400> 120
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc cct tca gat cgt gca t(-,,t. gat ggc agg aat gcc gca gcc agc gac 96
Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Ser Asp
20 25 30
aga gcg tct gac gcg gcc cac cag gga tgc tgt tcc aac cct gtc tgt 144
Arg Ala Ser Asp Ala Ala His Gln Gly Cys Cys Ser Asn Pro Val Cys
35 40 45
cac gtg gaa cat cca gaa ctt tgt cgt aga aga cgc tgatgctcca 190
His Val Glu His Pro Glu Leu Cys Arg Arg Arg Arg
50 55 60
CA 02361534 2002-02-22
57
ggaccctctg aaccacgacg 210
<210> 121
<211> 60
<212> PRT
<213> Conus circumcisus
<400> 121
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Ser Asp
20 25 30
Arg Ala Ser Asp Ala Ala His Gln Gly Cys Cys Ser Asn Pro Val Cys
35 40 45
His Val Glu His Pro Glu Leu Cys Arg Arg Arg Arg
50 55 60
<210> 122
<211> 213
<212> DNA
<213> Conus circumcisus
<220>
<221> CDS
<222> (1)..(174)
<400> 122
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc cct tca aat cgt gaa tot gat ggc gcg aat gcc gaa gtc cgc acc 96
Phe Pro Ser Asn Arg Glu Ser Asp Gly Ala Asn Ala Glu Val Arg Thr
20 25 30
gac gag cct gag gag cac gac gaa ctg ggc ggg aat gga tgc tgt ggg 144
Asp Glu Pro Glu Glu His Asp Glu Leu Gly Gly Asn Gly Cys Cys Gly
35 40 45
aat cct gac tgt acg agc cac agt tgt gat tgacgacgct gatgctccag 194
Asn Pro Asp Cys Thr Ser H:is Ser Cys Asp
50 55
gaccctctga accacgacg 213
<210> 123
<211> 58
<212> PRT
<213> Conus circumcisus
CA 02361534 2002-02-22
58
<400> 123
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Pro Ser Asn Arg Glu Ser Asp Gly Ala Asn Ala Glu Val Arg Thr
20 25 30
Asp Glu Pro Glu Glu His Asp Glu Leu Gly Gly Asn Gly Cys Cys Gly
35 40 45
Asn Pro Asp Cys Thr Ser His Ser Cys Asp
50 55
<210> 124
<211> 207
<212> DNA
<213> Conus episcopatus
<220>
<221> CDS
<222> (1)..(168)
<400> 124
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca. acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca gat cgt gca tct gat agc agg aag gac gca gcg tct ggc 96
Phe Thr Ser Asp Arg Ala Ser Asp Ser Arg Lys Asp Ala Ala Ser Gly
20 25 30
ctg atc get ctg acc atc aag gga tgc tgt tct gat cct cgc tgt aac 144
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser Asp Pro Arg Cys Asn
35 40 45
atg aat aat cca gac tat tgt: ggt tgacgacgct gatgctccag gaccctctga 198
Met Asn Asn Pro Asp Tyr Cys Gly
50 55
accacgacg 207
<210> 125
<211> 56
<212> PRT
<213> Conus episcopatus
<400> 125
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Asp Arg Ala Ser Asp Ser Arg Lys Asp Ala Ala Ser Gly
20 25 30
CA 02361534 2002-02-22
59
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser Asp Pro Arg Cys Asn
35 40 45
Met Asn Asn Pro Asp Tyr Cys Gly
50 55
<210> 126
<211> 213
<212> DNA
<213> Conus sponsalis
<220>
<221> CDS
<222> (1)..(174)
<400> 126
atg tcc acc gtg ttt ctg ttg gtt gtc ctc gca acc acc gtc gtt tcc 48
Met Ser Thr Val Phe Leu Lieu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act gta gat cgt gca tct gat ggc agg gat gtc gca atc gac gac 96
Phe Thr Val Asp Arg Ala Sear Asp Gly Arg Asp Val Ala Ile Asp Asp
20 25 30
aga ttg gtg tct ctc cct cag atc gcc cat get gac tgt tgt tcc gat 144
Arg Leu Val Ser Leu Pro Gin Ile Ala His Ala Asp Cys Cys Ser Asp
35 40 45
cct gcc tgc aag cag acg ccc ggt tgt cgt taaagacgct gctgctccag 194
Pro Ala Cys Lys Gln Thr Pro Gly Cys Arg
50 55
gaccctctga accacgacg 213
<210> 127
<211> 58
<212> PRT
<213> Conus sponsalis
<400> 127
Met Ser Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Val Asp Arg Ala Ser Asp Gly Arg Asp Val Ala Ile Asp Asp
20 25 30
Arg Leu Val Ser Leu Pro Gin Ile Ala His Ala Asp Cys Cys Ser Asp
35 40 45
Pro Ala Cys Lys Gln Thr Pro Gly Cys Arg
50 55
<210> 128
CA 02361534 2002-02-22
<211> 221
<212> DNA
<213> Conus sponsalis
<220>
<221> CDS
<222> (1)..(168)
<400> 128
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc get tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Ala Ser
1 5 10 15
ttc att atc gat gat cca tct: gat ggc agg aat att gca gtc gac gac 96
Phe Ile Ile Asp Asp Pro Ser Asp Gly Arg Asn Ile Ala Val Asp Asp
20 25 30
aga ggg ctt ttc tct acg ctc ttc cat get gat tgc tgt gaa aat cct 144
Arg Gly Leu Phe Ser Thr Leu Phe His Ala Asp Cys Cys Glu Asn Pro
35 40 45
gcc tgt aga cac acg cag ggt tgt tgatctttgt tcttcaaaga cactgctggc 198
Ala Cys Arg His Thr Gln Gly Cys
50 55
ccaggaccct ctgaaccacg acg 221
<210> 129
<211> 56
<212> PRT
<213> Conus sponsalis
<400> 129
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Ala Ser
1 5 10 15
Phe Ile Ile Asp Asp Pro Ser Asp Gly Arg Asn Ile Ala Val Asp Asp
20 25 30
Arg Gly Leu Phe Ser Thr Leu Phe His Ala Asp Cys Cys Glu Asn Pro
35 40 45
Ala Cys Arg His Thr Gln Gly Cys
so 55
<210> 130
<211> 220
<212> DNA
<213> Conus dalii
<220>
<221> CDS
<222> (1)..(180)
CA 02361534 2002-02-22
61
<400> 130
atg ttc acc gtg ttt ctg tt:g gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Le:u Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca gat cgt gca tt:t cgt ggc agg aat gcc gca gcc aaa gag 96
Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys Glu
20 25 30
tct ggc ctg gtc ggt ctg acc gac aag acg cga gga tgc tgt tct cat 144
Ser Gly Leu Val Gly Leu Thr Asp Lys Thr Arg Gly Cys Cys Ser His
35 40 45
cct gcc tgt aac gta gat cat cca gaa att tgt ggt tgaagacgct 190
Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Gly
50 55 60
gatgctccag gaccctctga accacgacgt 220
<210> 131
<211> 60
<212> PRT
<213> Conus dalli
<400> 131
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys Glu
20 25 30
Ser Gly Leu Val Gly Leu Thr Asp Lys Thr Arg Gly Cys Cys Ser His
35 40 45
Pro Ala Cys Asn Val Asp His Pro Glu Ile Cys Gly
50 55 60
<210> 132
<211> 208
<212> DNA
<213> Conus dalli
<220>
<221> CDS
<222> (1)..(177)
<400> 132
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca gat ggt gca tct gat gac agg aaa gcc get gcg tct gac 96
Phe Thr Ser Asp Gly Ala Ser Asp Asp Arg Lys Ala Ala Ala Ser Asp
20 25 30
CA 02361534 2002-02-22
62
ctg ate act ctg acc atc aag gga tgc tgt tct cgt cct ccc tgt atc 144
Leu Ile Thr Leu Thr Ile Lys Gly Cys Cys Ser Arg Pro Pro Cys Ile
35 40 45
gcg aat aat cca gac ttg tgt ggt cga cga cgc tgatgctcca ggaccctctg 197
Ala Asn Asn Pro Asp Leu Cys Gly Arg Arg Arg
50 55
aaccacgacg t 208
<210> 133
<211> 59
<212> PRT
<213> Conus dalli
<400> 133
Met Phe Thr Val Phe Leu Levu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Asp Gly Ala Ser Asp Asp Arg Lys Ala Ala Ala Ser Asp
20 25 30
Leu Ile Thr Leu Thr Ile Lys Gly Cys Cys Ser Arg Pro Pro Cys Ile
35 40 45
Ala Asn Asn Pro Asp Leu Cys Gly Arg Arg Arg
50 55
<210> 134
<211> 223
<212> DNA
<213> Conus dalli
<220>
<221> CDS
<222> (1)..(192)
<400> 134
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
tee act tea ggt cgt cgt gca ttt cat ggc agg aat gcc gca gcc aaa 96
Ser Thr Ser Gly Arg Arg Ala Phe His Gly Arg Asn Ala Ala Ala Lys
20 25 30
gcg tct gga ctg gtc ggt ctg act gac agg aga cca caa tgc tgt agt 144
Ala Ser Gly Leu Val Gly Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser
35 40 45
gat cct cgc tgt aac gta ggt cat cca gaa ctt tgt ggt gga aga cgc 192
Asp Pro Arg Cys Asn Val Gly His Pro Glu Leu Cys Gly Gly Arg Arg
50 55 60
CA 02361534 2002-02-22
63
tgatgctcca ggaccctctg aaccacaacg t 223
<210> 135
<211> 64
<212> PRT
<213> Conus dalli
<400> 135
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Ser Thr Ser Gly Arg Arg Ala Phe His Gly Arg Asn Ala Ala Ala Lys
20 25 30
Ala Ser Gly Leu Val Gly Leu Thr Asp Arg Arg Pro Gln Cys Cys Ser
35 40 45
Asp Pro Arg Cys Asn Val Gly His Pro Glu Leu Cys Gly Gly Arg Arg
50 55 60
<210> 136
<211> 220
<212> DNA
<213> Conus dalli
<220>
<221> CDS
<222> (1)..(189)
<400> 136
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
tcc act tca ggt cgt gca ttt cat ggc agg aat gcc gca gcc aaa gcg 96
Ser Thr Ser Gly Arg Ala Phe His Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
tct ggc ctg gtc ggt ctg acc gac aag agg caa gta tgc tgt agt gat 144
Ser Gly Leu Val Gly Leu Thr Asp Lys Arg Gln Val Cys Cys Ser Asp
35 40 45
cct cgc tgt aac gta ggt cat cca gaa att tgt ggt gga aga cgc 189
Pro Arg Cys Asn Val Gly His Pro Glu Ile Cys Gly Gly Arg Arg
50 55 60
tgatgctcca ggaccctctg aaccacgacg t 220
<210> 137
<211> 63
CA 02361534 2002-02-22
64
<212> PRT
<213> Conus dalli
<400> 137
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Ser Thr Ser Gly Arg Ala Phe His Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
Ser Gly Leu Val Gly Leu Thr Asp Lys Arg Gln Val Cys Cys Ser Asp
35 40 45
Pro Arg Cys Asn Val Gly His Pro Glu Ile Cys Gly Gly Arg Arg
50 13 5 60
<210> 138
<211> 208
<212> DNA
<213> Conus achatinus
<220>
<221> CDS
<222> (1)..(180)
<400> 138
atg ttc acc gtg ttt ctg ttg gtt gtc ttg aca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser
1 5 10 15
ttc cct tca gat agt gca tct ggt ggc agg gat gac gag gcc aaa gac 96
Phe Pro Ser Asp Ser Ala Ser Gly Gly Arg Asp Asp Glu Ala Lys Asp
20 25 30
gaa agg tct gac atg tac gaa ttg aaa cgg aat gga cgc tgt tgc cat 144
Glu Arg Ser Asp Met Tyr Glu Leu Lys Arg Asn Gly Arg Cys Cys His
35 40 45
cct gcc tgt ggt ggc aaa tac gtt aaa tgt gga cgc tgatgctcca 190
Pro Ala Cys Gly Gly Lys Tyr Val Lys Cys Gly Arg
50 55 60
ggaccctctc gaaccacg 208
<210> 139
<211> 60
<212> PRT
<213> Conus achatinus
<400> 139
Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser
1 5 10 15
CA 02361534 2002-02-22
Phe Pro Ser Asp Ser Ala Ser Gly Gly Arg Asp Asp Glu Ala Lys Asp
20 25 30
Glu Arg Ser Asp Met Tyr Glu Leu Lys Arg Asn Gly Arg Cys Cys His
35 40 45
Pro Ala Cys Gly Gly Lys Tyr Val Lys Cys Gly Arg
50 55 60
<210> 140
<211> 211
<212> DNA
<213> Conus bullatus
<220>
<221> CDS
<222> (1)..(174)
<400> 140
atg ttc acc gtg ttt ctg tt:g gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc tct aca gat gat gaa tct gat ggc tcg aat gaa gaa ccc agc gcc 96
Phe Ser Thr Asp Asp Glu Seer Asp Gly Ser Asn Glu Glu Pro Ser Ala
20 25 30
gac cag act gcc agg tcc tca atg aac agg gcg cct gga tgc tgt aac 144
Asp Gln Thr Ala Arg Ser Ser Met Asn Arg Ala Pro Gly Cys Cys Asn
35 40 45
aat cct gcc tgt gtg aag cac aga tgt gga tgacgctgat gctccaggac 194
Asn Pro Ala Cys Val Lys His Arg Cys Gly
50 55
cctctgaacc acgacgt 211
<210> 141
<211> 58
<212> PRT
<213> Conus bullatus
<400> 141
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Ser Thr Asp Asp Glu Ser Asp Gly Ser Asn Glu Glu Pro Ser Ala
20 25 30
Asp Gln Thr Ala Arg Ser Ser Met Asn Arg Ala Pro Gly Cys Cys Asn
35 40 45
Asn Pro Ala Cys Val Lys His Arg Cys Gly
50 55
CA 02361534 2002-02-22
66
<210> 142
<211> 214
<212> DNA
<213> Conus bullatus
<220>
<221> CDS
<222> (1)..(177)
<400> 142
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc tct aca gat gat gaa tct gat ggc tcg aat gaa gaa ccc agc gcc 96
Phe Ser Thr Asp Asp Glu Ser Asp Gly Ser Asn Glu Glu Pro Ser Ala
20 25 30
gac cag get gcc agg tcc gca atg aac agg ccg cct gga tgc tgt aac 144
Asp Gln Ala Ala Arg Ser Ala Met Asn Arg Pro Pro Gly Cys Cys Asn
35 40 45
aat cct gcc tgt gtg aag cac aga tgt ggt gga tgacgctgat gctccaggac 197
Asn Pro Ala Cys Val Lys His Arg Cys Gly Gly
50 55
cctctgaacc acgacgt 214
<210> 143
<211> 59
<212> PRT
<213> Conus bullatus
<400> 143
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Ser Thr Asp Asp Glu Ser Asp Gly Ser Asn Glu Glu Pro Ser Ala
20 25 30
Asp Gln Ala Ala Arg Ser Ala Met Asn Arg Pro Pro Gly Cys Cys Asn
35 40 45
Asn Pro Ala Cys Val Lys His Arg Cys Gly Gly
50 55
<210> 144
<211> 208
<212> DNA
<213> Conus bullatus
CA 02361534 2002-02-22
67
<220>
<221> CDS
<222> (1)..(177)
<400> 144
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc cct tca gat cgt gac tct gat ggc gcg gat gcc gaa gcc agt gac 96
Phe Pro Ser Asp Arg Asp Ser Asp Gly Ala Asp Ala Glu Ala Ser Asp
20 25 30
gag cct gtt gag ttc gaa agg gac gag aat gga tgc tgt tgg aat cct 144
Glu Pro Val Glu Phe Glu Arg Asp Glu Asn Gly Cys Cys Trp Asn Pro
35 40 45
tcc tgt ccg agg ccc aga tgt aca gga cga cgc taatgctcca ggaccctctg 197
Ser Cys Pro Arg Pro Arg Cys Thr Gly Arg Arg
50 aaccacgacg t 208
<210> 145
<211> 59
<212> PRT
<213> Conus bullatus
<400> 145
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Pro Ser Asp Arg Asp Ser Asp Gly Ala Asp Ala Glu Ala Ser Asp
20 25 30
Glu Pro Val Glu Phe Glu Arg Asp Glu Asn Gly Cys Cys Trp Asn Pro
35 40 45
Ser Cys Pro Arg Pro Arg Cys Thr Gly Arg Arg
50 55
<210> 146
<211> 211
<212> DNA
<213> Conus bullatus
<220>
<221> CDS
<222> (1)..(180)
<400> 146
atg ttc acc gtg ttt ctg tt:g gtt gtc ttg aca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser
1 5 11) 15
CA 02361534 2002-02-22
68
ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac gac 96
Phe Pro Ser Asp Arg Ala Ser. Asp Gly Arg Asn Ala Ala Ala Asn Asp
20 25 30
aaa gcg tct gac gtg gtc acg ctg gtc ctc aag gga tgc tgt tcc acc 144
Lys Ala Ser Asp Val Val Thr Leu Val Leu Lys Gly Cys Cys Ser Thr
35 40 45
cct ccc tgt get gtg ctg tat tgt ggt aga aga cgc tgatgctcca 190
Pro Pro Cys Ala Val Leu Tyr Cys Gly Arg Arg Arg
50 55 60
ggaccctctg aaccacgacg t 211
<210> 147
<211> 60
<212> PRT
<213> Conus bullatus
<400> 147
Met Phe Thr Val Phe Leu Leu Val Val Leu Thr Thr Thr Val Val Ser
1 5 10 15
Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp
20 25 30
Lys Ala Ser Asp Val Val Thr Leu Val Leu Lys Gly Cys Cys Ser Thr
35 40 45
Pro Pro Cys Ala Val Leu Tyr Cys Gly Arg Arg Arg
50 55 60
<210> 148
<211> 212
<212> DNA
<213> Conus distans
<220>
<221> CDS
<222> (1)..(171)
<400> 148
atg ttc acc gtg ttt ctg ttg gtt gtc ttc gca tcc tct gtc acc tta 48
Met Phe Thr Val Phe Leu Leu Val Val Phe Ala Ser Ser Val Thr Leu
1 5 10 15
gat cgt gca tct tat ggc agg tat gcc tca ccc gtc gac aga gcg tct 96
Asp Arg Ala Ser Tyr Gly Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser
20 25 30
gcc ctg atc get cag gcc atc ctt cga gat tgc tgc tcc aat cct cct 144
Ala Leu Ile Ala Gln Ala Isle Leu Arg Asp Cys Cys Ser Asn Pro Pro
35 40 45
CA 02361534 2002-02-22
69
tgt gcc cat aat aat cca gac tgt cgt taaagacgct gcttgctcca 191
Cys Ala His Asn Asn Pro Asp Cys Arg
50 55
ggaccctctg aaccacgacg t 212
<210> 149
<211> 57
<212> PRT
<213> Conus distans
<400> 149
Met Phe Thr Val Phe Leu Levu Val Val Phe Ala Ser Ser Val Thr Leu
1 5 10 15
Asp Arg Ala Ser Tyr Gly Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser
20 25 30
Ala Leu Ile Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro
35 40 45
Cys Ala His Asn Asn Pro Asp Cys Arg
50 55
<210> 150
<211> 63
<212> DNA
<213> Conus textile
<220>
<221> CDS
<222> (1)..(60)
<400> 150
gga tgc tgt tct aat cct ccc tgt atc gcg aag aat cca cac atg tgt 48
Gly Cys Cys Ser Asn Pro Pro Cys Ile Ala Lys Asn Pro His Met Cys
1 5 10 15
ggt gga aga cgc tga 63
Gly Gly Arg Arg
<210> 151
<211> 20
<212> PRT
<213> Conus textile
<400> 151
Gly Cys Cys Ser Asn Pro Pro Cys Ile Ala Lys Asn Pro His Met Cys
1 5 1.0 15
Gly Gly Arg Arg
CA 02361534 2002-02-22
<210> 152
<211> 220
<212> DNA
<213> Conus consors
<220>
<221> CDS
<222> (1)..(189)
<400> 152
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc cct tca gat cgt gca tct gat ggc agg aat gcc gca gcc aac gac 96
Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp
20 25 30
aaa gcg tct gac gtg atc acg ctg gcc ctc aag gga tgc tgt tcc aac 144
Lys Ala Ser Asp Val Ile Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn
35 40 45
cct gtc tgt cac ttg gag cat tca aac ctt tgt ggt aga aga cgc 189
Pro Val Cys His Leu Glu His Ser Asn Leu Cys Gly Arg Arg Arg
50 55 60
tgatgctcca ggaccctctg aaccacgacg t 220
<210> 153
<211> 63
<212> PRT
<213> Conus consors
<400> 153
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Pro Ser Asp Arg Ala Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp
20 25 30
Lys Ala Ser Asp Val Ile Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn
35 40 45
Pro Val Cys His Leu Glu His Ser Asn Leu Cys Gly Arg Arg Arg
50 55 60
<210> 154
CA 02361534 2002-02-22
71
<211> 15
<212> PRT
<213> Conus musicus
<220>
<221> PEPTIDE
<222> (4)..(12)
<223> Xaa at residues 4, 11 and 12 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, 0-sulpho-Tyr,
0-phospho-Tyr or nitro-Tyr. Xaa at residue 6 is
Pro or hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (9)..(15)
<223> Xaa at residues 9, 10 and 15 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa at
residue 14 is Trp (D or L) or halo-Trp.
<400> 154
Gly Cys Cys Xaa Asn Xaa Val Cys Xaa Xaa Xaa Xaa Cys Xaa Xaa
1 5 10 15
<210> 155
<211> 16
<212> PRT
<213> Conus purpurascens
<220>
<221> PEPTIDE
<222> (1)..(3)
<223> Xaa at residue 1 is Gln or pyro-Glu; Xaa at
residue 2 is Glu or gamma-carboxy-Glu; Xaa at
residues 3 and 9 is Pro or hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (13)
<223> Xaa at residue 13 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyi-Lys.
<400> 155
Xaa Xaa Xaa Gly Cys Cys Arg His Xaa Ala Cys Gly Xaa Asn Arg Cys
1 5 10 15
<210> 156
<211> 13
<212> PRT
<213> Conus musicus
<220>
<221> PEPTIDE
<222> (5)..(11)
<223> Xaa at residues 5 and 11 is Pro or hydroxy-Pro.
CA 02361534 2002-02-22
72
<400> 156
Cys Cys Ala Asp Xaa Asp Cys Arg Phe Arg Xaa Gly Cys
1 5 10
<210> 157
<211> 17
<212> PRT
<213> Conus musicus
<220>
<221> PEPTIDE
<222> (4)..(13)
<223> Xaa at residues 4 and 13 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O--sulpho-Tyr,
0-phospho-Tyr or nitro-Tyr; Xaa at residues 6 and
is Pro or hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (9) .. (17)
<223> Xaa at residues 9 and 16 is Trp (D or L) or
halo-Trp; Xaa at residues 11 and 17 is Lys,
N-methyl-Lys, N,N-dimethyl-Lys or
N,N,N-trimethyl-Lys.
<400> 157
Gly Cys Cys Xaa Asn Xaa Ser Cys Xaa Xaa Xaa Thr Xaa Cys Ser Xaa
1 5 10 15
Xaa
<210> 158
<211> 13
<212> PRT
<213> Conus musicus
<220>
<221> PEPTIDE
<222> (5)..(8)
<223> Xaa at residue 5 is Pro or hydroxy-Pro; Xaa at
residue 8 is Lys, N-methyl-Lys, N,N-dimethyl-Lys
or N,N,N-trimethy:L-Lys.
<220>
<221> PEPTIDE
<222> (9)..(11)
<223> Xaa at residue 9 is Glu or gamma-carboxy-Glu; Xaa
at residue 11 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-su.lpho-Tyr, 0-phospho-Tyr or
nitro-Tyr.
<400> 158
CA 02361534 2002-02-22
73
Cys Cys Ser Asn Xaa Thr Cys Xaa Xaa Thr Xaa Gly Cys
1 5 10
<210> 159
<211> 13
<212> PRT
<213> Conus musicus
<220>
<221> PEPTIDE
<222> (5)..(11)
<223> Xaa at residues 5 and 11 is Pro or hydroxy-Pro;
Xaa at residue 8 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<400> 159
Cys Cys Ala Asn Xaa Ile Cys Xaa Asn Thr Xaa Gly Cys
1 5 10
<210> 160
<211> 13
<212> PRT
<213> Conus musicus
<220>
<221> PEPTIDE
<222> (5) .. (8)
<223> Xaa at residue 5 is Pro or hydroxy-Pro; Xaa at
residue 8 is Lys, N'-methyl-Lys, N,N-dimethyl-Lys
or N,N,N-trimethyl.-]Lys.
<220>
<221> PEPTIDE
<222> (9) .. (11)
<223> Xaa at residue 9 is Glu or gamma-carboxy-Glu; Xaa
at residue 11 is Tyr, mono-halo-Tyr, di-halo-Tyr,
O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr.
<400> 160
Cys Cys Asn Asn Xaa Thr Cys Xaa Xaa Thr Xaa Gly Cys
1 5 10
<210> 161
<211> 13
<212> PRT
<213> Conus musicus
<220>
<221> PEPTIDE
<222> (5) .. (8)
<223> Xaa at residue 5 is Pro or hydroxy-Pro; Xaa at
residue 8 is Lys, N-methyl-Lys, N,N-dimethyl-Lys
CA 02361534 2002-02-22
74
or N, N,N-trimethyl-Lys.
<220>
<221> PEPTIDE
<222> (9)..(11)
<223> Xaa at residue 9 is Glu or gamma-carboxy-Glu; Xaa
at residue 11 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-suipho-Tyr, 0-phospho-Tyr or
nitro-Tyr.
<400> 161
Cys Cys Ser Asn Xaa Val Cys Xaa Xaa Thr Xaa Gly Cys
1 5 10
<210> 162
<211> 17
<212> PRT
<213> Conus betulinus
<220>
<221> PEPTIDE
<222> (6)..(14)
<223> Xaa at residue 6 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, 0-phospho-Tyr or
nitro-Tyr; Xaa at residues 7, 8 and 1.4 is Pro or
hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (15)
<223> Xaa at residue 15 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<400> 162
Gly Gly Cys Cys Ser Xaa Xaa Xaa Cys Ile Ala Ser Asn Xaa Xaa Cys
1 5 10 15
Gly
<210> 163
<211> 15
<212> PRT
<213> Conus lividus
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
<400> 163
Gly Cys Cys Ser His Xaa Val Cys Ser Ala Met Ser Xaa Ile Cys
1 5 10 15
CA 02361534 2002-02-22
<210> 164
<211> 15
<212> PRT
<213> Conus musicus
<220>
<221> PEPTIDE
<222> (4)..(12)
<223> Xaa at residues 4 and 12 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa at
residue 6 is Pro or hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (7)..(14)
<223> Xaa at residues 7 and 14 is Tyr, mono-halo-Tyr,
di-halo-Tyr, O-suipho-Tyr, O-phospho-Tyr or
nitro-Tyr.
<400> 164
Gly Cys Cys Xaa Asn Xaa Xaa Cys Gly Ala Ser Xaa Thr Xaa Cys
1 5 10 15
<210> 165
<211> 15
<212> PRT
<213> Conus omaria
<220>
<221> PEPTIDE
<222> (5)..(13)
<223> Xaa at residue 5 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residues 6, 7 and 13 is Pro or
hydroxy-Pro.
<400> 165
Gly Cys Cys Ser Xaa Xaa Xaa Cys Phe Ala Thr Asn Xaa Asp Cys
1 5 1.0 15
<210> 166
<211> 17
<212> PRT
<213> Conus radiatus
<220>
<221> PEPTIDE
<222> (6) .. (14)
<223> Xaa at residue 6 is Tyr, nor-Tyr, mono-halo.-Tyr,
di-halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr or
nitro-Tyr; Xaa at residues 7, 8 and 14 is Pro or
hydroxy-Pro.
CA 02361534 2002-02-22
76
<400> 166
Gly Gly Cys Cys Ser Xaa Xaa Xaa Cys Ile Ala Asn Asn Xaa Leu Cys
1 5 1O 15
Ala
<210> 167
<211> 17
<212> PRT
<213> Conus radiatus
<220>
<221> PEPTIDE
<222> (6).. (14)
<223> Xaa at residue 6 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr; Xaa at residues 7, 8 and 14 is Pro or
hydroxy-Pro.
<400> 167
Gly Gly Cys Cys Ser Xaa Xaa Xaa Cys Ile Ala Asn Asn Xaa Phe Cys
1 5 10 15
Ala
<210> 168
<211> 16
<212> PRT
<213> Conus virgo
<220>
<221> PEPTIDE
<222> (6) .. (13)
<223> Xaa at residues 6, 7 and 13 is Pro or hydroxy-Pro.
<400> 168
Asp Cys Cys Ser Asn Xaa Xaa Cys Ser Gin Asn Asn Xaa Asp Cys Met
1 5 10 15
<210> 169
<211> 16
<212> PRT
<213> Conus virgo
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6, 7 and 13 is Pro or hydroxy-Pro.
<400> 169
CA 02361534 2002-02-22
77
Asp Cys Cys Ser Asn Xaa Xaa Cys Ala His Asn Asn Xaa Asp Cys Arg
1 5 10 15
<210> 170
<211> 20
<212> PRT
<213> Conus achatinus
<220>
<221> PEPTIDE
<222> (1)..(14)
<223> Xaa at residues 1, -1 and 14 is Glu or
gamma-carboxy-Glu; Xaa at residue 6 is Pro or
hydroxy-Pro.
<400> 170
Xaa Cys Cys Thr Asn Xaa Val Cys His Ala Xaa His Gln Xaa Leu Cys
1 5 10 15
Ala Arg Arg Arg
<210> 171
<211> 16
<212> PRT
<213> Conus achatinus
<220>
<221> PEPTIDE
<222> (6)..(10)
<223> Xaa at residue 6 is Pro or hydroxy-Pro; Xaa at
residue 10 is Glu or gamma-carboxy-Glu.
<400> 171
Gly Cys Cys Ser Asn Xaa Val Cys His Leu Xaa His Ser Asn Leu Cys
1 5 10 15
<210> 172
<211> 20
<212> PRT
<213> Conus achatinus
<220>
<221> PEPTIDE
<222> (1)..(14)
<223> Xaa at residues 1, 11 and 14 is Glu or
gamma-carboxy-Glu; Xaa at residue 6 is Pro or
hydroxy-Pro.
<400> 172
Xaa Cys Cys Thr Asn Xaa Val Cys His Val Xaa His Gln Xaa Leu Cys
1 5 LO 15
CA 02361534 2002-02-22
78
Ala Arg Arg Arg
<210> 173
<211> 17
<212> PRT
<213> Conus ammiralis
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Xaa at residue 1 is Gln or pyro-Glu; Xaa at
residues 2 and 15 is Glu or gamma-carboxy-Glu; Xaa
at residue 6 is Tyr, nor--Tyr, mono-.halo-Tyr,
di-halo-Tyr, O-suipho-Tyr..
<220>
<221> PEPTIDE
<222> (6) .. (14)
<223> Xaa at residue 6 is also 0-phopho-Tyr or nitro-Tyr;
Xaa at residues 7 and 14 is Pro or hydroxy-Pro.
<400> 173
Xaa Xaa Cys Cys Ser Xaa Xaa Ala Cys Asn Leu Asp His Xaa Xaa Leu
1 5 10 15
Cys
<210> 174
<211> 18
<212> PRT
<213> Conus ammiralis
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Xaa at residues 1,. 7 and 14 is Pro or hydroxy-Pro;
Xaa at residues 2 and 15 is G1u or
gamma-carboxy-Glu.
<400> 174
Xaa Xaa Cys Cys Ser Asp Xaa Arg Cys Asn Ser Thr His Xaa Xaa Leu
1 5 1.0 15
Cys Gly
<210> 175
<211> 21
<212> PRT
CA 02361534 2002-02-22
?9
<213> Conus arenatus
<220>
<221> PEPTIDE
<222> (7)..(12)
<223> Xaa at residues 7 and 8 is Pro or hydroxy-Pro; Xaa
at residue 10 is Trp (D or L) or halo-Trp; Xaa at
residues 11 and 12 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl--Lys.
<220>
<221> PEPTIDE
<222> (13) .. (19)
<223> Xaa at residue 13 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-su.pho-Tyr, 0-phospho-Tyr or
nitro-Tyr ; Xaa at residue 19 is Glu or
gamma-carboxy-Glu.
<400> 175
Leu Asn Cys Cys Met Ile Xaa Xaa Cys Xaa Xaa Xaa Xaa Gly Asp Arg
1 5 10 15
Cys Ser Xaa Val Arg
<210> 176
<211> 22
<212> PRT
<213> Conus arenatus
<220>
<221> PEPTIDE
<222> (9)..(20)
<223> Xaa at residue 9 is Pro or hydroxy-Pro; Xaa at
residues 12 and 20 is Glu or gamma-carboxy-Glu.
<220>
<221> PEPTIDE
<222> (14)
<223> Xaa at residue 14 is Tyr, nor-Tyr, mono-halo-Tyr, di-
halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr or nitro-Tyr.
<400> 176
Ala Phe Gly Cys Cys Asp Leu Ile Xaa Cys Leu Xaa Arg Xaa Gly Asn
1 5 10 15
Arg Cys Asn Xaa Val His
<210> 177
<211> 21
<212> PRT
<213> Conus arenatus
CA 02361534 2002-02-22
<220>
<221> PEPTIDE
<222> (8)..(16)
<223> Xaa at residue 8 is Pro or hydroxy-Pro; Xaa at
residue 10 is Trp (D or L) or halo-=Trp; Xaa at
residues 12 and 16 is Lys, N-methyl.-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<220>
<221> PEPTIDE
<222> (11)..(19)
<223> Xaa at residues 1.1 and 19 is Glu. or
gamma-carboxy-Glu; Xaa at residue 1:3 is Tyr,
mono-halo-Tyr, di-halo-Tyr, 0-sulpho-Tyr,
0-phospho-Tyr or nitro-Tyr.
<400> 177
Leu Gly Cys Cys Asn Val Thr Xaa Cys Xaa Xaa Xaa Xaa Gly Asp Xaa
1 5 10 15
Cys Asn Xaa Val Arg
<210> 178
<211> 20
<212> PRT
<213> Conus arenatus
<220>
<221> PEPTIDE
<222> (2)..(14)
<223> Xaa at residue 2 is Glu or gamma-carboxy-Glu; Xaa
at residues 7 and 14 is Pro or hydroxy-Pro.
<400> 178
Asp Xaa Cys Cys Ser Asn Xaa Ala Cys Arg Val Asn Asn Xaa His Val
1 5 10 15
Cys Arg Arg Arg
<210> 179
<211> 21
<212> PRT
<213> Conus arenatus
<220>
<221> PEPTIDE
<222> (7)..(12)
<223> Xaa at residue 7 is Pro or hydroxy-Pro; Xaa at
residue 10 is Trp (D or L) or halo-Trp; Xaa at
residue 12 is Glu or gamma-carboxy-Glu.
CA 02361534 2002-02-22
81
<220>
<221> PEPTIDE
<222> (13)..(19)
<223> Xaa at residue 13 is Tyr, nor-Tyr, mono-halo-Tyr,di-
halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr or nitro-Tyr;
Xaa at residues 14 and 19 is Lys, N-methyl-Lys, N,N-
dimethyl-Lys or N, N,N-trimethyl-Lys.
<400> 179
Leu Asn Cys Cys Ser Ile Xaa Gly Cys Xaa Asn Xaa Xaa Xaa Asp Arg
1 5 1.0 15
Cys Ser Xaa Val Arg
<210> 180
<211> 18
<212> PRT
<213> Conus aurisiacus
<220>
<221> PEPTIDE
<222> (7)..(14)
<223> Xaa at residues 7 and 14 is Pro or hydroxy-Pro;
Xaa at residue 10 is Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr.
<400> 180
Gly Gly Cys Cys Ser His Xaa Val Cys Xaa Phe Asn Asn Xaa Gln Met
1 5 10 15
Cys Arg
<210> 181
<211> 18
<212> PRT
<213> Conus aurisiacus
<220>
<221> PEPTIDE
<222> (7)..(14)
<223> Xaa at residues 7 and 14 is Pro or hydroxy-Pro.
<400> 181
Gly Gly Cys Cys Ser His Xaa Val Cys Asn Leu Asn Asn Xaa Gln Met
1 5 10 15
Cys Arg
CA 02361534 2002-02-22
82
<210> 182
<211> 17
<212> PRT
<213> Conus bandanus
<220>
<221> PEPTIDE
<222> (6)..(15)
<223> Xaa at residues 6 and 7 is Pro or hydroxy-Pro; Xaa
at residues 9 and 15 is Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, 0-phospho-Tyr or
nitro-Tyr.
<400> 182
Gly Cys Cys Ser His Xaa Xaa Cys Xaa Ala Asn Asn Gln Ala Xaa Cys
1 5 10 15
Asn
<210> 183
<211> 17
<212> PRT
<213> Conus betulinus
<220>
<221> PEPTIDE
<222> (7)..(15)
<223> Xaa at residues 7 and 14 is Pro and hydroxy-Pro;
Xaa at residue 15 is Glu or gamma-carboxy-Glu.
<400> 183
Gly Gly Cys Cys Ser His Xaa Ala Cys Ser Val Thr His Xaa Xaa Leu
1 5 10 15
Cys
<210> 184
<211> 18
<212> PRT
<213> Conus betulinus
<220>
<221> PEPTIDE
<222> (6)..(7)
<223> Xaa at residue 6 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, 0-phospho-Tyr or
nitro-Tyr; Xaa at residue 7 is Pro and
hydroxy-Pro.
<220>
<221> PEPTIDE
CA 02361534 2002-02-22
83
<222> (12)
<223> Xaa at residue 12 is Glu or gamma-carboxy-Glu.
<400> 184
Gly Gly Cys Cys Ser Xaa Xaa Ala Cys Ser Val Xaa His Gln Asp Leu
1 5 10 15
Cys Asp
<210> 185
<211> 25
<212> PRT
<213> Conus caracteristicas
<220>
<221> PEPTIDE
<222> (8)..(22)
<223> Xaa at residues 8 and 22 is Pro or hydroxy-Pro;
Xaa at residue 10 is Trp (D or L) or halo-Trp.
<220>
<221> PEPTIDE
<222> (13) .. (19)
<223> Xaa at residue 13 is Tyr, nor--Tyr, mono-halo-Tyr, di-
halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr or nitro-Tyr;
Xaa at residues 15, 16 and 19 is Glu or gamma-
carboxy-Glu.
<400> 185
Val Ser Cys Cys Val Val Arg Xaa Cys Xaa Ile Arg Xaa Gin Xaa Xaa
1 5 10 15
Cys Leu Xaa Ala Asp Xaa Arg Thr Leu
20 25
<210> 186
<211> 21
<212> PRT
<213> Conus caracteristicas
<220>
<221> PEPTIDE
<222> (1)..(19)
<223> Xaa at residue 1 is Gln or pyro-Glu; Xaa at
residue 7 is Pro or hydroxy-Pro; Xaa at residue 10
is Trp (D or L) or halo-Trp; Xaa at residues 11
and 19 is Glu or gamma-carboxy-Glu.
<220>
<221> PEPTIDE
<222> (12)..(16)
CA 02361534 2002-02-22
84
<223> Xaa at residues 12 and 16 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa at
residue 13 is Tyr, mono-halo-Tyr, d_i-halo-Tyr,
0-sulpho-Tyr, 0-phospho-Tyr or nitro-Tyr.
<400> 186
Xaa Asn Cys Cys Ser Ile Xaa Gly Cys Xaa Xaa Xaa Xaa Gly Asp Xaa
1 5 10 15
Cys Ser Xaa Val Arg
<210> 187
<211> 16
<212> PRT
<213> Conus catus
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 11 is Glu or gamma-carboxy-Glu.
<400> 187
Gly Cys Cys Ser Asn Xaa Val Cys His Leu Xaa His Xaa Asn Ala Cys
1 5 10 15
<210> 188
<211> 17
<212> PRT
<213> Conus catus
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 9 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr.
<400> 188
Gly Cys Cys Ser Asn Xaa Ile Cys Xaa Phe Asn Asn Xaa Arg Ile Cys
1 5 10 15
Arg
<210> 189
<211> 17
<212> PRT
<213> Conus episcopatus
<220>
CA 02361534 2002-02-22
<221> PEPTIDE
<222> (1)..(14)
<223> Xaa at residues 1 and 14 is Glu or
gamma-carboxy-Glu; Xaa at residues 6, 7 and 13 is
Pro or hydroxy-Pro; Xaa at residue 10 is Trp (D or
L) or halo-Trp.
<220>
<221> PEPTIDE
<222> (11)
<223> Xaa at residue 11 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl.-Lys.
<400> 189
Xaa Cys Cys Ser Gln Xaa Xaa Cys Arg Xaa Xaa His Xaa Xaa Leu Cys
1 5 10 15
Ser
<210> 190
<211> 16
<212> PRT
<213> Conus geographus
<220>
<221> PEPTIDE
<222> (6)
<223> Xaa at residue 6 is Pro or hydroxy-Pro.
<400> 190
Gly Cys Cys Ser His Xaa Ala Cys Ala Gly Asn Asn Gln His Ile Cys
1 5 10 15
<210> 191
<211> 18
<212> PRT
<213> Conus geographus
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
<400> 191
Gly Cys Cys Ala Val Xaa Seer Cys Arg Leu Arg Asn Xaa Asp Leu Cys
1 5 10 15
Gly Gly
<210> 192
CA 02361534 2002-02-22
86
<211> 16
<212> PRT
<213> Conus imperialis
<220>
<221> NP BIND
<222> (6)..(13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
<400> 192
Gly Cys Cys Ser His Xaa Ala Cys Asn Val Asn Asn Xaa His Ile Cys
1 5 10 15
<210> 193
<211> 20
<212> PRT
<213> Conus lividus
<220>
<221> PEPTIDE
<222> (2)..(10)
<223> Xaa at residues 2, 7, 9 and 10 is Pro or
hydroxy-Pro; Xaa at residues 3 and 4 is Glu or
gamma-carboxy-Glu.
<400> 193
Thr Xaa Xaa Xaa Cys Cys Xaa Asn Xaa Xaa Cys Phe Ala Thr Asn Ser
1 5 10 15
Asp Ile Cys Gly
<210> 194
<211> 17
<212> PRT
<213> Conus lividus
<220>
<221> PEPTIDE
<222> (7)..(12)
<223> Xaa at residue 7 is Pro or hydroxy-Pro; Xaa at
residue 12 is Lys, N-methyl-Lys, N,N-dimethyl-Lys
or N, N,N-trimethyl-Lys.
<400> 194
Asp Ala Cys Cys Ser Asp Xaa. Arg Cys Ser Gly Xaa His Gln Asp Leu
1 5 10 15
Cys
<210> 195
CA 02361534 2002-02-22
87
<211> 17
<212> PRT
<213> Conus lividus
<220>
<221> PEPTIDE
<222> (1) .. (7)
<223> Xaa at residue 1 is Glu or gamma-carboxy-Glu; Xaa
at residue 7 is Pro or hydroxy-Pro.
<400> 195
Xaa Asp Cys Cys Ser Asp Xaa Arg Cys Ser Val Gly His Gln Asp Leu
1 5 10 15
Cys
<210> 196
<211> 16
<212> PRT
<213> Conus lividus
<220>
<221> PEPTIDE
<222> (6)
<223> Xaa at residue 6 is Pro or hydroxy-Pro.
<400> 196
Gly Cys Cys Ser His Xaa Ala Cys Ala Gly Ser Asn Ala His Ile Cys
1 5 10 15
<210> 197
<211> 17
<212> PRT
<213> Conus lividus
<220>
<221> PEPTIDE
<222> (1) .. (7)
<223> Xaa at residue 1 is Glu or gamma-carboxy-Glu; Xaa
at residue 7 is Pro or hydroxy-Pro.
<400> 197
Xaa Asp Cys Cys Ser Asp Xaa Arg Cys Ser Val Gly His Gln Asp Met
1 5 10 15
Cys
<210> 198
<211> 16
<212> PRT
CA 02361534 2002-02-22
88
<213> Conus lividus
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
<400> 198
Gly Cys Cys Ser His Xaa Ala Cys Ala Gly Asn Asn Xaa His Ile Cys
1 5 10 15
<210> 199
<211> 17
<212> PRT
<213> Conus lividus
<220>
<221> PEPTIDE
<222> (6)..(14)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 14 is Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr.
<400> 199
Gly Cys Cys Gly Asn Xaa Ser Cys Ser Ile His Ile Xaa Xaa Val Cys
1 5 10 15
Asn
<210> 200
<211> 21
<212> PRT
<213> Conus lividus
<220>
<221> PEPTIDE
<222> (4)..(5)
<223> Xaa at residues 4 and 5 is Glu or
gamma-carboxy-Glu.
<400> 200
Thr Asp Ser Xaa Xaa Cys Cys Leu Asp Ser Arg Cys Ala Gly Gln His
1 5 10 15
Gln Asp Leu Cys Gly
<210> 201
<211> 17
<212> PRT
CA 02361534 2002-02-22
89
<213> Conus marmoreus
<220>
<221> PEPTIDE
<222> (6)..(15)
<223> Xaa at residues 6 and 7 is Pro or hydroxy-Pro; Xaa
at residues 9 and 1!5 is Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-sulph.ho-Tyr, 0-phospho-Tyr or
nitro-Tyr.
<400> 201
Gly Cys Cys Ser Asn Xaa Xaa Cys Xaa Ala Asn Asn Gln Ala Xaa Cys
1 5 10 15
Asn
<210> 202
<211> 16
<212> PRT
<213> Conus marmoreus
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
<400> 202
Gly Cys Cys Ser His Xaa Ala Cys Ser Val Asn Asn Xaa Asp Ile Cys
1 5 10 15
<210> 203
<211> 18
<212> PRT
<213> Conus musicus
<220>
<221> PEPTIDE
<222> (2)..(15)
<223> Xaa at residues 2 and 12 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys; Xaa at
residue 14 is Pro or hydroxy-Pro.
<220>
<221> PEPTIDE
<222> (16)
<223> Xaa at residue 16 is Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-suipho-Tyr, O-phospho-Tyr or
nitro-Tyr.
<400> 203
Gly Xaa Cys Cys Ile Asn Asp Ala Cys Arg Ser Xaa His Xaa Gln Xaa
1 5 10 15
CA 02361534 2002-02-22
Cys Ser
<210> 204
<211> 17
<212> PRT
<213> Conus musicus
<220>
<221> PEPTIDE
<222> (4) .. (15)
<223> Xaa at residues 4 and 15 is Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, 0-sulpho-Tyr,
0-phospho-Tyr or nitro-Tyr; Xaa at residue 13 is
Pro or hydroxy-Pro.
<400> 204
Gly Cys Cys Xaa Asn Ile Ala Cys Arg Ile Asn Asn Xaa Arg Xaa Cys
1 5 10 15
Arg
<210> 205
<211> 17
<212> PRT
<213> Conus obscurus
<220>
<221> PEPTIDE
<222> (6)..(15)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residues 12 and 15 is Tyr, nor-Tyr,
mono-halo-Tyr, di halo-Tyr, O-sulpho-Tyr,
0-phospho-Tyr or nitro-Tyr.
<220>
<221> PEPTIDE
<222> (14)
<223> Xaa at residue 14 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<400> 205
Gly Cys Cys Ser His Xaa Val Cys Arg Phe Asn Xaa Xaa Xaa Xaa Cys
1 5 ]0 15
Gly
<210> 206
<211> 18
<212> PRT
CA 02361534 2002-02-22
91
<213> Conus obscurus
<220>
<221> PEPTIDE
<222> (2) .. (14)
<223> Xaa at residue 2 is Glu or gamma-carboxy-Glu; Xaa
at residues 7, 8 and 14 is Pro or hydroxy-Pro;
<220>
<221> PEPTIDE
<222> (15)
<223> Xaa at residue 15 is Tyr, nor-Tyr, mono-halo-Tyr, di-
halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr or nitro-Tyr.
<400> 206
Asp Xaa Cys Cys Ala Ser Xaa Xaa Cys Arg Leu Asn Asn Xaa Xaa Val
1 5 10 15
Cys His
<210> 207
<211> 19
<212> PRT
<213> Conus obscurus
<220>
<221> PEPTIDE
<222> (6)..(18)
<223> Xaa at residue 6 is Pro or hydroxy-Pro; Xaa at
residue 9 is Trp (D or L) or halo-Trp; Xaa at
residues 14 and 18 is Glu or gamma-carboxy-Glu.
<220>
<221> PEPTIDE
<222> (15)
<223> Xaa at residue 15 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr.
<400> 207
Gly Cys Cys Ser Asn Xaa Val Cys Xaa Gin Asn Asn Ala Xaa Xaa Cys
1 5 10 15
Arg Xaa Ser
<210> 208
<211> 16
<212> PRT
<213> Conus obscurus
<220>
CA 02361534 2002-02-22
92
<221> PEPTIDE
<222> (6)..(15)
<223> Xaa at residues 6 and 7 is Pro or hydroxy-Pro; Xaa
at residue 15 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr.
<400> 208
Gly Cys Cys Ser His Xaa Xaa Cys Ala Gin Asn Asn Gln Asp Xaa Cys
1 5 10 15
<210> 209
<211> 19
<212> PRT
<213> Conus obscurus
<220>
<221> PEPTIDE
<222> (6)..(18)
<223> Xaa at residue 6 is Pro or hydroxy-Pro; Xaa at
residues 14 and 18 is Glu or gamma-carboxy-Glu;
<220>
<221> PEPTIDE
<222> (15)
<223> Xaa at residue 15 is Tyr, nor-Tyr, mono-halo-Tyr, di-
halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr.
<400> 209
Gly Cys Cys Ser His Xaa A:La Cys Ser Gly Asn Asn Arg Xaa Xaa Cys
1 5 10 15
Arg Xaa Ser
<210> 210
<211> 18
<212> PRT
<213> Conus omaria
<220>
<221> PEPTIDE
<222> (2)..(14)
<223> Xaa at residues 2, 7 and 14 is Pro or hydroxy-Pro;
Xaa at residue 6 is, Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr.
<220>
<221> PEPTIDE
<222> (15)
<223> Xaa at residue 15 is Glu or gamma-carboxy-Glu.
CA 02361534 2002-02-22
93
<400> 210
Asp Xaa Cys Cys Ser Xaa Xaa Asp Cys Glr Ala Asn His Xaa Xaa Ile
1 5 10 15
Cys Gly
<210> 211
<211> 17
<212> PRT
<213> Conus omaria
<220>
<221> PEPTIDE
<222> (1)..(14)
<223> Xaa at residues 1 and 14 is Glu or
gamma-carboxy-Glu; Xaa at residues 6, 7 and 13 is
Pro or hydroxy-Pro; Xaa at residue 1.0 is Trp (D or
L) or halo-Trp.
<220>
<221> PEPTIDE
<222> (11)
<223> Xaa at residue 11 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<400> 211
Xaa Cys Cys Ser Gln Xaa Xaa Cys Arg Xaa Xaa His Xaa Xaa Leu Cys
1 5 10 15
Ser
<210> 212
<211> 16
<212> PRT
<213> Conus omaria
<220>
<221> PEPTIDE
<222> (6) .. (13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
<400> 212
Gly Cys Cys Ser His Xaa Ala Cys Ala Gly Asn Asn Xaa His Ile Cys
1 5 10 15
<210> 213
<211> 16
<212> PRT
<213> Conus omaria
CA 02361534 2002-02-22
94
<220>
<221> PEPTIDE
<222> (6)..(15)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 15 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-sulpho-Tyr, 0-phospho-Tyr or
nitro-Tyr.
<400> 213
Gly Cys Cys Ser Asp Xaa Ser Cys Asn Val Asn Asn Xaa Asp Xaa Cys
1 5 10 15
<210> 214
<211> 18
<212> PRT
<213> Conus omaria
<220>
<221> PEPTIDE
<222> (1)..(7)
<223> Xaa at residues 1 and 2 is Glu or
gamma-carboxy-Glu; Xaa at residue 7 is Pro or
hydroxy-Pro.
<400> 214
Xaa Xaa Cys Cys Ser Asp Xaa Arg Cys Ser Val Gly His Gln Asp Met
1 5 10 15
Cys Arg
<210> 215
<211> 17
<212> PRT
<213> Conus purpurascens
<220>
<221> PEPTIDE
<222> (7)..(15)
<223> Xaa at residue 7 is Pro or hydroxy-Pro; Xaa at
residue 15 is Glu or gamma-carboxy-Glu.
<400> 215
Gly Gly Cys Cys Ser Asn Xaa Ala Cys Leu Val Asn His Leu Xaa Met
1 5 10 15
Cys
<210> 216
<211> 18
<212> PRT
CA 02361534 2002-02-22
<213> Conus purpurascens
<220>
<221> PEPTIDE
<222> (3)..(15)
<223> Xaa at residues 3, 8 and 15 is Pro or hydroxy-Pro.
<400> 216
Arg Asp Xaa Cys Cys Phe Asn Xaa Ala Cys Asn Val Asn Asn Xaa Gln
1 5 1r) 15
Ile Cys
<210> 217
<211> 21
<212> PRT
<213> Conus purpurascens
<220>
<221> PEPTIDE
<222> (5) .. (8)
<223> Xaa at residue 5 is Pro or hydroxy-Pro; Xaa at
residue 8 is Trp (D or L) or halo-Trp.
<400> 217
Cys Cys Ser Asp Xaa Ser Cys Xaa Arg Leu His Ser Leu Ala Cys Thr
1 5 10 15
Gly Ile Val Asn Arg
<210> 218
<211> 16
<212> PRT
<213> Conus purpurascens
<220>
<221> PEPTIDE
<222> (5)
<223> Xaa at residue 5 is Pro or hydroxy-Pro.
<400> 218
Cys Cys Thr Asn Xaa Ala Cys Leu Val Asn Asri Ile Arg Phe Cys Gly
1 5 1.0 15
<210> 219
<211> 18
<212> PRT
<213> Conus regius
<220>
CA 02361534 2002-02-22
96
<221> PEPTIDE
<222> (2)..(7)
<223> Xaa at residue 2 is Glu or gamma-carboxy-Glu; Xaa
at residue 7 is Pro or hydroxy-Pro.
<400> 219
Asp Xaa Cys Cys Ser Asp Xaa Arg Cys His Gly Asn Asn Arg Asp His
1 5 10 15
Cys Ala
<210> 220
<211> 17
<212> PRT
<213> Conus regius
<220>
<221> PEPTIDE
<222> (6) .. (13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
<400> 220
Asp Cys Cys Ser His Xaa Leu Cys Arg Leu Phe Val Xaa Gly Leu Cys
1 5 10 15
Ile
<210> 221
<211> 17
<212> PRT
<213> Conus regius
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 9 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<220>
<221> PEPTIDE
<222> (12)
<223> Xaa at residue 12 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, O-sulpho-Tyr, 0-phospho-Tyr or
nitro-Tyr.
<400> 221
Gly Cys Cys Ser His Xaa Val Cys Xaa Val Arg Xaa Xaa Asp Leu Cys
1 5 10 15
Arg
CA 02361534 2002-02-22
97
<210> 222
<211> 16
<212> PRT
<213> Conus regius
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6"an.d 13 is Pro or hydroxy-Pro.
<400> 222
Gly Cys Cys Ser His Xaa Ala Cys Asn Val Asn Asn Xaa His Ile Cys
1 5 10 15
<210> 223
<211> 16
<212> PRT
<213> Conus regius
<220>
<221> PEPTIDE
<222> (6)..(12)
<223> Xaa at residue 6 is Pro or hydroxy-Pro; Xaa at
residue 12 is Tyr, nor-Tyr, nor-Tyr,
mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr,
O-phospho-Tyr or nitro-Tyr.
<220>
<221> PEPTIDE
<222> (9)
<223> Xaa at residue 9 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<400> 223
Gly Cys Cys Ser His Xaa Val Cys Xaa Val Arg Xaa Ser Asp Met Cys
1 5 10 15
<210> 224
<211> 17
<212> PRT
<213> Conus stercusmusca.rum
<220>
<221> PEPTIDE
<222> (7)..(14)
<223> Xaa at residues 7 and 14 is Pro or hydroxy-Pro;
Xaa at residue 10 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<400> 224
CA 02361534 2002-02-22
98
Gly Gly Cys Cys Ser His Xaa Ala Cys Xaa Val His Phe Xaa His Ser
1 5 10 15
Cys
<210> 225
<211> 20
<212> PRT
<213> Conus stercusmusca.rum
<220>
<221> PEPTIDE
<222> (6)..(14)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro;
Xaa at residue 14 is Glu or gamma-carboxy-Glu.
<400> 225
Val Cys Cys Ser Asn Xaa Val Cys His Val Asp His Xaa Xaa Leu Cys
1 5 10 15
Arg Arg Arg Arg
<210> 226
<211> 17
<212> PRT
<213> Conus striatus
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
<400> 226
Gly Cys Cys Ser His Xaa Val Cys Asn Leu Ser Asn Xaa Gln Ile Cys
1 5 10 15
Arg
<210> 227
<211> 18
<212> PRT
<213> Conus textile
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Xaa at residue 1 is Gin or pyro-Glu; Xaa at
residues 2 and 15 is Glu or gamma-carboxy-Glu; Xaa
at residues 7 and :L4 is Pro or hydroxy-Pro.
CA 02361534 2002-02-22
99
<400> 227
Xaa Xaa Cys Cys Ser His Xaa Ala Cys Asn Val Asp His Xaa Xaa Ile
1 5 10 15
Cys Arg
<210> 228
<211> 17
<212> PRT
<213> Conus tulipa
<220>
<221> PEPTIDE
<222> (6)
<223> Xaa at residue 6 is Pro or hydroxy-Pro.
<400> 228
Gly Cys Cys Ser Asn Xaa Ala Cys Leu Val Asn His Ile Arg Phe Cys
1 5 10 15
Gly
<210> 229
<211> 17
<212> PRT
<213> Conus virgo
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6 and 13 is Pro or hydroxy-Pro.
<400> 229
Asp Cys Cys Asp Asp Xaa Ala Cys Thr Val Asn Asn Xaa Gly Leu Cys
1 5 10 15
Thr
<210> 230
<211> 20
<212> PRT
<213> Conus textile
<220>
<221> PEPTIDE
<222> (6)..(13)
<223> Xaa at residues 6, 7 and 13 is Pro or hydroxy-Pro;
Xaa at residue 11 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
CA 02361534 2002-02-22
100
<400> 230
Gly Cys Cys Ser Asn Xaa Xaa Cys Ile Ala Xaa Asn Xaa His Met Cys
1 5 10 15
Gly Gly Arg Arg
<210> 231
<211> 18
<212> PRT
<213> Conus geographus
<220>
<221> PEPTIDE
<222> (5) .. (8)
<223> Xaa at residue 5 is Pro or hydroxy-Pro; Xaa at
residue 8 is Tyr, nor-Tyr, mono-halo-Tyr,
di-halo-Tyr, 0-sulpho-Tyr, O-phospho-Tyr or
nitro-Tyr.
<220>
<221> PEPTIDE
<222> (9)..(14)
<223> Xaa at residue 9 is Glu or gamma-carboxy--Glu; Xaa
at residues 10, 11, 12 and 14 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl--Lys.
<400> 231
Cys Cys Thr Ile Xaa Ser Cys Xaa Xaa Xaa Xaa Xaa Ile Xaa Ala Cys
1 5 10 15
Val Phe
<210> 232
<211> 18
<212> PRT
<213> Conus regius
<220>
<221> PEPTIDE
<222> (6)..(16)
<223> Xaa at residues 6 and 16 is Pro or hydroxy-Pro;
Xaa at residue 13 is Lys, N-methyl-Lys,
N,N-dimethyl-Lys or N,N,N-trimethyl-Lys.
<400> 232
Gly Cys Cys Gly Asn Xaa Ala Cys Ser Gly Ser Ser Xaa Asp Ala Xaa
1 5 10 15
Ser Cys
CA 02361534 2002-02-22
101
<210> 233
<211> 108
<212> DNA
<213> Conus imperialis
<220>
<221> CDS
<222> (1)..(105)
<400> 233
tct gat gga aag agt gcc gcg gcc aaa gcc aaa ccg tct cac ctg acg 48
Ser Asp Gly Lys Ser Ala Ala Ala Lys Ala Lys Pro Ser His Leu Thr
1 5 10 15
get cca ttc atc agg gac gaa tgc tgt tcc gat tct cgc tgt ggc aag 96
Ala Pro Phe Ile Arg Asp Glu Cys Cys Ser Asp Ser Arg Cys Gly Lys
20 25 30
aac tgt ctt tga 108
Asn Cys Leu
<210> 234
<211> 35
<212> PRT
<213> Conus imperialis
<400> 234
Ser Asp Gly Lys Ser Ala Ala Ala Lys Ala Lys Pro Ser His Leu Thr
1 5 10 15
Ala Pro Phe Ile Arg Asp G:1.u Cys Cys Ser Asp Ser Arg Cys Gly Lys
20 25 30
Asn Cys Leu
<210> 235
<211> 108
<212> DNA
<213> Conus imperialis
<220>
<221> CDS
<222> (1)..(105)
<400> 235
ttt gat gga agg aat gcc cca gcc gac gac aaa gcg tct gac ctg atc 48
Phe Asp Gly Arg Asn Ala Pro Ala Asp Asp Lys Ala Ser Asp Leu Ile
1 5 10 15
get caa atc gtc agg aga gca tgc tgt tcc gat cgt cgc tgt aga tgg 96
Ala Gin Ile Val Arg Arg Ala Cys Cys Ser Asp Arg Arg Cys Arg Trp
20 25 30
CA 02361534 2002-02-22
102
agg tgt ggt tga 108
Arg Cys Gly
<210> 236
<211> 35
<212> PRT
<213> Conus imperialis
<400> 236
Phe Asp Gly Arg Asn Ala Pro Ala Asp Asp Lys Ala Ser Asp Leu Ile
1 5 10 15
Ala Gln Ile Val Arg Arg A'-a Cys Cys Ser Asp Arg Arg Cys Arg Trp
20 25 30
Arg Cys Gly
<210> 237
<211> 145
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1)..(105)
<400> 237
tct gat gga agg aat gcc gca gcc gac gcc aga gcg tct ccc cgg atc 48
Ser Asp Gly Arg Asn Ala Ala Ala Asp Ala Arg Ala Ser Pro Arg Ile
1 5 10 15
get ctt ttc ctc agg ttc arc tgc tgt agg aga ggt acc tgt tcc cag 96
Ala Leu Phe Leu Arg Phe Thr Cys Cys Arg Arg Gly Thr Cys Ser Gln
20 25 30
cac tgt ggt tgaagacact gct:gctccag gaccctctga accacgacgt 145
His Cys Gly
<210> 238
<211> 35
<212> PRT
<213> Conus regius
<400> 238
Ser Asp Gly Arg Asn Ala A- - Ala Asp Ala Arg Ala Ser Pro Arg Ile
1 5 10 15
Ala Leu Phe Leu Arg Phe Thr Cys Cys Arg Arg Gly Thr Cys Ser Gln
20 25 30
CA 02361534 2002-02-22
103
His Cys Gly
<210> 239
<211> 145
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1)..(105)
<400> 239
tct aat gga agg aat gcc gca gcc gac gcc aaa gcg tct caa cgg atc 48
Ser Asn Gly Arg Asn Ala Ala Ala Asp Ala Lys Ala Ser Gln Arg Ile
1 5 10 15
get cca ttc ctc agg gac tat tgc tgt agg aga cat gcc tgt acg ttg 96
Ala Pro Phe Leu Arg Asp Tyr Cys Cys Arg Arg His Ala Cys Thr Leu
20 25 30
att tgt ggt tgaagacgct gctgctccag gaccctctga accacgacgt 145
Ile Cys Gly
<210> 240
<211> 35
<212> PRT
<213> Conus regius
<400> 240
Ser Asn Gly Arg Asn Ala Ala Ala Asp Ala Lys Ala Ser Gln Arg Ile
1 5 10 15
Ala Pro Phe Leu Arg Asp Tyr Cys Cys Arg Arg His Ala Cys Thr Leu
20 25 30
Ile Cys Gly
<210> 241
<211> 145
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1)..(105)
<400> 241
CA 02361534 2002-02-22
104
tct aat gga agg aat gcc gca gcc gac gcc aaa gcg tct caa cgg atc 48
Ser Asn Gly Arg Asn Ala Ala Ala Asp Ala Lys Ala Ser Gln Arg Ile
1 5 10 15
get cca ttc ctc agg gac tat tgc tgt agg aga cct ccc tgt acg ttg 96
Ala Pro Phe Leu Arg Asp Tyr Cys Cys Arg Arg Pro Pro Cys Thr Leu
20 25 30
att tgt ggt tgaagacgct gctgctccag gaccctctga accacgacgt 145
Ile Cys Gly
<210> 242
<211> 35
<212> PRT
<213> Conus regius
<400> 242
Ser Asn Gly Arg Asn Ala Ala Ala Asp Ala Lys Ala Ser Gln Arg Ile
1 5 10 15
Ala Pro Phe Leu Arg Asp Tyr Cys Cys Arg Arg Pro Pro Cys Thr Leu
20 25 30
Ile Cys Gly
<210> 243
<211> 136
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1)..(96)
<400> 243
tct aat aaa agg aag aat gcc gca atg ctt gac atg atc get caa cac 48
Ser Asn Lys Arg Lys Asn Ala Ala Met Leu Asp Met Ile Ala Gln His
1 5 10 15
gcc ata agg ggt tgc tgt tcc gat cct cgc tgt aga tat aga tgt cgt 96
Ala Ile Arg Gly Cys Cys Ser Asp Pro Arg Cys Arg Tyr Arg Cys Arg
20 25 30
tgaagacgct gctgctccag gaccctctga accacgacgt 136
<210> 244
<211> 32
<212> PRT
<213> Conus regius
CA 02361534 2002-02-22
105
<400> 244
Ser Asn Lys Arg Lys Asn Ala Ala Met Leu Asp Met Ile Ala Gln His
1 5 10 15
Ala Ile Arg Gly Cys Cys Ser Asp Pro Arg Cys Arg Tyr Arg Cys Arg
20 25 30
<210> 245
<211> 145
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1)..(105)
<400> 245
ttt aat gga agg agt gcc gca gcc gac caa aat gcg cct ggc ctg atc 48
Phe Asn Gly Arg Ser Ala Ala Ala Asp Gln Asn Ala Pro Gly Leu Ile
1 5 10 15
get caa gtc gtc aga gga ggg tgc tgt tcc gat ccc cgc tgc gcc tgg 96
Ala Gln Val Val Arg Gly Gly Cys Cys Ser Asp Pro Arg Cys Ala Trp
20 25 30
aga tgt ggt tgaagacgtt gct:gctccag gaccctctga accacgacgt 145
Arg Cys Gly
<210> 246
<211> 35
<212> PRT
<213> Conus regius
<400> 246
Phe Asn Gly Arg Ser Ala Ala Ala Asp Gln Asn Ala Pro Gly Leu Ile
1 5 10 15
Ala Gln Val Val Arg Gly Gay Cys Cys Ser Asp Pro Arg Cys Ala Trp
20 25 30
Arg Cys Gly
<210> 247
<211> 145
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1)..(105)
CA 02361534 2002-02-22
106
<400> 247
ttt gat gga agg aat gcc gca gcc gac gcc aaa gtg att aac acg gtc 48
Phe Asp Gly Arg Asn Ala Ala Ala Asp Ala Lys Val Ile Asn Thr Val
1 5 10 15
get cga atc gcc tgg gat ata tgc tgt tcc gaa cct gac tgt aac cat 96
Ala Arg Ile Ala Trp Asp Ile Cys Cys Ser Glu Pro Asp Cys Asn His
20 25 30
aaa tgt gtt tgaagacgct tctgctccag gaccctctga accacgacgt 145
Lys Cys Val
<210> 248
<211> 35
<212> PRT
<213> Conus regius
<400> 248
Phe Asp Gly Arg Asn Ala Ala Ala Asp Ala Lys Val Ile Asn Thr Val
1 5 10 15
Ala Arg Ile Ala Trp Asp Ile Cys Cys Ser Glu Pro Asp Cys Asn His
20 25 30
Lys Cys Val
<210> 249
<211> 136
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1)..(96)
<400> 249
tct aat aaa agg aag aat gcc gca atg ctt gac atg atc get caa cac 48
Ser Asn Lys Arg Lys Asn Ala. Ala Met Leu Asp Met Ile Ala Gln His
1 5 10 15
gcc ata agg ggt tgc tgt tcc gat cct cgc tgt aaa cat cag tgt ggt 96
Ala Ile Arg Gly Cys Cys Ser Asp Pro Arg Cys Lys His Gln Cys Gly
20 25 30
tgaagacgct gctgctccag gaccctctga accacgacgt 136
<210> 250
<211> 32
<212> PRT
<213> Conus regius
<400> 250
CA 02361534 2002-02-22
107
Ser Asn Lys Arg Lys Asn Ala Ala Met Leu Asp Met Ile Ala Gln His
1 5 10 15
Ala Ile Arg Gly Cys Cys Ser Asp Pro Arg Cys Lys His Gln Cys Gly
20 25 30
<210> 251
<211> 136
<212> DNA
<213> Conus musicus
<220>
<221> CDS
<222> (1)..(105)
<400> 251
atc aag aat aca gca gcc aqc aac aaa gcg tct agc ctg gtg get ctt 48
Ile Lys Asn Thr Ala Ala Ser Asn Lys Ala Ser Ser Leu Val Ala Leu
1 5 10 15
gtt gtc agg gga tgc tgt tac aat cct gtc tgc aag aaa tat tat tgt 96
Val Val Arg Gly Cys Cys Tyr Asn Pro Val Cys Lys Lys Tyr Tyr Cys
20 25 30
tgg aaa ggc tgatgctcca ggaccctctg aaccacgacg t 136
Trp Lys Gly
<210> 252
<211> 35
<212> PRT
<213> Conus musicus
<400> 252
Ile Lys Asn Thr Ala Ala Ser Asn Lys Ala Ser Ser Leu Val Ala Leu
1 5 10 15
Val Val Arg Gly Cys Cys Tyr Asn Pro Val Cys Lys Lys Tyr Tyr Cys
20 25 30
Trp Lys Gly
<210> 253
<211> 148
<212> DNA
<213> Conus purpurascens
<220>
<221> CDS
<222> (1)..(117)
CA 02361534 2002-02-22
108
<400> 253
tct gaa ggc agg aat get gaa gcc atc gac aac gcc tta gac cag agg 48
Ser Glu Gly Arg Asn Ala G:Lu Ala Ile Asp Asn Ala Leu Asp Gln Arg
1 5 10 15
gat cca aag cga cag gag ccg ggg tgc tgt agg cat cct gcc tgt ggg 96
Asp Pro Lys Arg Gln Glu Pro Gly Cys Cys Arg His Pro Ala Cys Gly
20 25 30
aag aac aga tgt gga aga cgc tgatgctcca ggaccctctg aaccacgacg t 148
Lys Asn Arg Cys Gly Arg Arg
<210> 254
<211> 39
<212> PRT
<213> Conus purpurascens
<400> 254
Ser Glu Gly Arg Asn Ala Glu Ala Ile Asp Asn Ala Leu Asp Gln Arg
1 5 10 15
Asp Pro Lys Arg Gln Glu Pro Giy Cys Cys Arg His Pro Ala Cys Gly
20 25 30
Lys Asn Arg Cys Gly Arg Arg
<210> 255
<211> 156
<212> DNA
<213> Conus musicus
<220>
<221> CDS
<222> (1)..(102)
<400> 255
tct gat ggc agg aat att gca gtc gac gac aga tgg tct ttc tat acg 48
Ser Asp Gly Arg Asn Ile Ala Val Asp Asp Arg Trp Ser Phe Tyr Thr
1 5 10 15
ctc ttc cat get act tgc tgt gcc gat cct gac tgt aga ttc cgg ccc 96
Leu Phe His Ala Thr Cys Cys Ala Asp Pro Asp Cys Arg Phe Arg Pro
20 25 30
ggt tgt tgatctttgt tcttcaaaga cgctgctggc ccaggaccct ctgaaccacg 152
Gly Cys
acgt 156
<210> 256
<211> 34
CA 02361534 2002-02-22
109
<212> PRT
<213> Conus musicus
<400> 256
Ser Asp Gly Arg Asn Ile Ala Val Asp Asp Arg Trp Ser Phe Tyr Thr
1 5 10 15
Leu Phe His Ala Thr Cys Cys Ala Asp Pro Asp Cys Arg Phe Arg Pro
20 25 30
Gly Cys
<210> 257
<211> 142
<212> DNA
<213> Conus musicus
<220>
<221> CDS
<222> (1) .. (102)
<400> 257
atc aag aat act gca gcc agc aac aaa gcg cct agc ctg gtg get att 48
Ile Lys Asn Thr Ala Ala Ser Asn Lys Ala Pro Ser Leu Val Ala Ile
1 5 10 15
gcc gtc agg gga tgc tgt tac aat cct tcc tgt tgg ccg aaa aca tat 96
Ala Val Arg Gly Cys Cys Tyr Asn Pro Ser Cys Trp Pro Lys Thr Tyr
20 25 30
tgt agt tggaaaggct gatgctccag gaccctctga accacgacgt 142
Cys Ser
<210> 258
<211> 34
<212> PRT
<213> Conus musicus
<400> 258
Ile Lys Asn Thr Ala Ala Ser Asn Lys Ala Pro Ser Leu Val Ala Ile
1 5 10 15
Ala Val Arg Gly Cys Cys Tyr Asn Pro Ser Cys Trp Pro Lys Thr Tyr
20 25 30
Cys Ser
<210> 259
<211> 161
<212> DNA
CA 02361534 2002-02-22
110
<213> Conus musicus
<220>
<221> CDS
<222> (1)..(108)
<400> 259
tct gat agc agg aat gtc gca atc gag gac aga gtg tct gac ctg cac 48
Ser Asp Ser Arg Asn Val Ala Ile Glu Asp Arg Val Ser Asp Leu His
1 5 10 15
tct atg ttc ttc gat gtt tot tgc tgt agc aat cct acc tgt aaa gaa 96
Ser Met Phe Phe Asp Val Seer Cys Cys Ser Asn Pro Thr Cys Lys Glu
20 25 30
acg tat ggt tgt tgatcgttgq ttttgaagac gctgatgctc caggaccctc 148
Thr Tyr Gly Cys
tgaaccacga cgt 161
<210> 260
<211> 36
<212> PRT
<213> Conus musicus
<400> 260
Ser Asp Ser Arg Asn Val A.1.a Ile Glu Asp Arg Val Ser Asp Leu His
1 5 10 15
Ser Met Phe Phe Asp Val Ser Cys Cys Ser Asn Pro Thr Cys Lys Glu
20 25 30
Thr Tyr Gly Cys
<210> 261
<211> 156
<212> DNA
<213> Conus musicus
<220>
<221> CDS
<222> (1)..(102)
<400> 261
tct gtt ggc agg aat att gca gtc gac gac aga ggg att ttc tct acg 48
Ser Val Gly Arg Asn Ile Ala Val Asp Asp Arg Gly Ile Phe Ser Thr
1 5 10 15
ctc ttc cat get cat tgc tgt gcc aat ccc atc tgt aaa aac acg ccc 96
Leu Phe His Ala His Cys Cys Ala Asn Pro Ile Cys Lys Asn Thr Pro
20 25 30
CA 02361534 2002-02-22
111
ggt tgt tgatctttgt tcttcaaaga cgctgctggc ccaggaccct ctgaaccacg 152
Gly Cys
acgt 156
<210> 262
<211> 34
<212> PRT
<213> Conus musicus
<400> 262
Ser Val Gly Arg Asn Ile Ala Val Asp Asp Arg Gly Ile Phe Ser Thr
1 5 10 15
Leu Phe His Ala His Cys Cys Ala Asn Pro Ile Cys Lys Asn Thr Pro
20 25 30
Gly Cys
<210> 263
<211> 161
<212> DNA
<213> Conus musicus
<220>
<221> CDS
<222> (1)..(108)
<400> 263
tcc gat ggc agg aat gtc gca atc gac gac aga gtg tct gac ctg cac 48
Ser Asp Gly Arg Asn Val Ala Ile Asp Asp Arg Val Ser Asp Leu His
1 5 10 15
tct atg ttc ttc gat att get tgc tgt aac aat cct acc tgt aaa gaa 96
Ser Met Phe Phe Asp Ile Ala Cys Cys Asn Asn Pro Thr Cys Lys Glu
20 25 30
acg tat ggt tgt tgatcgttgg ttttgaagac gctgatgctc caggaccctc 148
Thr Tyr Gly Cys
tgaaccacga cgt 161
<210> 264
<211> 36
<212> PRT
<213> Conus musicus
<400> 264
Ser Asp Gly Arg Asn Val Ala Ile Asp Asp Arg Val Ser Asp Leu His
1 5 10 15
CA 02361534 2002-02-22
112
Ser Met Phe Phe Asp Ile Ala Cys Cys Asn Asn Pro Thr Cys Lys Glu
20 25 30
Thr Tyr Gly Cys
<210> 265
<211> 161
<212> DNA
<213> Conus musicus
<220>
<221> CDS
<222> (1)..(108)
<400> 265
tct gat ggc agg aat gtc gca atc gag gac aga gtg tct gac ctg ctc 48
Ser Asp Gly Arg Asn Val Ala Ile Glu Asp Arg Val Ser Asp Leu Leu
1 5 1,0 15
tct atg ctc ttc gat gtt get tgc tgt agc aat cct gtc tgt aaa gaa 96
Ser Met Leu Phe Asp Val Ala Cys Cys Ser Asn Pro Val Cys Lys Glu
20 25 30
acg tat ggt tgt tgatcgttgg ttttgaagac gctgatgctc caggaccctc 148
Thr Tyr Gly Cys
tgaaccacga cgt 161
<210> 266
<211> 36
<212> PRT
<213> Conus musicus
<400> 266
Ser Asp Gly Arg Asn Val Ala Ile Glu Asp Arg Val Ser Asp Leu Leu
1 5 1() 15
Ser Met Leu Phe Asp Val Ala Cys Cys Ser Asn Pro Val Cys Lys Glu
20 25 30
Thr Tyr Gly Cys
<210> 267
<211> 154
<212> DNA
<213> Conus betulinus
<220>
<221> CDS
CA 02361534 2002-02-22
113
<222> (1)..(123)
<400> 267
tat gat ggc agg aat get gcc gcc gac gac aaa get ttt gac ctg ctg 48
Tyr Asp Gly Arg Asn Ala Ala Ala Asp Asp Lys Ala Phe Asp Leu Leu
1 5 10 15
get atg acc ata agg gga gga tgc tgt tcc tat cct ccc tgt atc gcg 96
Ala Met Thr Ile Arg Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala
20 25 30
agt aat cct aaa tgt ggt gga aga cgc tgatgctcca ggaccctctg 143
Ser Asn Pro Lys Cys Gly Gly Arg Arg
35 40
aaccacaacg t 154
<210> 268
<211> 41
<212> PRT
<213> Conus betulinus
<400> 268
Tyr Asp Gly Arg Asn Ala Ala Ala Asp Asp Lys Ala Phe Asp Leu Leu
1 5 10 15
Ala Met Thr Ile Arg Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala
20 25 30
Ser Asn Pro Lys Cys Gly G:ly Arg Arg
35 40
<210> 269
<211> 151
<212> DNA
<213> Conus lividus
<220>
<221> CDS
<222> (1)..(111)
<400> 269
ttt gat ggc agg aat get gc.a ggc aac gcc aaa atg tcc gcc ctg atg 48
Phe Asp Gly Arg Asn Ala Ala Gly Asn Ala Lys Met Ser Ala Leu Met
1 5 10 15
gcc ctg acc atc agg gga tgc tgt tcc cat cct gtc tgt agc gcg atg 96
Ala Leu Thr Ile Arg Gly Cys Cys Ser His Pro Val Cys Ser Ala Met
20 25 30
agt cca atc tgt ggc tgaagacgct gatgccccag gaccctctga accacgacgt 151
Ser Pro Ile Cys Gly
CA 02361534 2002-02-22
114
<210> 270
<211> 37
<212> PRT
<213> Conus lividus
<400> 270
Phe Asp Gly Arg Asn Ala Ala Gly Asn Ala Lys Met Ser Ala Leu Met
1 5 10 15
Ala Leu Thr Ile Arg Gly Cys Cys Ser His Pro Val Cys Ser Ala Met
20 25 30
Ser Pro Ile Cys Gly
<210> 271
<211> 196
<212> DNA
<213> Conus musicus
<220>
<221> CDS
<222> (1)..(165)
<400> 271
atc aag aat get gca get gac gac aaa gca tct gac ctg ctc tct cag 48
Ile Lys Asn Ala Ala Ala Asp Asp Lys Ala Ser Asp Leu Leu Ser Gln
1 5 10 15
atc gtc agg aat get gca tcc aat gac aaa ggg tct gac ctg atg act 96
Ile Val Arg Asn Ala Ala Ser Asn Asp Lys Gly Ser Asp Leu Met Thr
20 25 30
ctt gcc ctc agg gga tgc tgt aaa aat cct tac tgt ggt gcg tcg aaa 144
Leu Ala Leu Arg Gly Cys Cys Lys Asn Pro Tyr Cys Gly Ala Ser Lys
35 40 45
aca tat tgt ggt aga aga cgc tgatgctcca ggaccctctg aaccacgacg t 196
Thr Tyr Cys Gly Arg Arg Arg
so (:;5
<210> 272
<211> 55
<212> PRT
<213> Conus musicus
<400> 272
Ile Lys Asn Ala Ala Ala Asp Asp Lys Ala Ser Asp Leu Leu Ser Gln
1 5 10 15
Ile Val Arg Asn Ala Ala Ser Asn Asp Lys Gly Ser Asp Leu Met Thr
20 25 30
CA 02361534 2002-02-22
115
Leu Ala Leu Arg Gly Cys Cys Lys Asn Pro Tyr Cys Gly Ala Ser Lys
35 40 45
Thr Tyr Cys Gly Arg Arg Arg
50 5`i
<210> 273
<211> 139
<212> DNA
<213> Conus omaria
<220>
<221> CDS
<222> (40)..(108)
<400> 273
tctgatggca ggaatgccgc agcgtctgac ctgatggat ctg acc atc aag gga 54
Leu Thr Ile Lys Gly
1 5
tgc tgt tct tat cct ccc tgt ttc gcg act aat cca gac tgt ggt cga 102
Cys Cys Ser Tyr Pro Pro Cys Phe Ala Thr Asn Pro Asp Cys Gly Arg
15 20
cga cgc tgatgctcca ggaccct:ctg aaccacgacg t 139
Arg Arg
<210> 274
<211> 23
<212> PRT
<213> Conus omaria
<400> 274
Leu Thr Ile Lys Gly Cys Cys Ser Tyr Pro Pro Cys Phe Ala Thr Asn
1 5 10 15
Pro Asp Cys Gly Arg Arg Arg
<210> 275
<211> 126
<212> DNA
<213> Conus radiatus
<220>
<221> CDS
<222> (1) .. (123)
<400> 275
ttt gat ggc agg aat gcc gca gcc gac tac aaa ggg tct gaa ttg ctc 48
Phe Asp Gly Arg Asn Ala Ala Ala Asp Tyr Lys Gly Ser Glu Leu Leu
1 5 10 15
CA 02361534 2002-02-22
116
get atg acc gtc agg gga gga tgc tgt tcc tat cct ccc tgt atc gca 96
Ala Met Thr Val Arg Gly G1y Cys Cys Ser Tyr Pro Pro Cys Ile Ala
20 25 30
aat aat cct ctt tgt get gga aga cgc tga 126
Asn Asn Pro Leu Cys Ala Gly Arg Arg
35 40
<210> 276
<211> 41
<212> PRT
<213> Conus radiatus
<400> 276
Phe Asp Gly Arg Asn Ala Ala Ala Asp Tyr Lys Gly Ser Glu Leu Leu
1 5 10 15
Ala Met Thr Val Arg Gly Gly Cys Cys Ser Tyr Pro Pro Cys Ile Ala
20 25 30
Asn Asn Pro Leu Cys Ala Gly Arg Arg
3S 40
<210> 277
<211> 126
<212> DNA
<213> Conus radiatus
<220>
<221> CDS
<222> (1)..(123)
<400> 277
ttt gat ggc agg aat gcc gca gcc gac tac aaa ggg tct gaa ttg ctc 48
Phe Asp Gly Arg Asn Ala Ala Ala Asp Tyr Lys Gly Ser Glu Leu Leu
1 5 10 15
get atg acc gtc agg gga gga tgc tgt tcc tat cct ccc tgt atc gca 96
Ala Met Thr Val Arg Gly Sly Cys Cys Ser Tyr Pro Pro Cys Ile Ala
20 25 30
aat aat cct ttt tgt get gga aga cgc tga 126
Asn Asn Pro Phe Cys Ala Gly Arg Arg
35 40
<210> 278
<211> 41
<212> PRT
<213> Conus radiatus
<400> 278
Phe Asp Gly Arg Asn Ala Ala Ala Asp Tyr Lys Gly Ser Glu Leu Leu
1 5 10 15
CA 02361534 2002-02-22
117
Ala Met Thr Val Arg Gly Gl.y Cys Cys Ser Tyr Pro Pro Cys Ile Ala
20 25 30
Asn Asn Pro Phe Cys Ala Gly Arg Arg
35 40
<210> 279
<211> 155
<212> DNA
<213> Conus virgo
<220>
<221> CDS
<222> (1)..(114)
<400> 279
tct tat gac agg tat gcc tcg ccc gtc gac aga gcg tct gcc ctg atc 48
Ser Tyr Asp Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser Ala Leu Ile
1 5 1() 15
get cag gcc atc ctt cga gat tgc tgt tcc aat cct ccc tgt tcc caa 96
Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro Cys Ser Gln
20 25 30
aat aat cca gac tgt atg taaagacgct gcttgctcca ggaccctctg 144
Asn Asn Pro Asp Cys Met
aaccacgacg t 155
<210> 280
<211> 38
<212> PRT
<213> Conus virgo
<400> 280
Ser Tyr Asp Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser Ala Leu Ile
1 5 10 15
Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro Cys Ser Gln
20 25 30
Asn Asn Pro Asp Cys Met
<210> 281
<211> 155
<212> DNA
<213> Conus virgo
CA 02361534 2002-02-22
118
<220>
<221> CDS
<222> (1) (114)
<400> 281
tct tat ggc agg tat gcc tca ccc gtc gac aga gcg tct gcc ctg atc 48
Ser Tyr Gly Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser Ala Leu Ile
1 5 10 15
get cag gcc atc ctt cga gat tgc tgc tcc aat cct cct tgt gcc cat 96
Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro Cys Ala His
20 25 30
aat aat cca gac tgt cgt taaagacgct gcttgctcca ggaccctctg 144
Asn Asn Pro Asp Cys Arg
aaccacgacg t 155
<210> 282
<211> 38
<212> PRT
<213> Conus virgo
<400> 282
Ser Tyr Gly Arg Tyr Ala Ser Pro Val Asp Arg Ala Ser Ala Leu Ile
1 5 10 15
Ala Gln Ala Ile Leu Arg Asp Cys Cys Ser Asn Pro Pro Cys Ala His
20 25 30
Asn Asn Pro Asp Cys Arg
<210> 283
<211> 126
<212> DNA
<213> Conus achatinus
<220>
<221> CDS
<222> (1)..(123)
<400> 283
tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct ggc atg agc 48
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Gly Met Ser
1 5 10 15
gcg ctg gcc gtc aat gaa tgc tgt acc aac cct gtc tgt cac gcg gaa 96
Ala Leu Ala Val Asn Glu Cys Cys Thr Asn Pro Val Cys His Ala Glu
20 25 30
cat caa gaa ctt tgt get aga aga cgc tga 126
His Gln Glu Leu Cys Ala Arg Arg Arg
35 40
CA 02361534 2002-02-22
119
<210> 284
<211> 41
<212> PRT
<213> Conus achatinus
<400> 284
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Gly Met Ser
1 5 10 15
Ala Leu Ala Val Asn Glu Cys Cys Thr Asn Pro Val Cys His Ala Glu
20 25 30
His Gln Glu Leu Cys Ala Arg Arg Arg
35 40
<210> 285
<211> 126
<212> DNA
<213> Conus achatinus
<220>
<221> CDS
<222> (1)..(123)
<400> 285
tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct gac gtg atc 48
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Val Ile
1 5 10 15
acg ctg gcc ctc aag gga tc{c tgt tcc aac cct gtc tgt cac ttg gag 96
Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn Pro Val Cys His Leu Glu
20 25 30
cat tca aac ctt tgt ggt aga aga cgc tga 126
His Ser Asn Leu Cys Gly Arg Arg Arg
35 40
<210> 286
<211> 41
<212> PRT
<213> Conus achatinus
<400> 286
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Val Ile
1 5 10 15
Thr Leu Ala Leu Lys Gly Cys Cys Ser Asn Pro Val Cys His Leu Glu
20 25 30
CA 02361534 2002-02-22
120
His Ser Asn Leu Cys Gly Arg Arg Arg
35 40
<210> 287
<211> 126
<212> DNA
<213> Conus achatinus
<220>
<221> CDS
<222> (1)..(123)
<400> 287
tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct ggc atg agc 48
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Gly Met Ser
1 5 10 15
gcg ctg gcc gtc aat gaa tqc. tgt acc aac cct gtc tgt cac gtg gaa 96
Ala Leu Ala Val Asn Glu Cys Cys Thr Asn Pro Val Cys His Val Glu
20 25 30
cat caa gaa ctt tgt get aga aga cgc tga 126
His Gln Glu Leu Cys Ala Arg Arg Arg
35 40
<210> 288
<211> 41
<212> PRT
<213> Conus achatinus
<400> 288
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Gly Met Ser
1 5 10 15
Ala Leu Ala Val Asn Glu Cys Cys Thr Asn Pro Val Cys His Val Glu
20 25 30
His Gln Glu Leu Cys Ala Arg Arg Arg
35 40
<210> 289
<211> 220
<212> DNA
<213> Conus ammiralis
<220>
<221> CDS
<222> (1)..(180)
<400> 289
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Lou Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
CA 02361534 2002-02-22
121
ttc act tca gat cgt gca ttt cgt ggc agg aat gcc gca gcc aaa gcg 96
Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
tct ggc ctg gtc ggt ctg acc gac aag agg caa gaa tgc tgt tct tat 144
Ser Gly Leu Val Gly Leu Thr Asp Lys Arg Gln Glu Cys Cys Ser Tyr
35 40 45
cct gcc tgt aac cta gat cat cca gaa ctt tgt ggt tgaagacgct 190
Pro Ala Cys Asn Leu Asp His Pro Glu Leu Cys Gly
50 55 60
gatgctccag gaccctctga accacgacgt 220
<210> 290
<211> 60
<212> PRT
<213> Conus ammiralis
<400> 290
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Asp Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys Ala
20 25 30
Ser Gly Leu Val Gly Leu Thr Asp Lys Arg Gln Glu Cys Cys Ser Tyr
35 40 45
Pro Ala Cys Asn Leu Asp His Pro Glu Leu Cys Gly
50 55 60
<210> 291
<211> 223
<212> DNA
<213> Conus ammiralis
<220>
<221> CDS
<222> (1)..(192)
<400> 291
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc act gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
tcc act tca ggt cgt cgt gca ttt cgt ggc agg aat gcc gca gcc aaa 96
Ser Thr Ser Gly Arg Arg Ala Phe Arg Gly Arg Asn Ala Ala Ala Lys
20 25 30
gcg tct gga ctg gtc ggt ctg act gac agg aga cca gaa tgc tgt agt 144
Ala Ser Gly Leu Val Gly Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser
35 40 45
CA 02361534 2002-02-22
122
gat cct cgc tgt aac tcg act cat cca gaa ctt tgt ggt gga aga cgc 192
Asp Pro Arg Cys Asn Ser Thr. His Pro Glu Leu Cys Gly Gly Arg Arg
50 55 60
tgatgctcca ggaccctctg aaccacgacg t 223
<210> 292
<211> 64
<212> PRT
<213> Conus ammiralis
<400> 292
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Ser Thr Ser Gly Arg Arg A:La Phe Arg Gly Arg Asn Ala Ala Ala Lys
20 25 30
Ala Ser Gly Leu Val Gly Leu Thr Asp Arg Arg Pro Glu Cys Cys Ser
35 40 45
Asp Pro Arg Cys Asn Ser Thr His Pro Glu Leu Cys Gly Gly Arg Arg
50 55 60
<210> 293
<211> 151
<212> DNA
<213> Conus arenatus
<220>
<221> CDS
<222> (1)..(120)
<400> 293
tct gat ggc agg aat gcc gca gcc aac gcg ttt gac ctg atc gat ctg 48
Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Phe Asp Leu Ile Asp Leu
1 5 10 15
acc gcc agg cta aat tgc tgt atg att ccc ccc tgt tgg aag aaa tat 96
Thr Ala Arg Leu Asn Cys Cys Met Ile Pro Pro Cys Trp Lys Lys Tyr
20 25 30
gga gac aga tgt agt gaa gta cgc tgatgctcca ggaccctctg aaccacgacg 150
Gly Asp Arg Cys Ser Glu Val Arg
35 40
t 151
<210> 294
<211> 40
<212> PRT
<213> Conus arenatus
CA 02361534 2002-02-22
123
<400> 294
Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Phe Asp Leu Ile Asp Leu
1 5 10 15
Thr Ala Arg Leu Asn Cys Cys Met Ile Pro Pro Cys Trp Lys Lys Tyr
20 25 30
Gly Asp Arg Cys Ser Glu Val Arg
35 40
<210> 295
<211> 126
<212> DNA
<213> Conus arenatus
<220>
<221> CDS
<222> (1)..(93)
<400> 295
tct gat ggc agg aat gcc gca cgc aaa gcg ttt ggc tgc tgc gac tta 48
Ser Asp Gly Arg Asn Ala Ala Arg Lys Ala Phe Gly Cys Cys Asp Leu
1 5 10 15
ata ccc tgt ttg gag aga tat ggt aac aga tgt aat gaa gtg cac 93
Ile Pro Cys Leu Glu Arg Tyr Gly Asn Arg Cys Asn Glu Val His
20 25 30
tgatgctcca ggaccctctg aaccacgcga cgt 126
<210> 296
<211> 31
<212> PRT
<213> Conus arenatus
<400> 296
Ser Asp Gly Arg Asn Ala Ala Arg Lys Ala Phe Gly Cys Cys Asp Leu
1 5 10 15
Ile Pro Cys Leu Glu Arg Tyr Gly Asn Arg Cys Asn Glu Val His
20 25 30
<210> 297
<211> 151
<212> DNA
<213> Conus arenatus
<220>
<221> CDS
<222> (1)..(120)
<400> 297
tct gat ggc agc aat gcc gca gcc aac gag ttt gac ctg atc get ctg 48
Ser Asp Gly Ser Asn Ala Ala Ala Asn Glu Phe Asp Leu Ile Ala Leu
1 5 10 15
CA 02361534 2002-02-22
124
acc gcc agg cta ggt tgc tgt aac gtt aca ccc tgt tgg gag aaa tat 96
Thr Ala Arg Leu Gly Cys Cys Asn Val Thr Pro Cys Trp Glu Lys Tyr
20 25 30
gga gac aaa tgt aat gaa gta cgc tgatgcttca ggaccctctg aaccacgacg 150
Gly Asp Lys Cys Asn Glu Val Arg
35 40
t 151
<210> 298
<211> 40
<212> PRT
<213> Conus arenatus
<400> 298
Ser Asp Gly Ser Asn Ala Ala Ala Asn Glu Phe Asp Leu Ile Ala Leu
1 5 10 15
Thr Ala Arg Leu Gly Cys Cys Asn Val Thr Pro Cys Trp Glu Lys Tyr
20 25 30
Gly Asp Lys Cys Asn Glu Val Arg
35 40
<210> 299
<211> 148
<212> DNA
<213> Conus arenatus
<220>
<221> CDS
<222> (1)..(117)
<400> 299
tct gat ggc agg aat gtc gca gca aaa gcg ttt cac cgg atc ggc cgg 48
Ser Asp Gly Arg Asn Val Ala Ala Lys Ala Phe His Arg Ile Gly Arg
1 5 1.0 15
acc atc agg gat gaa tgc tgt tcc aat cct gcc tgt agg gtg aat aat 96
Thr Ile Arg Asp Glu Cys Cys Ser Asn Pro A:La Cys Arg Val Asn Asn
20 25 30
cca cac gtt tgt aga cga cgc tgatgctcca ggaccctctg aaccacgacg t 148
Pro His Val Cys Arg Arg Arg
<210> 300
<211> 39
CA 02361534 2002-02-22
125
<212> PRT
<213> Conus arenatus
<400> 300
Ser Asp Gly Arg Asn Val Ala Ala Lys Ala Phe His Arg Ile Gly Arg
1 5 10 15
Thr Ile Arg Asp Glu Cys Cys Ser Asn Pro Ala Cys Arg Val Asn Asn
20 25 30
Pro His Val Cys Arg Arg Arg
<210> 301
<211> 151
<212> DNA
<213> Conus arenatus
<220>
<221> CDS
<222> (1)..(120)
<400> 301
tct gat ggc agg aat gcc gca gcc aac gcg ttt gac ctg atg cct ctg 48
Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Phe Asp Leu Met Pro Leu
1 5 10 15
acc gcc agg cta aat tgc tgt agc att ccc ggc tgt tgg aac gaa tat 96
Thr Ala Arg Leu Asn Cys Cys Ser Ile Pro Gly Cys Trp Asn Glu Tyr
20 25 30
aaa gac aga tgt agt aaa gta cgc tgatgctcca ggaccctctg aaccacgacg 150
Lys Asp Arg Cys Ser Lys Val Arg
35 40
t 151
<210> 302
<211> 40
<212> PRT
<213> Conus arenatus
<400> 302
Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Phe Asp Leu Met Pro Leu
1 5 10 15
Thr Ala Arg Leu Asn Cys Cys Ser Ile Pro Gly Cys Trp Asn Glu Tyr
20 25 30
Lys Asp Arg Cys Ser Lys Val Arg
35 40
CA 02361534 2002-02-22
126
<210> 303
<211> 157
<212> DNA
<213> Conus aurisiacus
<220>
<221> CDS
<222> (52)..(126)
<400> 303
tctgatggca ggaatgccgc agccgacgac aaagcgtctg acctggtcgc t ctg gtc 57
Leu Val
1
gtc agg gga gga tgc tgt tcc cac cct gtc tgt tac ttt aat aat cca 105
Val Arg Gly Gly Cys Cys Ser His Pro Val Cys Tyr Phe Asn Asn Pro
10 1.5
caa atg tgt cgt gga aga cgc tgatgctcca ggaccctctg aaccacgacg t 157
Gin Met Cys Arg Gly Arg Arg
20 25
<210> 304
<211> 25
<212> PRT
<213> Conus aurisiacus
<400> 304
Leu Val Val Arg Gly Gly Cys Cys Ser His Pro Val Cys Tyr Phe Asn
1 5 10 15
Asn Pro Gln Met Cys Arg Gly Arg Arg
20 25
<210> 305
<211> 157
<212> DNA
<213> Conus aurisiacus
<220>
<221> CDS
<222> (52)..(126)
<400> 305
tctgatggca ggaatgccgc agccgacgac aaagcgtctg acctggtcgc t ctg gcc 57
Leu Ala
1
gtc agg gga gga tgc tgt tcc cac cct gtc tgt aac ttg aat aat cca 105
Val Arg Gly Gly Cys Cys Ser His Pro Val Cys Asn Leu Asn Asn Pro
5 10 15
caa atg tgt cgt gga aga cgc tgatgctcca ggaccctctg aaccacgacg t 157
Gln Met Cys Arg Gly Arg A.rg
20 25
CA 02361534 2002-02-22
127
<210> 306
<211> 25
<212> PRT
<213> Conus aurisiacus
<400> 306
Leu Ala Val Arg Gly Gly Cys Cys Ser His Pro Val Cys Asn Leu Asn
1 5 10 15
Asn Pro Gln Met Cys Arg Gly Arg Arg
20 25
<210> 307
<211> 157
<212> DNA
<213> Conus betulinus
<220>
<221> CDS
<222> (1)..(117)
<400> 307
ttt cgt ggc agg aat ccc gca gcc aac gac aaa agg tct gac ctg gcc 48
Phe Arg Gly Arg Asn Pro Ala Ala Asn Asp Lys Arg Ser Asp Leu Ala
1 5 10 15
get ctg agc gtc agg gga gga tgc tgt tcc cat cct gcc tgt agc gtg 96
Ala Leu Ser Val Arg Gly Gly Cys Cys Ser His Pro Ala Cys Ser Val
20 25 30
act cat cca gag ctt tgt ggc tgaagacgct gatgccccag gaccctctga 147
Thr His Pro Glu Leu Cys Gly
accacgacgt 157
<210> 308
<211> 39
<212> PRT
<213> Conus betulinus
<400> 308
Phe Arg Gly Arg Asn Pro Ala Ala Asn Asp Lys Arg Ser Asp Leu Ala
1 5 1.0 15
Ala Leu Ser Val Arg Gly Gly Cys Cys Ser His Pro Ala Cys Ser Val
20 25 30
Thr His Pro Glu Leu Cys Gly
CA 02361534 2002-02-22
1,28
<210> 309
<211> 151
<212> DNA
<213> Conus betulinus
<220>
<221> CDS
<222> (1)..(120)
<400> 309
tct gat ggc ggg aat gcc gca gcc aaa gcg tct gac ctg atc get cag 48
Ser Asp Gly Gly Asn Ala Ala Ala Lys Ala Ser Asp Leu Ile Ala Gln
1 5 10 15
acc atc agg gga gga tgc tgt tcc tat cct gcc tgt agc gtg gaa cat 96
Thr Ile Arg Gly Gly Cys Cys Ser Tyr Pro Ala Cys Ser Val Glu His
20 25 30
caa gac ctt tgt gat gga aga cgc tgatgctcca ggaccctctg aaccacgacg 150
Gln Asp Leu Cys Asp Gly Arg Arg
35 40
t 151
<210> 310
<211> 40
<212> PRT
<213> Conus betulinus
<400> 310
Ser Asp Gly Gly Asn Ala Ala Ala Lys Ala Ser Asp Leu Ile Ala Gln
1 5 10 15
Thr Ile Arg Gly Gly Cys Cys Ser Tyr Pro Ala Cys Ser Val Glu His
20 25 30
Gln Asp Leu Cys Asp Gly Arg Arg
35 40
<210> 311
<211> 114
<212> DNA
<213> Conus caracterist:i.cus
<220>
<221> CDS
<222> (1)..(111)
<400> 311
tct tat ggc agg aat gcc gca gcc aaa gcg ttt gaa gtg agt tgc tgt 48
Ser Tyr Gly Arg Asn Ala Ala Ala Lys Ala Phe Glu Val Ser Cys Cys
1 5 10 15
CA 02361534 2002-02-22
129
gtc gtt cgc ccc tgt tgg att cgc tat caa gag gaa tgt ctt gaa gca 96
Val Val Arg Pro Cys Trp Ile Arg Tyr Gln Glu Glu Cys Leu Glu Ala
20 25 30
gat ccc agg acc ctc tga 114
Asp Pro Arg Thr Leu
<210> 312
<211> 37
<212> PRT
<213> Conus caracteristicus
<400> 312
Ser Tyr Gly Arg Asn Ala Ala Ala Lys Ala Phe Glu Val Ser Cys Cys
1 5 10 15
Val Val Arg Pro Cys Trp Ile Arg Tyr Gln Glu Glu Cys Leu Glu Ala
20 25 30
Asp Pro Arg Thr Leu
<210> 313
<211> 123
<212> DNA
<213> Conus caracteristicus
<220>
<221> CDS
<222> (1) .. (120)
<400> 313
tct gat ggc agg aat gcc gca gcc aac gcc ct.t gac ctg atc act ctg 48
Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Leu Asp Leu Ile Thr Leu
1 5 1 () 15
atc gcc agg caa aat tgc tgt agc att ccc ggc tgt tgg gag aaa tat 96
Ile Ala Arg Gln Asn Cys Cys Ser Ile Pro Gly Cys Trp Glu Lys Tyr
20 25 30
gga gac aaa tgt agt gaa gta cgc tga 123
Gly Asp Lys Cys Ser Glu Val Arg
35 40
<210> 314
<211> 40
<212> PRT
<213> Conus caracteristicus
CA 02361534 2002-02-22
130
<400> 314
Ser Asp Gly Arg Asn Ala Ala Ala Asn Ala Leu Asp Leu Ile Thr Leu
1 5 10 15
Ile Ala Arg Gln Asn Cys Cys Ser Ile Pro Gly Cys Trp Glu Lys Tyr
20 25 30
Gly Asp Lys Cys Ser Glu Val Arg
35 40
<210> 315
<211> 154
<212> DNA
<213> Conus catus
<220>
<221> CDS
<222> (1)..(123)
<400> 315
tct gat ggc agg aat gaa gca gcc aac gac gaa gcg tct gac gtg atc 48
Ser Asp Gly Arg Asn Glu Ala Ala Asn Asp Glu Ala Ser Asp Val Ile
1 5 10 15
gag ctg gcc ctc aag gga tgc tgt tcc aac cct gtc tgt cac ttg gag 96
Glu Leu Ala Leu Lys Gly Cys Cys Ser Asn Pro Val Cys His Leu Glu
20 25 30
cat cca aac get tgt ggt aqa aga cgc tgatgctcca ggaccctctg 143
His Pro Asn Ala Cys Gly Arg Arg Arg
35 40
aaccacgacg t 154
<210> 316
<211> 41
<212> PRT
<213> Conus catus
<400> 316
Ser Asp Gly Arg Asn Glu Ala Ala Asn Asp Glu Ala Ser Asp Val Ile
1 5 10 15
Glu Leu Ala Leu Lys Gly Cys Cys Ser Asn Pro Val Cys His Leu Glu
20 25 30
His Pro Asn Ala Cys Gly Arg Arg Arg
35 40
<210> 317
<211> 154
<212> DNA
<213> Conus catus
CA 02361534 2002-02-22
131
<220>
<221> CDS
<222> (1) (123)
<400> 317
tct gat ggc agg aat gcc gca gcc aac gac aaa gcg tct gac ctg gtc 48
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Val
1 5 10 15
get ctg gcc gtc agg gga tgc tgt tcc aac cct atc tgt tac ttt aat 96
Ala Leu Ala Val Arg Gly Cys Cys Ser Asn Pro Ile Cys Tyr Phe Asn
20 25 30
aat cca cga att tgt cgt gga aga cgc tgatgctcca ggaccctctg 143
Asn Pro Arg Ile Cys Arg Gly Arg Arg
35 40
aaccacgacg t 154
<210> 318
<211> 41
<212> PRT
<213> Conus catus
<400> 318
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Val
1 5 10 15
Ala Leu Ala Val Arg Gly Cys Cys Ser Asn Pro Ile Cys Tyr Phe Asn
20 25 30
Asn Pro Arg Ile Cys Arg Gly Arg Arg
35 40
<210> 319
<211> 111
<212> DNA
<213> Conus episcopatus
<220>
<221> CDS
<222> (1)..(108)
<400> 319
tct cat ggc agg aat gcc gca cgc aaa gcg tct gac ctg atc get ctg 48
Ser His Gly Arg Asn Ala Ala Arg Lys Ala Ser Asp Leu Ile Ala Leu
1 5 10 15
acc gtc agg gaa tgc tgt tct cag cct ccc tgt cgc tgg aaa cat cca 96
Thr Val Arg Glu Cys Cys Ser Gln Pro Pro Cys Arg Trp Lys His Pro
20 25 30
CA 02361534 2002-02-22
132
gaa ctt tgt agt tga ill
Glu Leu Cys Ser
<210> 320
<211> 36
<212> PRT
<213> Conus episcopatus
<400> 320
Ser His Gly Arg Asn Ala Ala Arg Lys Ala Ser Asp Leu Ile Ala Leu
1 5 10 15
Thr Val Arg Glu Cys Cys Ser Gln Pro Pro Cys Arg Trp Lys His Pro
20 25 30
Glu Leu Cys Ser
<210> 321
<211> 151
<212> DNA
<213> Conus geographus
<220>
<221> CDS
<222> (1)..(120)
<400> 321
tct gat ggc agg aat gac gca gcc aaa gcg ttt gac ctg ata tct tcg 48
Ser Asp Gly Arg Asn Asp Ala Ala Lys Ala Phe Asp Leu Ile Ser Ser
1 5 10 15
acc gtc aag aaa gga tgc tgt tcc cat cct gcc tgt gcg ggg aat aat 96
Thr Val Lys Lys Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn Asn
20 25 30
caa cat att tgt ggc cga aga cgc tgatgctcca ggaccctctg aaccacgacg 150
Gln His Ile Cys Gly Arg Arg Arg
35 40
t 151
<210> 322
<211> 40
<212> PRT
<213> Conus geographus
<400> 322
Ser Asp Gly Arg Asn Asp Ala Ala Lys Ala Phe Asp Leu Ile Ser Ser
1 5 10 15
CA 02361534 2002-02-22
133
Thr Val Lys Lys Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn Asn
20 25 30
Gln His Ile Cys Gly Arg Arg Arg
35 40
<210> 323
<211> 154
<212> DNA
<213> Conus geographus
<220>
<221> CDS
<222> (1)..(123)
<400> 323
tct gat ggc agg aat gcc gca gcc aac gac caa gcg tct gac ctg atg 48
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Gln Ala Ser Asp Leu Met
1 5 10 15
get gcg acc gtc agg gga tgc tgt gcc gtt cct tcc tgt cgc ctc cgt 96
Ala Ala Thr Val Arg Gly Cys Cys Ala Val Pro Ser Cys Arg Leu Arg
20 25 30
aat cca gac ctt tgt ggt gga gga cgc tgatgctcca ggaccctctg 143
Asn Pro Asp Leu Cys Gly Gly Gly Arg
35 40
aaccacgacg t 154
<210> 324
<211> 41
<212> PRT
<213> Conus geographus
<400> 324
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Gln Ala Ser Asp Leu Met
1 5 10 15
Ala Ala Thr Val Arg Gly Cys Cys Ala Val Pro Ser Cys Arg Leu Arg
20 25 30
Asn Pro Asp Leu Cys Gly Gly Gly Arg
35 40
<210> 325
<211> 120
<212> DNA
<213> Conus imperialis
<220>
<221> CDS
<222> (1)..(117)
CA 02361534 2002-02-22
134
<400> 325
ctt gat gaa agg aat gcc gca gcc gac gac aaa gcg tct gac ctg atc 48
Leu Asp Glu Arg Asn Ala Ala Ala Asp Asp Lys Ala Ser Asp Leu Ile
1 5 10 15
get caa atc gtc agg aga gga tgc tgt tcc cat cct gcc tgt aac gtg 96
Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Ala Cys Asn Val
20 25 30
aat aat cca cac att tgt ggt tga 120
Asn Asn Pro His Ile Cys Gly
<210> 326
<211> 39
<212> PRT
<213> Conus imperialis
<400> 326
Leu Asp Glu Arg Asn Ala Ala Ala Asp Asp Lys Ala Ser Asp Leu Ile
1 5 10 15
Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Ala Cys Asn Val
20 25 30
Asn Asn Pro His Ile Cys Gly
<210> 327
<211> 142
<212> DNA
<213> Conus lividus
<220>
<221> CDS
<222> (1)..(111)
<400> 327
tct gat ggc agg aat act gca gcc aaa gtc aaa tat tct aag acg ccg 48
Ser Asp Gly Arg Asn Thr Ala Ala Lys Val Lys Tyr Ser Lys Thr Pro
1 5 10 15
gag gaa tgc tgt ccc aat cct ccc tgt ttc gcg aca aat tcg gat att 96
Glu Glu Cys Cys Pro Asn Pro Pro Cys Phe Ala Thr Asn Ser Asp Ile
20 25 30
tgt ggc gga aga cgc tgatgctcca ggaccctctg aaccacgacg t 142
Cys Gly Gly Arg Arg
<210> 328
<211> 37
CA 02361534 2002-02-22
135
<212> PRT
<213> Conus lividus
<400> 328
Ser Asp Gly Arg Asn Thr Ala Ala Lys Val Lys Tyr Ser Lys Thr Pro
1 5 10 15
Glu Glu Cys Cys Pro Asn Pro Pro Cys Phe Ala Thr Asn Ser Asp Ile
20 25 30
Cys Gly Gly Arg Arg
<210> 329
<211> 157
<212> DNA
<213> Conus lividus
<220>
<221> CDS
<222> (1)..(117)
<400> 329
tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg 48
Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met
1 5 10 15
aag cgg acc gtc agg gat gct tgc tgt tca gac cct cgc tgt tcc ggg 96
Lys Arg Thr Val Arg Asp Ala Cys Cys Ser Asp Pro Arg Cys Ser Gly
20 25 30
aaa cat caa gac ctg tgt ggc tgaagacgct gat:gctccag gaccctctga 147
Lys His Gln Asp Leu Cys Gly
accacgacgt 157
<210> 330
<211> 39
<212> PRT
<213> Conus lividus
<400> 330
Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met
1 5 10 15
Lys Arg Thr Val Arg Asp Ala Cys Cys Ser Asp Pro Arg Cys Ser Gly
20 25 30
Lys His Gln Asp Leu Cys Gly
<210> 331
CA 02361534 2002-02-22
136
<211> 157
<212> DNA
<213> Conus lividus
<220>
<221> CDS
<222> (1)..(117)
<400> 331
tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg 48
Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met
1 5 10 15
gag ctg acc gtc agg gaa gat tgC tgt tca gac cct cgc tgt tcc gtg 96
Glu Leu Thr Val Arg Glu Asp Cys Cys Ser Asp Pro Arg Cys Ser Val
20 25 30
gga cat caa gac ctg tgt ggc tgaagacgct gatgctccag gaccctctga 147
Gly His Gln Asp Leu Cys Gly
accacgacgt 157
<210> 332
<211> 39
<212> PRT
<213> Conus lividus
<400> 332
Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met
1 5 10 15
Glu Leu Thr Val Arg Glu Asp Cys Cys Ser Asp Pro Arg Cys Ser Val
20 25 30
Gly His Gln Asp Leu Cys Gly
<210> 333
<211> 157
<212> DNA
<213> Conus lividus
<220>
<221> CDS
<222> (1) .. (126)
<400> 333
gca ttt gat ggc agg aat get gca gcc agc gac aaa gcg tcc gag ctg 48
Ala Phe Asp Gly Arg Asn Ala Ala Ala Ser Asp Lys Ala Ser Glu Leu
1 5 10 15
atg get ctg gcc gtc agg gga tgc tgt tcc cat cct gcc tgt get ggg 96
Met Ala Leu Ala Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly
20 25 30
CA 02361534 2002-02-22
137
agt aat gca cat atc tgt ggc aga aga cgc tgatgctcca ggaccctctg 146
Ser Asn Ala His Ile Cys Gly Arg Arg Arq_
35 40
aaccacgacg t 157
<210> 334
<211> 42
<212> PRT
<213> Conus lividus
<400> 334
Ala Phe Asp Gly Arg Asn Ala. Ala Ala Ser Asp Lys Ala Ser Glu Leu
1 5 10 15
Met Ala Leu Ala Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly
20 25 30
Ser Asn Ala His Ile Cys Gly Arg Arg Arg
35 40
<210> 335
<211> 157
<212> DNA
<213> Conus lividus
<220>
<221> CDS
<222> (1)..(117)
<400> 335
tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg 48
Ser Asn Gly Arg Asn Ala A:La Ala Lys Phe Lys Ala Pro Ala Leu Met
1 5 10 15
aag ctg acc gtc agg gag gat tgc tgt tca gac cct cgc tgt tcc gtg 96
Lys Leu Thr Val Arg Glu Asp Cys Cys Ser Asp Pro Arg Cys Ser Val
20 25 30
gga cat caa gac atg tgt ggc tgaagacgct gatgctccag gaccctctga 147
Gly His Gin Asp Met Cys Gly
atcacgacgt 157
<210> 336
<211> 39
<212> PRT
<213> Conus lividus
CA 02361534 2002-02-22
138
<400> 336
Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met
1 5 10 15
Lys Leu Thr Val Arg Glu Asp Cys Cys Ser Asp Pro Arg Cys Ser Val
20 25 30
Gly His Gln Asp Met Cys Giy
<210> 337
<211> 154
<212> DNA
<213> Conus lividus
<220>
<221> CDS
<222> (1) .. (114)
<400> 337
ttt gaa tgc agg aat get gca ggc aac gac aaa gcg act gac ctg atg 48
Phe Glu Cys Arg Asn Ala Ala Gly Asn Asp Lys Ala Thr Asp Leu Met
1 5 10 15
get ctg act gtc agg gga tgc tgt tcc cat cct gcc tgt get ggg aat 96
Ala Leu Thr Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn
20 25 30
aat cca cat atc tgc ggc tgaagacgct gatgctccag gaccctctga 144
Asn Pro His Ile Cys Gly
accacgacgt 154
<210> 338
<211> 38
<212> PRT
<213> Conus lividus
<400> 338
Phe Glu Cys Arg Asn Ala Ala Gly Asn Asp Lys Ala Thr Asp Leu Met
1 5 10 15
Ala Leu Thr Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn
20 25 30
Asn Pro His Ile Cys Gly
<210> 339
<211> 154
<212> DNA
CA 02361534 2002-02-22
139
<213> Conus lividus
<220>
<221> CDS
<222> (1)..(114)
<400> 339
ttt gat ggc agg aac gcc gca gcc aac aac aaa gcg act gat ctg atg 48
Phe Asp Gly Arg Asn Ala Ala Ala Asn Asn Lys Ala Thr Asp Leu Met
1 5 1O 15
get ctg act gtc aga gga tgc tgt ggc aat cct tca tgt agc atc cat 96
Ala Leu Thr Val Arg Gly Cys Cys Gly Asn Pro Ser Cys Ser Ile His
20 25 30
att cct tac gtt tgt aat tagagacact gatgctccag gaccctctga 144
Ile Pro Tyr Val Cys Asn
accacgacgt 154
<210> 340
<211> 38
<212> PRT
<213> Conus lividus
<400> 340
Phe Asp Gly Arg Asn Ala Ala Ala Asn Asn Lys Ala Thr Asp Leu Met
1 5 10 15
Ala Leu Thr Val Arg Gly Cys Cys Gly Asn Pro Ser Cys Ser Ile His
20 25 30
Ile Pro Tyr Val Cys Asn
<210> 341
<211> 157
<212> DNA
<213> Conus lividus
<220>
<221> CDS
<222> (1)..(126)
<400> 341
tct aat ggc agg aat gcc gca gcc aaa ttc aaa gcg cct gcc ctg atg 48
Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met
1 5 15
aag cgg acc gac agc gaa gaa tgc tgt tta gac tct cgc tgt gcc ggg 96
Lys Arg Thr Asp Ser Glu Glu Cys Cys Leu Asp Ser Arg Cys Ala Gly
20 25 30
CA 02361534 2002-02-22
140
caa cat caa gac ctg tgt ggc gga aga cgc tgatgctcca ggaccctctg 146
Gln His Gln Asp Leu Cys Gly Gly Arg Arg
35 40
aaccacgacg t 157
<210> 342
<211> 42
<212> PRT
<213> Conus lividus
<400> 342
Ser Asn Gly Arg Asn Ala Ala Ala Lys Phe Lys Ala Pro Ala Leu Met
1 5 10 15
Lys Arg Thr Asp Ser Glu Glu Cys Cys Leu Asp Ser Arg Cys Ala Gly
20 25 30
Gln His Gln Asp Leu Cys Gly Gly Arg Arg
35 40
<210> 343
<211> 126
<212> DNA
<213> Conus marmoreus
<220>
<221> CDS
<222> (1)..(123)
<400> 343
tct at ggc agg aat gcc gca gcc aag gac aaa gcg tct gac ctg gtc 48
Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp Lys Ala Ser Asp Leu Val
1 5 10 15
get ctg acc gtc aag gga tcgc tgt tct aat cct ccc tgt tac gcg aat 96
Ala Leu Thr Val Lys Gly Cys Cys Ser Asn Pro Pro Cys Tyr Ala Asn
20 25 30
aat caa gcc tat tgt aat gga aga cgc tga 126
Asn Gln Ala Tyr Cys Asn Gly Arg Arg
35 40
<210> 344
<211> 41
<212> PRT
<213> Conus marmoreus
<400> 344
Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp Lys Ala Ser Asp Leu Val
1 5 1.0 15
CA 02361534 2002-02-22
14:1
Ala Leu Thr Val Lys Gly Cys Cys Ser Asn Pro Pro Cys Tyr Ala Asn
20 25 30
Asn Gln Ala Tyr Cys Asn Sly Arg Arg
35 40
<210> 345
<211> 117
<212> DNA
<213> Conus marmoreus
<220>
<221> CDS
<222> (1)..(114)
<400> 345
tct gat ggc agg aat gcc gca gcc aag gac aaa gcg tct gac ctg gtc 48
Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp Ly's Ala Ser Asp Leu Val
1 5 10 15
get ctg acc gtc aag gga tgc tgt t.ct cat cct gcc tgt agc gtg aat 96
Ala Leu Thr Val Lys Gly Cys Cys Set His Pro Ala Cys Ser Val Asn
20 25 30
aat cca gac att tgt ggt tc{a 117
Asn Pro Asp Ile Cys Gly
<210> 346
<211> 38
<212> PRT
<213> Conus marmoreus
<400> 346
Ser Asp Gly Arg Asn Ala Ala Ala Lys Asp Lys Ala Ser Asp Leu Val
1 5 10 15
Ala Leu Thr Val Lys Gly Cys Cys Ser His Pro Ala Cys Ser Val Asn
20 25 30
Asn Pro Asp Ile Cys Gly
<210> 347
<211> 145
<212> DNA
<213> Conus musicus
<220>
<221> CDS
<222> (1)..(114)
<400> 347
CA 02361534 2002-02-22
142
tct gat ggc agg aat get gca gcc aac aac aaa gtg get ttg acc atg 48
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asn Lys Val Ala Leu Thr Met
1 5 10 15
agg gga aaa tgc tgt atc aat gat gcg tgt cgc tcg aaa cat cca cag 96
Arg Gly Lys Cys Cys Ile Asn Asp Ala Cys Arg Ser Lys His Pro Gln
20 25 30
tac tgt tct gga aga cgc tgatattcca ggaccctctg aaccacgacg t 145
Tyr Cys Ser Gly Arg Arg
<210> 348
<211> 38
<212> PRT
<213> Conus musicus
<400> 348
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asn Lys Val Ala Leu Thr Met
1 5 1 () 15
Arg Gly Lys Cys Cys Ile Asn Asp Ala Cys Arg Ser Lys His Pro Gln
20 25 30
Tyr Cys Ser Gly Arg Arg
<210> 349
<211> 154
<212> DNA
<213> Conus musicus
<220>
<221> CDS
<222> (1)..(123)
<400> 349
tct gat ggc agg aat get gca gcc aac gac aaa gtg tct gac cag atg 48
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Val Ser Asp Gln Met
1 5 1O 15
get ctg gtt gtc agg gga tgc tgt tac aat att gcc tgt aga att aat 96
Ala Leu Val Val Arg Gly Cys Cys Tyr Asn Ile Ala Cys Arg Ile Asn
20 25 30
aat cca cgg tac tgt cgt gga aaa cgc tgatgttcca ggaccctctg 143
Asn Pro Arg Tyr Cys Arg Gly Lys Arg
35 40
aaccacgacg t 154
<210> 350
CA 02361534 2002-02-22
143
<211> 41
<212> PRT
<213> Conus musicus
<400> 350
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Val Ser Asp Gln Met
1 5 10 15
Ala Leu Val Val Arg Gly Cys Cys Tyr Asn Ile Ala Cys Arg Ile Asn
20 25 30
Asn Pro Arg Tyr Cys Arg Gly Lys Arg
35 40
<210> 351
<211> 154
<212> DNA
<213> Conus obscurus
<220>
<221> CDS
<222> (52)..(123)
<400> 351
tctgaaggca ggaatgccgc agccaacgac aaagcgtctg acctgatggc t ctg aac 57
Leu Asn
1
gtc agg gga tgc tgt tcc cat cct gtc tgt cgc ttc aat tat cca aaa 105
Val Arg Gly Cys Cys Ser His Pro Val Cys Arg Phe Asn Tyr Pro Lys
10 15
tat tgt ggt gga aga cgc tgatggtcca ggaccctctg aaccacgacg t 154
Tyr Cys Gly Gly Arg Arg
<210> 352
<211> 24
<212> PRT
<213> Conus obscurus
<400> 352
Leu Asn Val Arg Gly Cys Cys Ser His Pro Val Cys Arg Phe Asn Tyr
1 5 10 15
Pro Lys Tyr Cys Gly Gly Arg Arg
<210> 353
<211> 151
<212> DNA
<213> Conus obscurus
CA 02361534 2002-02-22
14:4
<220>
<221> CDS
<222> (46)..(111)
<400> 353
tctgatggcg ggaatgccgc agcaaaagcg tttgatctaa tcact ctg gcc ctc agg 57
Leu Ala Leu Arg
1
gat gaa tgc tgt gcc agt cct ccc tgt cgt ttg aat aat cca tac gta 105
Asp Glu Cys Cys Ala Ser Pro Pro Cys Arg Leu Asn Asn Pro Tyr Val
10 15 20
tgt cat tgacgacgct gatgctccag gaccctctga accacgacgt 151
Cys His
<210> 354
<211> 22
<212> PRT
<213> Conus obscurus
<400> 354
Leu Ala Leu Arg Asp Glu Cys Cys Ala Ser Pro Pro Cys Arg Leu Asn
1 5 10 15
Asn Pro Tyr Val Cys His
<210> 355
<211> 217
<212> DNA
<213> Conus obscurus
<220>
<221> CDS
<222> (1)..(186)
<400> 355
atg ttc acc gtg ttt ctg tt:g gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leeu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ccc act tca gat cgt gca tot gat agg agg aat gcc gca gcc aaa gcg 96
Pro Thr Ser Asp Arg Ala Seer Asp Arg Arg Asn Ala Ala Ala Lys Ala
20 25 30
ttt gac ctg aga tat tcg acc gcc aag aga gga tgc tgt tcc aat cct 144
Phe Asp Leu Arg Tyr Ser Thr. Ala Lys Arg Gly Cys Cys Ser Asn Pro
35 40 45
gtc tgt tgg cag aat aat gca gaa tac tgt cgt gaa agt ggc 186
Val Cys Trp Gln Asn Asn Ala Glu Tyr Cys Arg Glu Ser Gly
5o 55 60
CA 02361534 2002-02-22
145
taatgctcca ggaccctctg aaccacgacg t 217
<210> 356
<211> 62
<212> PRT
<213> Conus obscurus
<400> 356
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Pro Thr Ser Asp Arg Ala Ser Asp Arg Arg Asn Ala Ala Ala Lys Ala
20 25 30
Phe Asp Leu Arg Tyr Ser Thr Ala Lys Arg Gly Cys Cys Ser Asn Pro
35 40 45
Val Cys Trp Gln Asn Asn Ala Glu Tyr Cys Arg Glu Ser Gly
50 55 60
<210> 357
<211> 208
<212> DNA
<213> Conus obscurus
<220>
<221> CDS
<222> (1)..(168)
<400> 357
atg ttc acc gtg ttt ctg ttg gtt gtc ttg gca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Leu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
ttc act tca gat cgt gca tct gat ggc ggg aat gtc gca gcg tct cac 96
Phe Thr Ser Asp Arg Ala Ser Asp Gly Gly Asn Val Ala Ala Ser His
20 25 30
ctg atc get ctg acc atc aag gga tgc tgt tct cac cct ccc tgt gcc 144
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Ala
35 40 45
cag aat aat caa gac tat tgt ggt tgacgacgct gatgctccag gaccctctga 198
Gin Asn Asn Gln Asp Tyr Cys Gly
50 55
accacgacgt 208
<210> 358
<211> 56
<212> PRT
<213> Conus obscurus
CA 02361534 2002-02-22
146
<400> 358
Met Phe Thr Val Phe Leu Letu Val Val Leu Ala Thr Thr Val Val Ser
1 5 10 15
Phe Thr Ser Asp Arg Ala Sear Asp Gly Gly Asn Val Ala Ala Ser His
20 25 30
Leu Ile Ala Leu Thr Ile Lys Gly Cys Cys Ser His Pro Pro Cys Ala
35 40 45
Gln Asn Asn Gln Asp Tyr Cys Gly
50 55
<210> 359
<211> 217
<212> DNA
<213> Conus obscurus
<220>
<221> CDS
<222> (1)..(186)
<400> 359
atg ttc acc gtg ttt ctg tt:g gtt gtc tta tca acc acc gtc gtt tcc 48
Met Phe Thr Val Phe Leu Levu Val Val Leu Ser Thr Thr Val Val Ser
1 5 10 15
tcc act tca gat cgt gca tct gat agg agg aat gcc gca gcc aaa gcg 96
Ser Thr Ser Asp Arg Ala Se>.r. Asp Arg Arg Asn Ala Ala Ala Lys Ala
20 25 30
tct gac ctg atg tat tcg acc gtc aag aaa gga tgt tgt tcc cat cct 144
Ser Asp Leu Met Tyr Ser Thr Val Lys Lys Gly Cys Cys Ser His Pro
35 40 45
gcc tgt tcg ggg aat aat cqa gaa tat tgt cgt gaa agt ggc 186
Ala Cys Ser Gly Asn Asn Arg Glu Tyr Cys Arg Glu Ser Gly
50 55 60
taatgctcca ggaccctctg aaccacgacg t 217
<210> 360
<211> 62
<212> PRT
<213> Conus obscurus
<400> 360
Met Phe Thr Val Phe Leu Leu Val Val Leu Ser Thr Thr Val Val Ser
1 5 10 15
Ser Thr Ser Asp Arg Ala Soar Asp Arg Arg Asn Ala Ala Ala Lys Ala
20 25 30
CA 02361534 2002-02-22
147
Ser Asp Leu Met Tyr Ser Thr Val Lys Lys Gly Cys Cys Ser His Pro
35 40 45
Ala Cys Ser Gly Asn Asn Arg Glu Tyr Cys Arg Glu Ser Gly
50 555 60
<210> 361
<211> 157
<212> DNA
<213> Conus omaria
<220>
<221> CDS
<222> (52)..(126)
<400> 361
tttgatggca ggaatgcctc agccgacagc aaagtggctg cccggatcgc t cag atc 57
Gln Ile
1
gac agg gat cca tgc tgt tcc tat cct gac tgt ggc gcg aat cat cca 105
Asp Arg Asp Pro Cys Cys Ser Tyr Pro Asp Cys Gly Ala Asn His Pro
10 1.5
gag att tgt ggt gga aaa cclc tgatgctcca ggaccctctg aaccacgacg t 157
Glu Ile Cys Gly Gly Lys Arg
20 25
<210> 362
<211> 25
<212> PRT
<213> Conus omaria
<400> 362
Gln Ile Asp Arg Asp Pro Cys Cys Ser Tyr Pro Asp Cys Gly Ala Asn
1 5 10 15
His Pro Glu Ile Cys Gly Gly Lys Arg
20 25
<210> 363
<211> 128
<212> DNA
<213> Conus omaria
<220>
<221> CDS
<222> (26) .. (88)
<400> 363
tctcatggca ggaatgccgc acgct ctg acc gtc agg gaa tgc tgt tct cag 52
Leu Thr Val Arg Glu Cys Cys Ser Gln
1 5
CA 02361534 2002-02-22
148
cct cct tgt cgc tgg aaa cat cca gaa ctt tgt agt tgaagacgct 98
Pro Pro Cys Arg Trp Lys His Pro Glu Leu Cys Ser
15 20
gatgctccag gaccctctga accacgacgt 128
<210> 364
<211> 21
<212> PRT
<213> Conus omaria
<400> 364
Leu Thr Val Arg Glu Cys Cys Ser Gln Pro Pro Cys Arg Trp Lys His
1 5 10 15
Pro Glu Leu Cys Ser
<210> 365
<211> 154
<212> DNA
<213> Conus omaria
<220>
<221> CDS
<222> (52)..(123)
<400> 365
tttgatggca ggaatgctgc agccagcgac aaagcgtctg agctgatggc t ctg gcc 57
Leu Ala
1
gtc agg gga tgc tgt tcc cat cct gcc tgt get ggg aat aat cca cat 105
Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn Asn Pro His
5 10 15
atc tgt ggc aga aga cgc tq_atgctcca ggaccctctg aaccacgacg t 154
Ile Cys Gly Arg Arg Arg
<210> 366
<211> 24
<212> PRT
<213> Conus omaria
<400> 366
Leu Ala Val Arg Gly Cys Cys Ser His Pro Ala Cys Ala Gly Asn Asn
1 5 10 15
Pro His Ile Cys Gly Arg Arg Arg
CA 02361534 2002-02-22
149
<210> 367
<211> 142
<212> DNA
<213> Conus omaria
<220>
<221> CDS
<222> (40)..(102)
<400> 367
tctggtgtca ggaaagacgc agcgcctggc ctgatcgct ctg acc atc aag gga 54
Leu Thr Ile Lys Gly
1 5
tgc tgt tct gat cct agc tgt aac gtg aat aat cca gac tat tgt ggt 102
Cys Cys Ser Asp Pro Ser Cys Asn Val Asn Asn Pro Asp Tyr Cys Gly
15 20
tgacgacgct gatgctccag gaccctctga accacgacgt 142
<210> 368
<211> 21
<212> PRT
<213> Conus omaria
<400> 368
Leu Thr Ile Lys Gly Cys Cys Ser Asp Pro Ser Cys Asn Val Asn Asn
1 5 10 15
Pro Asp Tyr Cys Gly
<210> 369
<211> 157
<212> DNA
<213> Conus omaria
<220>
<221> CDS
<222> (52)..(117)
<400> 369
tctaatggca ggaatgccgc agccaaattc aaagcgcct:g ccctgatgga g ctg acc 57
Leu Thr
1
gtc agg gaa gaa tgc tgt tca gac cct cgc tgt tcc gtg gga cat caa 105
Val Arg Glu Glu Cys Cys Ser Asp Pro Arg Cys Ser Val Gly His Gln
5 10 15
gat atg tgt cgg tgaagcacgl: gatgctccag gaccctctga accacgacgt 157
Asp Met Cys Arg
CA 02361534 2002-02-22
150
<210> 370
<211> 22
<212> PRT
<213> Conus omaria
<400> 370
Leu Thr Val Arg Glu Glu Cys Cys Ser Asp Pro Arg Cys Ser Val Gly
1 5 10 15
His Gln Asp Met Cys Arg
<210> 371
<211> 151
<212> DNA
<213> Conus purpurascens
<220>
<221> CDS
<222> (1)..(120)
<400> 371
act gat ggc agg aat get gca gcc ata gcg ctt gac ctg atc get ccg 48
Thr Asp Gly Arg Asn Ala Ala Ala Ile Ala Leu Asp Leu Ile Ala Pro
1 5 10 15
gcc gtc agg gga gga tgc tgt tcc aat cct gcc tgt tta gtg aat cat 96
Ala Val Arg Gly Gly Cys Cys Ser Asn Pro Ala Cys Leu Val Asn His
20 25 30
cta gaa atg tgt ggt aaa aga cgc tgatgcccca ggaccctctg aaccacgacg 150
Leu Glu Met Cys Gly Lys Arg Arg
35 40
t 151
<210> 372
<211> 40
<212> PRT
<213> Conus purpurascens
<400> 372
Thr Asp Gly Arg Asn Ala Ala Ala Ile Ala Levu Asp Leu Ile Ala Pro
1 5 10 15
Ala Val Arg Gly Gly Cys Cys Ser Asn Pro Ala Cys Leu Val Asn His
20 25 30
Leu Glu Met Cys Gly Lys Arg Arg
35 40
<210> 373
CA 02361534 2002-02-22
151
<211> 160
<212> DNA
<213> Conus purpurascens
<220>
<221> CDS
<222> (1)..(120)
<400> 373
tct gat ggc agg gat gcc gca gcc aac gac aaa gcg tct gac ctg atc 48
Ser Asp Gly Arg Asp Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Ile
1 5 10 15
get ctg acc gcc agg aga gat cca tgc tgt ttc aat cct gcc tgt aac 96
Ala Leu Thr Ala Arg Arg Asp Pro Cys Cys Phe Asn Pro Ala Cys Asn
20 25 30
gtg aat aat cca cag att tat, ggt tgaagacgct gatgctccag gaccctctga 150
Val Asn Asn Pro Gln Ile Cys Gly
35 40
accacgacgt 160
<210> 374
<211> 40
<212> PRT
<213> Conus purpurascens
<400> 374
Ser Asp Gly Arg Asp Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Ile
1 5 10 15
Ala Leu Thr Ala Arg Arg Asp Pro Cys Cys Phe Asn Pro Ala Cys Asn
20 25 30
Val Asn Asn Pro Gln Ile Cys Gly
35 40
<210> 375
<211> 151
<212> DNA
<213> Conus purpurascens
<220>
<221> CDS
<222> (1)..(120)
<400> 375
tct gat ggc agg gat get gag aaa aca ggc ttt gac acg acc att gtg 48
Ser Asp Gly Arg Asp Ala Glu Lys Thr Gly Phe Asp Thr Thr Ile Val
1 5 10 15
CA 02361534 2002-02-22
152
ccg gaa gac tgc tgt tcg gat cct tcc tgt tgg agg ctg cat agt tta 96
Pro Glu Asp Cys Cys Ser Asp Pro Ser Cys Trp Arg Leu His Ser Leu
20 25 30
get tgt act gga att gta aac cgc tgatgctcca ggaccctctg aaccacgacg 150
Ala Cys Thr Gly Ile Val Asn Arg
35 40
t 151
<210> 376
<211> 40
<212> PRT
<213> Conus purpurascens
<400> 376
Ser Asp Gly Arg Asp Ala Glu Lys Thr Gly Phe Asp Thr Thr Ile Val
1 5 10 15
Pro Glu Asp Cys Cys Ser Asp Pro Ser Cys Trp Arg Leu His Ser Leu
20 25 30
Ala Cys Thr Gly Ile Val Asn Arg
35 40
<210> 377
<211> 142
<212> DNA
<213> Conus purpurascens
<220>
<221> CDS
<222> (1)..(111)
<400> 377
act gat ggc agg agt get gca gcc ata gcg ttt gcc ctg atc get ccg 48
Thr Asp Gly Arg Ser Ala Ala Ala Ile Ala Phe Ala Leu Ile Ala Pro
1 5 10 15
acc gtc tgc tgt act aat cct gcc tgt ctc gtg aat aat ata cgc ttt 96
Thr Val Cys Cys Thr Asn Pro Ala Cys Leu Val Asn Asn Ile Arg Phe
20 25 30
tgt ggt gga aga cgc tgatgcccca ggaccctctg aaccacgacg t 142
Cys Gly Gly Arg Arg
<210> 378
<211> 37
<212> PRT
CA 02361534 2002-02-22
153
<213> Conus purpurascens
<400> 378
Thr Asp Gly Arg Ser Ala Ala Ala Ile Ala Phe Ala Leu Ile Ala Pro
1 5 10 15
Thr Val Cys Cys Thr Asn Pro Ala Cys Leu Val Asn Asn Ile Arg Phe
20 25 30
Cys Gly Gly Arg Arg
<210> 379
<211> 157
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1)..(117)
<400> 379
tct gat gga aga aat gcc gca agc gac gcc aaa gcg ttt ccc cgg atc 48
Ser Asp Gly Arg Asn Ala Ala Ser Asp Ala Lys Ala Phe Pro Arg Ile
1 5 10 15
get cca atc gtc agg gac gaa tgc tgt agc gat cct agg tgt cac ggg 96
Ala Pro Ile Val Arg Asp Glu Cys Cys Ser Asp Pro Arg Cys His Gly
20 25 30
aat aat cgg gac cac tgt get tgaagacgct gctgctccag gaccctctga 147
Asn Asn Arg Asp His Cys Ala
accacgacgt 157
<210> 380
<211> 39
<212> PRT
<213> Conus regius
<400> 380
Ser Asp Gly Arg Asn Ala Ala Ser Asp Ala Lys Ala Phe Pro Arg Ile
1 5 10 15
Ala Pro Ile Val Arg Asp Glu Cys Cys Ser Asp Pro Arg Cys His Gly
20 25 30
Asn Asn Arg Asp His Cys Ala
<210> 381
CA 02361534 2002-02-22
:54
<211> 156
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1)..(117)
<400> 381
tct gat ggc agg aat acc gcg gcc gac gaa aaa gcg tcc gac ctg atc 48
Ser Asp Gly Arg Asn Thr Ala Ala Asp Glu Lys Ala Ser Asp Leu Ile
1 5 10 15
tct caa act gtc aag aga gat tgc tgt tcc cat cct ctc tgt aga tta 96
Ser Gln Thr Val Lys Arg Asp Cys Cys Ser His Pro Leu Cys Arg Leu
20 25 30
ttt gtt cca gga ctt tgt att tgaagacgct gctgctccag gaccctctga 147
Phe Val Pro Gly Leu Cys Ile
accacgact 156
<210> 382
<211> 39
<212> PRT
<213> Conus regius
<400> 382
Ser Asp Gly Arg Asn Thr Ala Ala Asp Glu Lys Ala Ser Asp Leu Ile
1 5 10 15
Ser Gln Thr Val Lys Arg Asp Cys Cys Ser His Pro Leu Cys Arg Leu
20 25 30
Phe Val Pro Gly Leu Cys Ile
<210> 383
<211> 157
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1).. (117)
<400> 383
tct gat ggc agg aat gcc gca gcc gac aac aaa gcg tct gac cta atc 48
Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Lys Ala Ser Asp Leu Ile
1 5 10 15
get caa atc gtc agg aga gga tgc tgt tcc cat cct gtc tgt aaa gtg 96
Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Val Cys Lys Val
20 25 30
CA 02361534 2002-02-22
155
agg tat cca gac ctg tgt cgt tgaagacgct gctgctccag gaccctctga 147
Arg Tyr Pro Asp Leu Cys Arg
accacgacgt 157
<210> 384
<211> 39
<212> PRT
<213> Conus regius
<400> 384
Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Lys Ala Ser Asp Leu Ile
1 5 10 15
Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Val Cys Lys Val
20 25 30
Arg Tyr Pro Asp Leu Cys Arg
<210> 385
<211> 157
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1)..(117)
<400> 385
tct gat ggc agg aat gcc gca gcc gac aac aga gcg tct gac cta atc 48
Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Arg Ala Ser Asp Leu Ile
1 5 10 15
get caa atc gtc agg aga gga tgc tgt tcc cat cct gcc tgt aat gtg 96
Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Ala Cys Asn Val
20 25 30
aat aat cca cac att tgt ggt tgaagacgct gctgctccag gaccctctga 147
Asn Asn Pro His Ile Cys Gly
accacgacgt 157
<210> 386
<211> 39
<212> PRT
<213> Conus regius
CA 02361534 2002-02-22
156
<400> 386
Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Arg Ala Ser Asp Leu Ile
1 5 10 15
Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Ala Cys Asn Val
20 25 30
Asn Asn Pro His Ile Cys Gly
<210> 387
<211> 157
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1)..(117)
<400> 387
tct gat ggc agg aat gcc gca gcc gac aac aaa ccg tct gac cta atc 48
Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Lys Pro Ser Asp Leu Ile
1 5 10 15
get caa atc gtc agg aga gga tgc tgt tcg cat cct gtc tgt aaa gtg 96
Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Val Cys Lys Val
20 25 30
agg tat tca gac atg tgt ggt tgaagacgct gctgctccag gaccctctga 147
Arg Tyr Ser Asp Met Cys Gly
accacgacgt 157
<210> 388
<211> 39
<212> PRT
<213> Conus regius
<400> 388
Ser Asp Gly Arg Asn Ala Ala Ala Asp Asn Lys Pro Ser Asp Leu Ile
1 5 10 15
Ala Gln Ile Val Arg Arg Gly Cys Cys Ser His Pro Val Cys Lys Val
20 25 30
Arg Tyr Ser Asp Met Cys Gly
<210> 389
<211> 154
<212> DNA
CA 02361534 2002-02-22
157
<213> Conus stercusmuscarum
<220>
<221> CDS
<222> (1)..(114)
<400> 389
tct gat ggc agg aat gca gag cga cga caa agc gtc tgt cct ggt cgc 48
Ser Asp Gly Arg Asn Ala Glu Arg Arg Gln Ser Val Cys Pro Gly Arg
1 5 10 15
tct ggc ccc agg gga gga tgt tgt tcc cac cct gcc tgt aag gtg cat 96
Ser Gly Pro Arg Gly Gly Cys Cys Ser His Pro Ala Cys Lys Val His
20 25 30
ttt cca cac agt tgt ggt tcgacgacgct gatgctccag gaccctctga 144
Phe Pro His Ser Cys Gly
accacgacgt 154
<210> 390
<211> 38
<212> PRT
<213> Conus stercusmuscarum
<400> 390
Ser Asp Gly Arg Asn Ala Glu Arg Arg Gln Ser Val Cys Pro Gly Arg
1 5 10 15
Ser Gly Pro Arg Gly Gly Cys Cys Ser His Pro Ala Cys Lys Val His
20 25 30
Phe Pro His Ser Cys Gly
<210> 391
<211> 145
<212> DNA
<213> Conus stercusmuscarum
<220>
<221> CDS
<222> (1).,(114)
<400> 391
tct gat ggc agg aat gcc gca gcc agc gac aga gcg tct gac gcg gcc 48
Ser Asp Gly Arg Asn Ala Ala Ala Ser Asp Arg Ala Ser Asp Ala Ala
1 5 10 15
cac cag gta tgc tgt tcc aac cct gtc tgt cac gtg gat cat cca gaa 96
His Gin Val Cys Cys Ser Asn Pro Val Cys His Val Asp His Pro Glu
20 25 30
CA 02361534 2002-02-22
158
ctt tgt cgt aga aga cgc tgatgctcca ggaccctctg aaccacgacg t 145
Leu Cys Arg Arg Arg Arg
<210> 392
<211> 38
<212> PRT
<213> Conus stercusmuscarum
<400> 392
Ser Asp Gly Arg Asn Ala Ala Ala Ser Asp Arg Ala Ser Asp Ala Ala
1 5 10 15
His Gln Val Cys Cys Ser Asn Pro Val Cys His Val Asp His Pro Glu
20 25 30
Leu Cys Arg Arg Arg Arg
<210> 393
<211> 154
<212> DNA
<213> Conus striatus
<220>
<221> CDS
<222> (1)..(123)
<400> 393
tct gat ggc agg aat gcc gcg gcc aac gac aaa gcg tct gac ctg gtc 48
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Val
1 5 10 15
get ccg gcc atc agg gga tgc tgt tcc cac cct gtc tgt aac ttg agt 96
Ala Pro Ala Ile Arg Gly Cys Cys Ser His Pro Val Cys Asn Leu Ser
20 25 30
aat cca caa att tgt cgt gga aga cgc tgatgctcca ggaccctctg 143
Asn Pro Gln Ile Cys Arg Gly Arg Arg
35 40
aaccacgacg t 154
<210> 394
<211> 41
<212> PRT
<213> Conus striatus
<400> 394
Ser Asp Gly Arg Asn Ala Ala Ala Asn Asp Lys Ala Ser Asp Leu Val
1 5 10 15
CA 02361534 2002-02-22
159
Ala Pro Ala Ile Arg Gly Cys Cys Ser His Pro Val Cys Asn Leu Ser
20 25 30
Asn Pro Gln Ile Cys Arg Gly Arg Arg
35 40
<210> 395
<211> 117
<212> DNA
<213> Conus textile
<220>
<221> CDS
<222> (1)..(114)
<400> 395
ttt cat ggc agg aat gcc gca gcc aaa gcg tct ggc ctg gtc ggt ctg 48
Phe His Gly Arg Asn Ala Ala Ala Lys Ala Ser Gly Leu Val Gly Leu
1 5 10 15
acc gac aag agg caa gaa tgc tgt tct cat cct gcc tgt aac gta gat 96
Thr Asp Lys Arg Gln Glu Cys Cys Ser His Pro Ala Cys Asn Val Asp
20 25 30
cat cca gaa att tgt cgt tga 117
His Pro Glu Ile Cys Arg
<210> 396
<211> 38
<212> PRT
<213> Conus textile
<400> 396
Phe His Gly Arg Asn Ala Ala Ala Lys Ala Ser Gly Leu Val Gly Leu
1 5 10 15
Thr Asp Lys Arg Gln Glu Cys Cys Ser His Pro Ala Cys Asn Val Asp
20 25 30
His Pro Glu Ile Cys Arg
<210> 397
<211> 151
<212> DNA
<213> Conus tulipa
<220>
<221> CDS
<222> (1) .. (120)
<400> 397
CA 02361534 2002-02-22
X60
act gat ggc agg agt get gca gcc ata gcg ttt gcc ctg atc get ccg 48
Thr Asp Gly Arg Ser Ala Ala Ala Ile Ala Phe Ala Leu Ile Ala Pro
1 5 10 15
acc gtc tgg gaa gga tgc tgt tct aat cct gcc tgt ctc gtg aat cat 96
Thr Val Trp Glu Gly Cys Cys Ser Asn Pro Ala Cys Leu Val Asn His
20 25 30
ata cgc ttt tgt ggt gga aga cgc tgatgcccca ggaccctctg aaccacgacg 150
Ile Arg Phe Cys Gly Gly Arg Arg
35 40
t 151
<210> 398
<211> 40
<212> PRT
<213> Conus tulipa
<400> 398
Thr Asp Gly Arg Ser Ala Ala Ala Ile Ala Phe Ala Leu Ile Ala Pro
1 5 10 15
Thr Val Trp Glu Gly Cys Cys Ser Asn Pro Ala Cys Leu Val Asn His
20 25 30
Ile Arg Phe Cys Gly Gly Arg Arg
35 40
<210> 399
<211> 157
<212> DNA
<213> Conus virgo
<220>
<221> CDS
<222> (1)..(117)
<400> 399
tct aat ggc atg aat gcc gca gcc atc agg aaa gcg tct gcc ctg gtg 48
Ser Asn Gly Met Asn Ala Ala Ala Ile Arg Lys Ala Ser Ala Leu Val
1 5 10 15
get cag atc gcc cat cga gac tgc tgt gac gat cct gcc tgc acc gtg 96
Ala Gln Ile Ala His Arg Asp Cys Cys Asp Asp Pro Ala Cys Thr Val
20 25 30
aat aat cca ggc ctt tgc act tgaagatgct gctgccccag gaccctctga 147
Asn Asn Pro Gly Leu Cys Thr
accacgacgt 157
CA 02361534 2002-02-22
161
<210> 400
<211> 39
<212> PRT
<213> Conus virgo
<400> 400
Ser Asn Gly Met Asn Ala Ala Ala Ile Arg Lys Ala Ser Ala Leu Val
1 5 10 15
Ala Gln Ile Ala His Arg Asp Cys Cys Asp Asp Pro Ala Cys Thr Val
20 25 30
Asn Asn Pro Gly Leu Cys Thr
<210> 401
<211> 154
<212> DNA
<213> Conus geographus
<220>
<221> CDS
<222> (1)..(114)
<400> 401
tct gat ggc ggg aat gcc gca gca aaa gag tct gac gtg atc get ctg 48
Ser Asp Gly Gly Asn Ala Ala Ala Lys Glu Ser Asp Val Ile Ala Leu
1 5 1.0 15
acc gtc tgg aaa tgc tgt acc att cct tcc tgt tat gag aaa aaa aaa 96
Thr Val Trp Lys Cys Cys Thr Ile Pro Ser C'ys Tyr Glu Lys Lys Lys
20 25 30
att aaa gca tgt gtc ttt tgacgacgct gatgctccag gaccctctga 144
Ile Lys Ala Cys Val Phe
accacgacgt 154
<210> 402
<211> 38
<212> PRT
<213> Conus geographus
<400> 402
Ser Asp Gly Gly Asn Ala. Ala Ala Lys Glu Ser Asp Val Ile Ala Leu
1 5 10 15
Thr Val Trp Lys Cys Cys Thr Ile Pro Ser Cys Tyr Glu Lys Lys Lys
20 25 30
Ile Lys Ala Cys Val Phe
CA 02361534 2002-02-22
X62
<210> 403
<211> 154
<212> DNA
<213> Conus regius
<220>
<221> CDS
<222> (1)..(114)
<400> 403
tct gat ggc gca gtc gac gac aaa gcg ttg gat cga atc get gaa atc 48
Ser Asp Gly Ala Val Asp Asp Lys Ala Leu Asp Arg Ile Ala Glu Ile
1 5 10 15
gtc agg aga gga tgc tgt ggc aat cct gcc tgt agc ggc tcc tcg aaa 96
Val Arg Arg Gly Cys Cys Gly Asn Pro Ala Cys Ser Gly Ser Ser Lys
20 25 30
gat gca ccc tct tgt ggt tgaagacgat gctgctccag gaccctctga 144
Asp Ala Pro Ser Cys Gly
accacgacgt 154
<210> 404
<211> 38
<212> PRT
<213> Conus regius
<400> 404
Ser Asp Gly Ala Val Asp Asp Lys Ala Leu Asp Arg Ile Ala Glu Ile
1 5 1.0 15
Val Arg Arg Gly Cys Cys Gly Asn Pro Ala Cys Ser Gly Ser Ser Lys
20 25 30
Asp Ala Pro Ser Cys Gly
