CA2361534A1 - Alpha-conotoxin peptides - Google Patents
Alpha-conotoxin peptides Download PDFInfo
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- CA2361534A1 CA2361534A1 CA002361534A CA2361534A CA2361534A1 CA 2361534 A1 CA2361534 A1 CA 2361534A1 CA 002361534 A CA002361534 A CA 002361534A CA 2361534 A CA2361534 A CA 2361534A CA 2361534 A1 CA2361534 A1 CA 2361534A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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Abstract
The invention relates to relatively short peptides (termed .alpha. -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.
Claims (39)
1. A substantially pure .alpha.-conotoxin peptide having the generic formula I: Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Cys-Cys-Xaa6-Xaa7-Xaa8-Xaa9-Cys-Xaa10-Xaa11-Xaa12-Cys-Xaa13 (SEQ ID
NO1:), wherein Xaa1 is des-Xaa1, 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-Xaa4, Asp, Phe, Gly, Ala, Glu,.gamma.-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, O-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; Xaa11 is Gln, Leu, His, halo-His, Trp (D or L), halo-Trp, neo-Trp, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-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-Xaa13, 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; and the C-terminus contains a free carboxyl group or an amide group.
NO1:), wherein Xaa1 is des-Xaa1, 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-Xaa4, Asp, Phe, Gly, Ala, Glu,.gamma.-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, O-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; Xaa11 is Gln, Leu, His, halo-His, Trp (D or L), halo-Trp, neo-Trp, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-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-Xaa13, 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; and the C-terminus contains a free carboxyl group or an amide group.
2. A substantially pure .alpha.-conotoxin peptide of generic formula I
selected from the group consisting of:
Asp-Xaa1-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-Xaa1-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 Xaa1 is Glu or .gamma.-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, or derivatives thereof.
selected from the group consisting of:
Asp-Xaa1-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-Xaa1-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 Xaa1 is Glu or .gamma.-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, or derivatives thereof.
3. The substanially pure .alpha.-conotoxin peptide of claim 2, wherein Xaa1 is Glu.
4. The substantially pure .alpha.-conotoxin peptide of claim 2, wherein Xaa2 is Lys.
5. The substantially pure .alpha.-conotoxin peptide of claim 2, wherein Xaa4 is Tyr.
6. The substantially pure .alpha.-conotoxin peptide of claim 2, wherein Xaa4 is mono-iodo-Tyr.
7. The substantially pure .alpha.-conotoxin peptide of claim 2, wherein Xaa4 is di-iodo-Tyr.
8. The substantially pure .alpha.-conotoxin peptide of claim 1, which is modified to contain an O-glycan, an S-glycan or an N-glycan.
9. The substantially pure .alpha.-conotoxin peptide of claim 2 which is modified to contain an O-glycan, an S-glycan or an N-glycan.
10. A substantially pure .alpha.-conotoxin peptide having the generic formula II: Xaa1-Xaa2-Xaa3-Xaa4-Cys-Cys-Xaa5-Xaa6-Xaa7 Xaa8-Cys-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Cys-Xaa15-Xaa16-Xaa17 (SEQ ID NO:2), wherein Xaa1 is des-Xaa1, Asp, Glu or .gamma.-carboxy-Glu (Gla);
Xaa2 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, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa6 is Asp, Asn, His, halo-His, Thr, Ser, 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 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, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid;
Xaa9 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, 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; Xaa11 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, O-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, O-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, O-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, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; and Xaa15 is des-Xaa15, Gly, Ala, Met, Ser, Thr, 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; 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; and the C-terminus contains a free carboxyl group or an amide group.
Xaa2 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, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; Xaa6 is Asp, Asn, His, halo-His, Thr, Ser, 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 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, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid;
Xaa9 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, 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; Xaa11 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, O-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, O-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, O-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, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid; and Xaa15 is des-Xaa15, Gly, Ala, Met, Ser, Thr, 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; 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; and the C-terminus contains a free carboxyl group or an amide group.
11. A substantially pure .alpha.-conotoxin peptide of generic formula II
seleceted from the group consisting of:
Cys-Cys-Ser-Asp-Xaa5-Ala-Cys-Xaa2-Gln-Thr-Xaa5-Gly-Cys-Arg (SEQ ID NO:13);
Cys-Cys-Xaa1-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-Xaa1-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-Xaa2-Xaa4-Xaa4-Cys-Xaa3-Xaa2 (SEQ
ID NO:154);
Xaa6-Xaa1-Xaa5-Gly-Cys-Cys-Arg-His-Xaa5-Ala-Cys-Gly-Xaa2-Asn-Arg-Cys (SEQ
ID NO:155);
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-Xaa2-Thr-Xaa4-Cys-Ser-Xaa3-Xaa2 (SEQ ID NO:157);
Cys-Cys-Ser-Asn-Xaa5-Thr-Cys-Xaa2-Xaa1-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-Xaa1-Thr-Xaa4-Gly-Cys (SEQ ID NO:160);
Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Xaa2-Xaa1-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 Xaa1 is Glu or .gamma.-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, or derivatives thereof.
seleceted from the group consisting of:
Cys-Cys-Ser-Asp-Xaa5-Ala-Cys-Xaa2-Gln-Thr-Xaa5-Gly-Cys-Arg (SEQ ID NO:13);
Cys-Cys-Xaa1-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-Xaa1-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-Xaa2-Xaa4-Xaa4-Cys-Xaa3-Xaa2 (SEQ
ID NO:154);
Xaa6-Xaa1-Xaa5-Gly-Cys-Cys-Arg-His-Xaa5-Ala-Cys-Gly-Xaa2-Asn-Arg-Cys (SEQ
ID NO:155);
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-Xaa2-Thr-Xaa4-Cys-Ser-Xaa3-Xaa2 (SEQ ID NO:157);
Cys-Cys-Ser-Asn-Xaa5-Thr-Cys-Xaa2-Xaa1-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-Xaa1-Thr-Xaa4-Gly-Cys (SEQ ID NO:160);
Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Xaa2-Xaa1-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 Xaa1 is Glu or .gamma.-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, or derivatives thereof.
12. The substantially pure .alpha.-conotoxin peptide of claim 11, wherein Xaa2 is Lys.
13. The substantially pure .alpha.-conotoxin peptide of claim 11, wherein Xaa1 is Glu.
14. The substantially pure .alpha.-conotoxin peptide of claim 11, wherein Xaa3 is Trp.
15. The substantially pure .alpha.-conotoxin peptide of claim 11, wherein Xaa4 is Tyr.
16. The substantially pure .alpha.-conotoxin peptide of claim 11, wherein Xaa4 is mono-iodo-Tyr.
17. The substantially pure .alpha.-conotoxin peptide of claim 11, wherein Xaa4 is di-iodo-Tyr.
18. The substantially pure .alpha.-conotoxin peptide of claim 10, which is modified to contain an O-glycan, an S-glycan or an N-glycan.
19 The substantially pure .alpha.-conotoxin peptide of claim 11 which is modified to contain an O-glycan, an S-glycan or an N-glycan.
20. A substantially pure .alpha.-conotoxin peptide having the generic formula III: Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Cys-Cys-Xaa6-Xaa7-Xaa8-Xaa9-Cys-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-Cys-Xaa17-Xaa18-Xaa19-Xaa20-Xaa21,-Xaa22-Xaa23-Xaa24 (SEQ ID NO:3), wherein Xaa is des-Xaa1, Ser or Thr; Xaa2 is des-Xaa2, Asp, Glu, .UPSILON.-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, Gln, 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, 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, O-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-His, any unnatural aromatic amino acid, Leu, Met, Gly, Ala, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-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, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid;
Xaa14 is Ser, Thr, Ala, Gln, 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, O-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, O-phospho-Tyr, nitro-Tyr, any unnatural hydroxy containing amino acid, Glu, Gla, Ala, 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;
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; Xaa18 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, ornithine, 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-Xaa21, 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; and the C-terminus contains a free carboxyl group or an amide group, 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, Xaa21, is des-Xaa21, Xaa22 is des-Xaa22, Xaa23 is des-Xaa23, and Xaa24 is des-Xaa24.
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, Gln, 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, 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, O-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-His, any unnatural aromatic amino acid, Leu, Met, Gly, Ala, Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-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, O-phospho-Tyr, nitro-Tyr or any unnatural hydroxy containing amino acid;
Xaa14 is Ser, Thr, Ala, Gln, 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, O-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, O-phospho-Tyr, nitro-Tyr, any unnatural hydroxy containing amino acid, Glu, Gla, Ala, 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;
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; Xaa18 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, ornithine, 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-Xaa21, 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; and the C-terminus contains a free carboxyl group or an amide group, 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, Xaa21, is des-Xaa21, Xaa22 is des-Xaa22, Xaa23 is des-Xaa23, and Xaa24 is des-Xaa24.
21. A substantially pure .alpha.-conotoxin peptide of generic forumula III
selected from the group consisting of:
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Ser-Asn-Met-Cys (SEQ ID
NO:22);
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Arg-Gln-Asn-Asn-Ala-Xaa1-Xaa4-Cys-Arg (SEQ ID NO:23);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-Arg (SEQ ID NO:24);
Xaa5-Xaa1-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-Arg (SEQ ID NO:25);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-Asp (SEQ ID NO:26);
Xaa5-Arg-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-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-Xaa1-Thr-Cys-Arg (SEQ ID NO:29);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Val-Cys-Arg (SEQ ID NO:30);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Ile-Asp-His-Xaa5-Xaa1-Ile-Cys-Arg (SEQ ID NO:31);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-Arg-Arg-Arg-Arg (SEQ ID NO:32);
Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Val-Asn-His-Xaa5-Xaa1-Leu-Cys (SEQ ID NO:33);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Asn-His-Xaa5-Xaa1-Leu-Cys(SEQ ID
NO:34);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys(SEQ ID
NO:35);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Xaa2-Thr-Gln-Xaa1-Xaa5-Cys-Arg-Xaa1-Ser (SEQ ID NO:36);
Xaa5-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Xaa5-Xaa1-Phe-Cys-Arg-Gln (SEQ ID NO:37);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Xaa5-Xaa1-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 ID
NO:44);
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Val-Xaa1-His-Xaa5-Xaa1-Leu-Cys-Arg-Arg-Arg-Arg (SEQ ID NO:45);
Gly-Gly-Cys-Cys-Ser-Phe-Xaa5-Ala-Cys-Arg-Xaa2-Xaa5-Arg-Xaa5-Xaa1-Met-Cys-Gly (SEQ ID NO:46);
Xaa5-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Ser-Ser-His-Xaa5-Xaa1-Leu-Cys-Gly (SEQ ID NO:47);
Xaa5-Gln-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Val-Gly-His-Xaa5-Xaa1-Leu-Cys-Gly (SEQ ID NO:48);
Xaa6-Val-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Val-Gly-His-Xaa5-Xaa1-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);
Xaa5-Gln-Cys-Cys-Ser-His-Leu-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-Arg (SEQ ID NO:51);
Gly-Cys-Cys-Ser-Xaa4-Phe-Asp-Cys-Arg-Met-Met-Phe-Xaa5-Xaa1-Met-Cys-Gly-Xaa3-Arg (SEQ ID NO:52);
Gly-Gly-Cys-Cys-Ser-Phe-Ala-Ala-Cys-Arg-Xaa2-Xaa4-Arg-Xaa5-Xaa1-Met-Cys-Gly (SEQ ID NO:53);
Gly-Gly-Cys-Cys-Phe-His-Xaa5-Val-Cys-Xaa4-Ile-Asn-Leu-Leu-Xaa1-Met-Cys-Arg-Gln-Arg (SEQ ID NO:54);
Ser-Ala-Thr-Cys-Cys-Asn-Xaa4-Xaa5-Xaa5-Cys-Xaa4-Xaa1-Thr-Xaa4-Xaa5-Xaa1-Ser-Cys-Leu (SEQ ID NO:55);
Ala-Cys-Cys-Ala-Xaa4-Xaa5-Xaa5-Cys-Phe-Xaa1-Ala-Xaa4-Xaa5-Xaa1-Arg-Cys-Leu (SEQ ID NO:56);
Asn-Ala-Xaa1-Cys-Cys-Xaa4-Xaa4-Xaa5-Xaa5-Cys-Xaa4-Xaa1-Ala-Xaa4-Xaa5-Xaa1-Ile-Cys-Leu (SEQ ID NO:57);
Xaa1-Cys-Cys-Thr-Asn-Xaa5-Val-Cys-His-Ala-Xaa1-His-Gln-Xaa1-Leu-Cys-Ala-Arg-Arg-Arg (SEQ ID NO:170);
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Ser-Asn-Leu-Cys (SEQ ID
NO:171);
Xaa1-Cys-Cys-Thr-Asn-Xaa5-Val-Cys-His-Val-Xaa1-His-Gln-Xaa1-Leu-Cys-Ala-Arg-Arg-Arg (SEQ ID NO:172);
Xaa6-Xaa1-Cys-Cys-Ser-Xaa4-Xaa5-Ala-Cys-Asn-Leu-Asp-His-Xaa5-Xaa1-Leu-Cys (SEQ ID NO:173);
Xaa5-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Ser-Thr-His-Xaa5-Xaa1-Leu-Cys-Gly (SEQ ID NO:174);
Leu-Asn-Cys-Cys-Met-Ile-Xaa5-Xaa5-Cys-Xaa3-Xaa2-Xaa2-Xaa4-Gly-Asp-Arg-Cys-Ser-Xaa1-Val-Arg (SEQ ID NO:175);
Ala-Phe-Gly-Cys-Cys-Asp-Leu-Ile-Xaa5-Cys-Leu-Xaa1-Arg-Xaa4-Gly-Asn-Arg-Cys-Asn-Xaa1-Val-His (SEQ ID NO:176);
Leu-Gly-Cys-Cys-Asn-Val-Thr-Xaa5-Cys-Xaa3-Xaa1-Xaa2-Xaa4-Gly-Asp-Xaa2-Cys-Asn-Xaa1-Val-Arg (SEQ ID NO:177);
Asp-Xaa1-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Arg-Val-Asn-Asn-Xaa5-His-Val-Cys-Arg-Arg-Arg (SEQ ID NO:178);
Leu-Asn-Cys-Cys-Ser-Ile-Xaa5-Gly-Cys-Xaa3-Asn-Xaa1-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-Xaa1-Leu-Cys(SEQ
ID NO:183);
Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Ala-Cys-Ser-Val-Xaa1-His-Gln-Asp-Leu-Cys-Asp (SEQ ID NO:184);
Val-Ser-Cys-Cys-Val-Val-Arg-Xaa5-Cys-Xaa3-Ile-Arg-Xaa4-Gln-Xaa1-Xaa1-Cys-Leu-Xaa1-Ala-Asp-Xaa5-Arg-Thr-Leu (SEQ ID NO:185);
Xaa6-Asn-Cys-Cys-Ser-Ile-Xaa5-Gly-Cys-Xaa3-Xaa1-Xaa2-Xaa4-Gly-Asp-Xaa2-Cys-Ser-Xaa1-Val-Arg (SEQ ID NO:186);
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-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);
Xaa1-Cys-Cys-Ser-Gln-Xaa5-Xaa5-Cys-Arg-Xaa3-Xaa2-His-Xaa5-Xaa1-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);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa5-His-Ile-Cys (SEQ ID
NO:192);
Thr-Xaa5-Xaa1-Xaa1-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);
Xaa1-Asp-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-Asp-Leu-Cys(SEQ
ID NO:195);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Ser-Asn-Ala-His-Ile-Cys (SEQ ID
NO:196);
Xaa1-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 ID
NO:198);
Gly-Cys-Cys-Gly-Asn-Xaa5-Ser-Cys-Ser-Ile-His-Ile-Xaa5-Xaa4-Val-Cys-Asn (SEQ
ID NO:199);
Thr-Asp-Ser-Xaa1-Xaa1-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 NO:201);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Asn-Asn-Xaa5-Asp-Ile-Cys (SEQ ID
NO:202);
Gly-Xaa2-Cys-Cys-Ile-Asn-Asp-Ala-Cys-Arg-Ser-Xaa2-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 NO:204);
Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Arg-Phe-Asn-Xaa4-Xaa5-Xaa2-Xaa4-Cys-Gly (SEQ ID NO:205);
Asp-Xaa1-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-Xaa1-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-Xaa1-Xaa4-Cys-Arg-Xaa1-Ser (SEQ ID NO:209);
Asp-Xaa5-Cys-Cys-Ser-Xaa4-Xaa5-Asp-Cys-Gly-Ala-Asn-His-Xaa5-Xaa1-Ile-Cys-Gly (SEQ ID NO:210);
Xaa1-Cys-Cys-Ser-Gln-Xaa5-Xaa5-Cys-Arg-Xaa3-Xaa2 His-Xaa5-Xaa1-Leu-Cys-Ser (SEQ ID NO:211);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Ile-Cys (SEQ ID
NO:212);
Gly-Cys-Cys-Ser-Asp-Xaa5-Ser-Cys-Asn-Val-Asn-Asn-Xaa5-Asp-Xaa4-Cys (SEQ
ID NO:213);
Xaa1-Xaa1-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-Xaa1-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 (SEQ ID
NO:218);
Asp-Xaa1-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 (SEQ ID
NO: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);
Val-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Val-Asp-His-Xaa5-Xaa1-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-Xaa1-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-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), wherein Xaa1 is Glu or .gamma.-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, or derivatives thereof.
selected from the group consisting of:
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Ser-Asn-Met-Cys (SEQ ID
NO:22);
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Arg-Gln-Asn-Asn-Ala-Xaa1-Xaa4-Cys-Arg (SEQ ID NO:23);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-Arg (SEQ ID NO:24);
Xaa5-Xaa1-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-Arg (SEQ ID NO:25);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-Asp (SEQ ID NO:26);
Xaa5-Arg-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-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-Xaa1-Thr-Cys-Arg (SEQ ID NO:29);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Val-Cys-Arg (SEQ ID NO:30);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Ile-Asp-His-Xaa5-Xaa1-Ile-Cys-Arg (SEQ ID NO:31);
Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-Arg-Arg-Arg-Arg (SEQ ID NO:32);
Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Val-Asn-His-Xaa5-Xaa1-Leu-Cys (SEQ ID NO:33);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Asn-His-Xaa5-Xaa1-Leu-Cys(SEQ ID
NO:34);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys(SEQ ID
NO:35);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Xaa2-Thr-Gln-Xaa1-Xaa5-Cys-Arg-Xaa1-Ser (SEQ ID NO:36);
Xaa5-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Xaa5-Xaa1-Phe-Cys-Arg-Gln (SEQ ID NO:37);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Xaa5-Xaa1-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 ID
NO:44);
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Val-Xaa1-His-Xaa5-Xaa1-Leu-Cys-Arg-Arg-Arg-Arg (SEQ ID NO:45);
Gly-Gly-Cys-Cys-Ser-Phe-Xaa5-Ala-Cys-Arg-Xaa2-Xaa5-Arg-Xaa5-Xaa1-Met-Cys-Gly (SEQ ID NO:46);
Xaa5-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Ser-Ser-His-Xaa5-Xaa1-Leu-Cys-Gly (SEQ ID NO:47);
Xaa5-Gln-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Val-Gly-His-Xaa5-Xaa1-Leu-Cys-Gly (SEQ ID NO:48);
Xaa6-Val-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Val-Gly-His-Xaa5-Xaa1-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);
Xaa5-Gln-Cys-Cys-Ser-His-Leu-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-Arg (SEQ ID NO:51);
Gly-Cys-Cys-Ser-Xaa4-Phe-Asp-Cys-Arg-Met-Met-Phe-Xaa5-Xaa1-Met-Cys-Gly-Xaa3-Arg (SEQ ID NO:52);
Gly-Gly-Cys-Cys-Ser-Phe-Ala-Ala-Cys-Arg-Xaa2-Xaa4-Arg-Xaa5-Xaa1-Met-Cys-Gly (SEQ ID NO:53);
Gly-Gly-Cys-Cys-Phe-His-Xaa5-Val-Cys-Xaa4-Ile-Asn-Leu-Leu-Xaa1-Met-Cys-Arg-Gln-Arg (SEQ ID NO:54);
Ser-Ala-Thr-Cys-Cys-Asn-Xaa4-Xaa5-Xaa5-Cys-Xaa4-Xaa1-Thr-Xaa4-Xaa5-Xaa1-Ser-Cys-Leu (SEQ ID NO:55);
Ala-Cys-Cys-Ala-Xaa4-Xaa5-Xaa5-Cys-Phe-Xaa1-Ala-Xaa4-Xaa5-Xaa1-Arg-Cys-Leu (SEQ ID NO:56);
Asn-Ala-Xaa1-Cys-Cys-Xaa4-Xaa4-Xaa5-Xaa5-Cys-Xaa4-Xaa1-Ala-Xaa4-Xaa5-Xaa1-Ile-Cys-Leu (SEQ ID NO:57);
Xaa1-Cys-Cys-Thr-Asn-Xaa5-Val-Cys-His-Ala-Xaa1-His-Gln-Xaa1-Leu-Cys-Ala-Arg-Arg-Arg (SEQ ID NO:170);
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Ser-Asn-Leu-Cys (SEQ ID
NO:171);
Xaa1-Cys-Cys-Thr-Asn-Xaa5-Val-Cys-His-Val-Xaa1-His-Gln-Xaa1-Leu-Cys-Ala-Arg-Arg-Arg (SEQ ID NO:172);
Xaa6-Xaa1-Cys-Cys-Ser-Xaa4-Xaa5-Ala-Cys-Asn-Leu-Asp-His-Xaa5-Xaa1-Leu-Cys (SEQ ID NO:173);
Xaa5-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Ser-Thr-His-Xaa5-Xaa1-Leu-Cys-Gly (SEQ ID NO:174);
Leu-Asn-Cys-Cys-Met-Ile-Xaa5-Xaa5-Cys-Xaa3-Xaa2-Xaa2-Xaa4-Gly-Asp-Arg-Cys-Ser-Xaa1-Val-Arg (SEQ ID NO:175);
Ala-Phe-Gly-Cys-Cys-Asp-Leu-Ile-Xaa5-Cys-Leu-Xaa1-Arg-Xaa4-Gly-Asn-Arg-Cys-Asn-Xaa1-Val-His (SEQ ID NO:176);
Leu-Gly-Cys-Cys-Asn-Val-Thr-Xaa5-Cys-Xaa3-Xaa1-Xaa2-Xaa4-Gly-Asp-Xaa2-Cys-Asn-Xaa1-Val-Arg (SEQ ID NO:177);
Asp-Xaa1-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Arg-Val-Asn-Asn-Xaa5-His-Val-Cys-Arg-Arg-Arg (SEQ ID NO:178);
Leu-Asn-Cys-Cys-Ser-Ile-Xaa5-Gly-Cys-Xaa3-Asn-Xaa1-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-Xaa1-Leu-Cys(SEQ
ID NO:183);
Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Ala-Cys-Ser-Val-Xaa1-His-Gln-Asp-Leu-Cys-Asp (SEQ ID NO:184);
Val-Ser-Cys-Cys-Val-Val-Arg-Xaa5-Cys-Xaa3-Ile-Arg-Xaa4-Gln-Xaa1-Xaa1-Cys-Leu-Xaa1-Ala-Asp-Xaa5-Arg-Thr-Leu (SEQ ID NO:185);
Xaa6-Asn-Cys-Cys-Ser-Ile-Xaa5-Gly-Cys-Xaa3-Xaa1-Xaa2-Xaa4-Gly-Asp-Xaa2-Cys-Ser-Xaa1-Val-Arg (SEQ ID NO:186);
Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-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);
Xaa1-Cys-Cys-Ser-Gln-Xaa5-Xaa5-Cys-Arg-Xaa3-Xaa2-His-Xaa5-Xaa1-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);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa5-His-Ile-Cys (SEQ ID
NO:192);
Thr-Xaa5-Xaa1-Xaa1-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);
Xaa1-Asp-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-Asp-Leu-Cys(SEQ
ID NO:195);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Ser-Asn-Ala-His-Ile-Cys (SEQ ID
NO:196);
Xaa1-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 ID
NO:198);
Gly-Cys-Cys-Gly-Asn-Xaa5-Ser-Cys-Ser-Ile-His-Ile-Xaa5-Xaa4-Val-Cys-Asn (SEQ
ID NO:199);
Thr-Asp-Ser-Xaa1-Xaa1-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 NO:201);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Asn-Asn-Xaa5-Asp-Ile-Cys (SEQ ID
NO:202);
Gly-Xaa2-Cys-Cys-Ile-Asn-Asp-Ala-Cys-Arg-Ser-Xaa2-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 NO:204);
Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Arg-Phe-Asn-Xaa4-Xaa5-Xaa2-Xaa4-Cys-Gly (SEQ ID NO:205);
Asp-Xaa1-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-Xaa1-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-Xaa1-Xaa4-Cys-Arg-Xaa1-Ser (SEQ ID NO:209);
Asp-Xaa5-Cys-Cys-Ser-Xaa4-Xaa5-Asp-Cys-Gly-Ala-Asn-His-Xaa5-Xaa1-Ile-Cys-Gly (SEQ ID NO:210);
Xaa1-Cys-Cys-Ser-Gln-Xaa5-Xaa5-Cys-Arg-Xaa3-Xaa2 His-Xaa5-Xaa1-Leu-Cys-Ser (SEQ ID NO:211);
Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Ile-Cys (SEQ ID
NO:212);
Gly-Cys-Cys-Ser-Asp-Xaa5-Ser-Cys-Asn-Val-Asn-Asn-Xaa5-Asp-Xaa4-Cys (SEQ
ID NO:213);
Xaa1-Xaa1-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-Xaa1-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 (SEQ ID
NO:218);
Asp-Xaa1-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 (SEQ ID
NO: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);
Val-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Val-Asp-His-Xaa5-Xaa1-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-Xaa1-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-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), wherein Xaa1 is Glu or .gamma.-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, or derivatives thereof.
22. The substantially pure .alpha.-conotoxin peptide of claim 21, wherein Xaa2 is Lys.
23. The substantially pure .alpha.-conotoxin peptide of claim 21, wherein Xaa1 is Glu.
24. The substantially pure .alpha.-conotoxin peptide of claim 21, wherein Xaa3 is Trp.
25. The substantially pure .alpha.-conotoxin peptide of claim 21, wherein Xaa4 is Tyr.
26. The substantially pure .alpha.-conotoxin peptide of claim 21, wherein Xaa4 is mono-iodo-Tyr.
27. The substantially pure .alpha.-conotoxin peptide of claim 21, wherein Xaa4 is di-iodo-Tyr.
28. The substantially pure .alpha.-conotoxin peptide of claim 20, which is modified to contain an O-glycan, an S-glycan or an N-glycan.
29 The substantially pure .alpha.-conotoxin peptide of claim 21 which is modified to contain an O-glycan, an S-glycan or an N-glycan.
30. A substantially pure .alpha.-conotoxin peptide seleceted from the group consisting of:
Cys-Cys-Thr-Ile-Xaa5-Ser-Cys-Xaa4-Xaa1-Xaa2-Xaa2-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 Xaa1 is Glu or .gamma.-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, or derivatives thereof.
Cys-Cys-Thr-Ile-Xaa5-Ser-Cys-Xaa4-Xaa1-Xaa2-Xaa2-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 Xaa1 is Glu or .gamma.-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, or derivatives thereof.
31. The substantially pure .alpha.-conotoxin peptide of claim 30, wherein Xaa2 is Lys.
32. The substantially pure .alpha.-conotoxin peptide of claim 30, wherein Xaa1 is Glu.
33. The substantially pure .alpha.-conotoxin peptide of claim 30, wherein Xaa4 is Tyr.
34. The substantially pure .alpha.-conotoxin peptide of claim 30, wherein Xaa4 is mono-iodo-Tyr.
35. The substantially pure .alpha.-conotoxin peptide of claim 30, wherein Xaa4 is di-iodo-Tyr.
36. The substantially pure .alpha.-conotoxin peptide of claim 30, which is modified to contain an O-glycan, an S-glycan or an N-glycan.
37. An isolated nucleic acid comprising a nucleic acid coding for an .alpha.-conotoxin precursor comprising an amino acid sequence selected from the group of amino acid sequences set forth in Tables 1-134.
38. The nucleic acid of claim 37 wherein the nucleic acid comprises a nucleotide sequence selected from the group of nucleotide sequences set forth in Tables 1-134 or their complements.
39. A substantially pure .alpha.-conotoxin protein precursor comprising an amino acid sequence selected from the group of amino acid sequences set forth in Tables 1-134.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2743116A CA2743116C (en) | 1999-01-29 | 2000-01-28 | Alpha-conotoxin peptides with a 4/7 motif |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11838199P | 1999-01-29 | 1999-01-29 | |
| US60/118,381 | 1999-01-29 | ||
| PCT/US2000/001979 WO2000044776A1 (en) | 1999-01-29 | 2000-01-28 | Alpha-conotoxin peptides |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2743116A Division CA2743116C (en) | 1999-01-29 | 2000-01-28 | Alpha-conotoxin peptides with a 4/7 motif |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2361534A1 true CA2361534A1 (en) | 2000-08-03 |
| CA2361534C CA2361534C (en) | 2011-08-30 |
Family
ID=22378229
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2743116A Expired - Fee Related CA2743116C (en) | 1999-01-29 | 2000-01-28 | Alpha-conotoxin peptides with a 4/7 motif |
| CA2361534A Expired - Fee Related CA2361534C (en) | 1999-01-29 | 2000-01-28 | Alpha-conotoxin peptides |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2743116A Expired - Fee Related CA2743116C (en) | 1999-01-29 | 2000-01-28 | Alpha-conotoxin peptides with a 4/7 motif |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1147130A4 (en) |
| JP (1) | JP2002534996A (en) |
| AU (1) | AU770076B2 (en) |
| CA (2) | CA2743116C (en) |
| WO (1) | WO2000044776A1 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AUPR409401A0 (en) * | 2001-03-29 | 2001-04-26 | University Of Melbourne, The | Analgesic compound |
| AU2002245934B2 (en) * | 2001-03-29 | 2008-05-01 | John Down | Alpha conotoxin peptides with analgesic properties |
| CA2657532C (en) | 2006-07-18 | 2019-06-18 | University Of Utah Research Foundation | Methods for treating pain and screening analgesic compounds |
| US9284358B2 (en) | 2006-07-18 | 2016-03-15 | University Of Utah Research Foundation | Conotoxin peptides |
| JP2010500991A (en) * | 2006-08-17 | 2010-01-14 | エリビス ファーマシューティカルズ エービー | Cardioprotective compound |
| CN103483439B (en) * | 2012-06-15 | 2015-09-16 | 海南大学 | α O-superfamily conotoxin peptide, its pharmaceutical composition and purposes |
| US9469674B2 (en) * | 2012-08-07 | 2016-10-18 | Hainan University | α-conotoxin peptide, pharmaceutical composition and use thereof |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5432155A (en) * | 1993-06-29 | 1995-07-11 | The Salk Institute For Biological Studies | Conotoxins I |
| US5595972A (en) * | 1993-06-29 | 1997-01-21 | University Of Utah Research Foundation | Conotoxin peptides |
| US5514774A (en) * | 1993-06-29 | 1996-05-07 | University Of Utah Research Foundation | Conotoxin peptides |
| US5739276A (en) * | 1994-10-07 | 1998-04-14 | University Of Utah Research Foundation | Conotoxin peptides |
| US5719264A (en) * | 1994-10-07 | 1998-02-17 | Univ. Of Utah Research Foundation | Conotoxin peptides |
| US5670622A (en) * | 1996-02-15 | 1997-09-23 | University Of Utah Research Foundation | Conotoxin peptide PIIIA |
| US5672682A (en) * | 1996-03-18 | 1997-09-30 | University Of Utah Research Foundation | Conotoxin peptide PVIIA |
| AU735724B2 (en) * | 1996-11-18 | 2001-07-12 | University Of Utah Research Foundation | Use of conotoxin peptides ImI and MII as cardiovascular agents |
| US5780433A (en) * | 1996-12-06 | 1998-07-14 | University Of Utah Research Foundation | Use of α-conotoxin MII to treat disorders resulting from nicotine stimulated dopamine release |
| US5889147A (en) * | 1997-01-17 | 1999-03-30 | University Of Utah Research Foundation | Bromo-tryptophan conopeptides |
| US5866682A (en) * | 1997-05-15 | 1999-02-02 | University Of Utah Research Foundation | Conopeptides AuIA, AuIB and AuIC |
| US5969096A (en) * | 1998-06-26 | 1999-10-19 | The Salk Institute For Biological Studies | Conotoxin peptides |
-
2000
- 2000-01-28 EP EP00908382A patent/EP1147130A4/en not_active Withdrawn
- 2000-01-28 AU AU29735/00A patent/AU770076B2/en not_active Ceased
- 2000-01-28 WO PCT/US2000/001979 patent/WO2000044776A1/en active Application Filing
- 2000-01-28 CA CA2743116A patent/CA2743116C/en not_active Expired - Fee Related
- 2000-01-28 CA CA2361534A patent/CA2361534C/en not_active Expired - Fee Related
- 2000-01-28 JP JP2000596032A patent/JP2002534996A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AU2973500A (en) | 2000-08-18 |
| EP1147130A4 (en) | 2004-09-29 |
| CA2743116A1 (en) | 2000-08-03 |
| AU770076B2 (en) | 2004-02-12 |
| WO2000044776A1 (en) | 2000-08-03 |
| CA2361534C (en) | 2011-08-30 |
| CA2743116C (en) | 2016-06-21 |
| JP2002534996A (en) | 2002-10-22 |
| EP1147130A1 (en) | 2001-10-24 |
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