Alpha-conotoxin peptides
AssigneesCognetix, Inc., University of Utah Research Foundation
InventorsMaren WATKINS, Baldomero M. OLIVERA, David R. HILLYARD, J. Michael MCINTOSH, Robert M. JONES
Life of this patent
Estimating the term…
Abstract
The invention relates to relatively short peptides (termed α-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.
Claims10
A substantially pure α-conotoxin peptide selected from the group consisting of:
- (SEQ ID NO:
- 4)
- Asp-Xaa1-Cys-Cys-Ser-Asp-Ser-Arg-Cys-Gly-Xaa2-
- Asn-Cys-Leu;
- (SEQ ID NO:
- 5)
- Ala-Cys-Cys-Ser-Asp-Arg-Arg-Cys-Arg-Xaa3-Arg-Cys;
- (SEQ ID NO:
- 6)
- Phe-Thr-Cys-Cys-Arg-Arg-Gly-Thr-Cys-Ser-Gln-His-
- Cys;
- (SEQ ID NO:
- 7)
- Asp-Xaa4-Cys-Cys-Arg-Arg-His-Ala-Cys-Thr-Leu-
- Ile-Cys;
- (SEQ ID NO:
- 8)
- Asp-Xaa4-Cys-Cys-Arg-Xaa5-Xaa5-Cys-
- Thr-Leu-Ile-Cys;
- (SEQ ID NO:
- 10)
- Gly-Gly-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ala-Xaa3-
- Arg-Cys;
- (SEQ ID NO:
- 11)
- Ile-Ala-Xaa3-Asp-Ile-Cys-Cys-Ser-Xaa1-Xaa5-
- Asp-Cys-Asn-His-Xaa2-Cys-Val;
- and
- (SEQ ID NO:
- 12)
- Gly-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Xaa2-His-Gln-Cys,
- wherein Xaa1 is Glu or γ-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.
A substantially pure α-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 γ-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;
- Xaa2 is Pro or hydroxy-Pro;
- Xaas 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.
A substantially pure α-conotoxin peptide selected from the group consisting of:
- (SEQ ID NO:
- 22)
- Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Ser-Asn-Met-Cys;
- (SEQ ID NO:
- 23)
- Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Arg-Gln-Asn-Asn-Ala-Xaa1-Xaa4-Cys-Arg;
- (SEQ ID NO:
- 24)
- Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-
- Arg;
- (SEQ ID NO:
- 25)
- Xaa5-Xaa1-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-
- Cys-Arg;
- (SEQ ID NO:
- 26)
- Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-
- Asp;
- (SEQ ID NO:
- 27)
- Xaa5-Arg-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-
- Arg;
- (SEQ ID NO:
- 28)
- Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Gly-Ile-Cys-
- Arg;
- (SEQ ID NO:
- 29)
- Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Thr-
- Cys-Arg;
- (SEQ ID NO:
- 30)
- Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Val-
- Cys-Arg;
- (SEQ ID NO:
- 31)
- Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Ile-Asp-His-Xaa5-Xaa1-Ile-Cys-
- Arg;
- (SEQ ID NO:
- 32)
- Xaa5-Gln-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-
- Arg-Arg-Arg-Arg;
- (SEQ ID NO:
- 33)
- Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Val-Asn-His-Xaa5-Xaa1-Leu-Cys;
- (SEQ ID NO:
- 35)
- Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys;
- (SEQ ID NO:
- 36)
- Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Xaa2-Thr-Gln-Xaa1-Xaa5-Cys-Arg-
- Xaa1-Ser;
- (SEQ ID NO:
- 37)
- Xaa5-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-Ala-Cys-Ser-Gly-Asn-Asn-Xaa5-Xaa1-Phe-Cys-Arg-
- Gln;
- (SEQ ID NO:
- 39)
- Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Ala-Met-Asn-Asn-Xaa5-Asp-Xaa4-Cys;
- (SEQ ID NO:
- 40)
- Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Phe-Leu-Asn-Asn-Xaa5-Asp-Xaa4-Cys;
- (SEQ ID NO:
- 41)
- Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ile-Ala-Xaa2-Asn-Xaa5-His-Met-Cys-Gly;
- (SEQ ID NO:
- 43)
- Gly-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Val-Cys-Arg-
- Gln;
- (SEQ ID NO:
- 44)
- Gly-Cys-Cys-Ser-Arg-Xaa5-Ala-Cys-Ile-Ala-Asn-Asn-Xaa5-Asp-Leu-Cys;
- (SEQ ID NO:
- 45)
- Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Val-Xaa1-His-Xaa5-Xaa1-Leu-Cys-
- Arg-Arg-Arg-Arg;
- (SEQ ID NO:
- 46)
- Gly-Gly-Cys-Cys-Ser-Phe-Xaa5-Ala-Cys-Arg-Xaa2-Xaa5-Arg-Xaa5-Xaa1-Met-
- Cys-Gly;
- (SEQ ID NO:
- 47)
- Xaa5-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Ser-Ser-His-Xaa5-Xaa1-Leu-
- Cys-Gly;
- (SEQ ID NO:
- 48)
- Xaa5-Gln-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Val-Gly-His-Xaa5-Xaa1-Leu-
- Cys-Gly;
- (SEQ ID NO:
- 49)
- Xaa6-Val-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Val-Gly-His-Xaa5-Xaa1-Ile-Cys-
- Gly;
- (SEQ ID NO:
- 50)
- Gly-Cys-Cys-Ser-Arg-Xaa5-Xaa5-Cys-Ile-Ala-Asn-Asn-Xaa5-Asp-Leu-Cys;
- (SEQ ID NO:
- 51)
- Xaa5-Gln-Cys-Cys-Ser-His-Leu-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-Cys-
- Arg;
- (SEQ ID NO:
- 52)
- Gly-Cys-Cys-Ser-Xaa4-Phe-Asp-Cys-Arg-Met-Met-Phe-Xaa5-Xaa1-Met-Cys-
- Gly-Xaa3-Arg;
- (SEQ ID NO:
- 53)
- Gly-Gly-Cys-Cys-Ser-Phe-Ala-Ala-Cys-Arg-Xaa2-Xaa4-Arg-Xaa5-Xaa1-Met-
- Cys-Gly;
- (SEQ ID NO:
- 54)
- Gly-Gly-Cys-Cys-Phe-His-Xaa5-Val-Cys-Xaa4-Ile-Asn-Leu-Leu-Xaa1-Met-Cys-
- Arg-Gln-Arg;
- (SEQ ID NO:
- 55)
- Ser-Ala-Thr-Cys-Cys-Asn-Xaa4-Xaa5-Xaa5-Cys-Xaa4-Xaa1-Thr-Xaa4-Xaa5-
- Xaa1-Ser-Cys-Leu;
- (SEQ ID NO:
- 56)
- Ala-Cys-Cys-Ala-Xaa4-Xaa5-Xaa5-Cys-Phe-Xaa1-Ala-Xaa4-Xaa5-Xaa1-Arg-Cys-
- Leu;
- (SEQ ID NO:
- 57)
- Asn-Ala-Xaa1-Cys-Cys-Xaa4-Xaa4-Xaa5-Xaa5-Cys-Xaa4-Xaa1-Ala-Xaa4-Xaa5-
- Xaa1-Ile-Cys-Leu;
- (SEQ ID NO:
- 170)
- Xaa1-Cys-Cys-Thr-Asn-Xaa5-Val-Cys-His-Ala-Xaa1-His-Gln-Xaa1-Leu-Cys-
- Ala-Arg-Arg-Arg;
- (SEQ ID NO:
- 171)
- Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Ser-Asn-Leu-Cys;
- (SEQ ID NO:
- 172)
- Xaa1-Cys-Cys-Thr-Asn-Xaa5-Val-Cys-His-Val-Xaa1-His-Gln-Xaa1-Leu-Cys-
- Ala-Arg-Arg-Arg;
- (SEQ ID NO:
- 173)
- Xaa6-Xaa1-Cys-Cys-Ser-Xaa4-Xaa5-Ala-Cys-Asn-Leu-Asp-His-Xaa5-Xaa1-Leu-
- Cys;
- (SEQ ID NO:
- 174)
- Xaa5-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Asn-Ser-Thr-His-Xaa5-Xaa1-Leu-
- Cys-Gly;
- (SEQ ID NO:
- 175)
- Leu-Asn-Cys-Cys-Met-Ile-Xaa5-Xaa5-Cys-Xaa3-Xaa2-Xaa2-Xaa4-Gly-Asp-Arg-
- Cys-Ser-Xaa1-Val-Arg;
- (SEQ ID NO:
- 176)
- 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:
- 177)
- Leu-Gly-Cys-Cys-Asn-Val-Thr-Xaa5-Cys-Xaa3-Xaa1-Xaa2-Xaa4-Gly-Asp-Xaa2-
- Cys-Asn-Xaa1-Val-Arg;
- (SEQ ID NO:
- 179)
- Leu-Asn-Cys-Cys-Ser-Ile-Xaa5-Gly-Cys-Xaa3-Asn-Xaa1-Xaa4-Xaa2-Asp-Arg-
- Cys-Ser-Xaa2-Val-Arg;
- (SEQ ID NO:
- 180)
- Gly-Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Xaa4-Phe-Asn-Asn-Xaa5-Gln-Met-Cys-
- Arg;
- (SEQ ID NO:
- 181)
- Gly-Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Asn-Leu-Asn-Asn-Xaa5-Gln-Met-Cys-
- Arg;
- (SEQ ID NO:
- 182)
- Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Xaa4-Ala-Asn-Asn-Gln-Ala-Xaa4-Cys-Asn;
- (SEQ ID NO:
- 183)
- Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Thr-His-Xaa5-Xaa1-Leu-Cys;
- (SEQ ID NO:
- 184)
- Gly-Gly-Cys-Cys-Ser-Xaa4-Xaa5-Ala-Cys-Ser-Val-Xaa1-His-Gln-Asp-Leu-Cys-
- Asp;
- (SEQ ID NO:
- 185)
- 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:
- 186)
- Xaa6-Asn-Cys-Cys-Ser-Ile-Xaa5-Gly-Cys-Xaa3-Xaa1-Xaa2-Xaa4-Gly-Asp-Xaa2-
- Cys-Ser-Xaa1-Val-Arg;
- (SEQ ID NO:
- 187)
- Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Leu-Xaa1-His-Xaa5-Asn-Ala-Cys;
- (SEQ ID NO:
- 188)
- Gly-Cys-Cys-Ser-Asn-Xaa5-Ile-Cys-Xaa4-Phe-Asn-Asn-Xaa5-Arg-Ile-Cys-Arg;
- (SEQ ID NO:
- 189)
- Xaa1-Cys-Cys-Ser-Gln-Xaa5-Xaa5-Cys-Arg-Xaa3-Xaa2-His-Xaa5-Xaa1-Leu-Cys-
- Ser;
- (SEQ ID NO:
- 190)
- Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Gln-His-Ile-Cys;
- (SEQ ID NO:
- 191)
- Gly-Cys-Cys-Ala-Val-Xaa5-Ser-Cys-Arg-Leu-Arg-Asn-Xaa5-Asp-Leu-Cys-Gly-
- Gly;
- (SEQ ID NO:
- 192)
- Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa5-His-Ile-Cys;
- (SEQ ID NO:
- 193)
- Thr-Xaa5-Xaa1-Xaa1-Cys-Cys-Xaa5-Asn-Xaa5-Xaa5-Cys-Phe-Ala-Thr-Asn-Ser-
- Asp-Ile-Cys-Gly;
- (SEQ ID NO:
- 194)
- Asp-Ala-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Gly-Xaa2-His-Gln-Asp-Leu-Cys;
- (SEQ ID NO:
- 195)
- Xaa1-Asp-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-Asp-Leu-Cys;
- (SEQ ID NO:
- 196)
- Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Ser-Asn-Ala-His-Ile-Cys;
- (SEQ ID NO:
- 197)
- Xaa1-Asp-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-Asp-Met-Cys;
- (SEQ ID NO:
- 198)
- Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Ile-Cys;
- (SEQ ID NO:
- 199)
- Gly-Cys-Cys-Gly-Asn-Xaa5-Ser-Cys-Ser-Ile-His-Ile-Xaa5-Xaa4-Val-Cys-Asn;
- (SEQ ID NO:
- 200)
- Thr-Asp-Ser-Xaa1-Xaa1-Cys-Cys-Leu-Asp-Ser-Arg-Cys-Ala-Gly-Gln-His-Gln-
- Asp-Leu-Cys-Gly;
- (SEQ ID NO:
- 201)
- Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Xaa4-Ala-Asn-Asn-Gln-Ala-Xaa4-Cys-
- Asn;
- (SEQ ID NO:
- 202)
- Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Val-Asn-Asn-Xaa5-Asp-Ile-Cys;
- (SEQ ID NO:
- 203)
- Gly-Xaa2-Cys-Cys-Ile-Asn-Asp-Ala-Cys-Arg-Ser-Xaa2-His-Xaa5-Gln-Xaa4-Cys-
- Ser;
- (SEQ ID NO:
- 204)
- Gly-Cys-Cys-Xaa4-Asn-Ile-Ala-Cys-Arg-Ile-Asn-Asn-Xaa5-Arg-Xaa4-Cys-Arg;
- (SEQ ID NO:
- 205)
- Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Arg-Phe-Asn-Xaa4-Xaa5-Xaa2-Xaa4-Cys-
- Gly;
- (SEQ ID NO:
- 206)
- Asp-Xaa1-Cys-Cys-Ala-Ser-Xaa5-Xaa5-Cys-Arg-Leu-Asn-Asn-Xaa5-Xaa4-Val-
- Cys-His;
- (SEQ ID NO:
- 207)
- Gly-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-Xaa3-Gln-Asn-Asn-Ala-Xaa1-Xaa4-Cys-
- Arg-Xaa1-Ser;
- (SEQ ID NO:
- 208)
- Gly-Cys-Cys-Ser-His-Xaa5-Xaa5-Cys-Ala-Gln-Asn-Asn-Gln-Asp-Xaa4-Cys;
- (SEQ ID NO:
- 209)
- Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ser-Gly-Asn-Asn-Arg-Xaa1-Xaa4-Cys-Arg-
- Xaa1-Ser;
- (SEQ ID NO:
- 210)
- Asp-Xaa5-Cys-Cys-Ser-Xaa4-Xaa5-Asp-Cys-Gly-Ala-Asn-His-Xaa5-Xaa1-Ile-
- Cys-Gly;
- (SEQ ID NO:
- 211)
- Xaa1-Cys-Cys-Ser-Gln-Xaa5-Xaa5-Cys-Arg-Xaa3-Xaa2-His-Xaa5-Xaa1-Leu-Cys-
- Ser;
- (SEQ ID NO:
- 212)
- Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Ala-Gly-Asn-Asn-Xaa5-His-Ile-Cys;
- (SEQ ID NO:
- 213)
- Gly-Cys-Cys-Ser-Asp-Xaa5-Ser-Cys-Asn-Val-Asn-Asn-Xaa5-Asp-Xaa4-Cys;
- (SEQ ID NO:
- 214)
- Xaa1-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-Ser-Val-Gly-His-Gln-Asp-Met-Cys-
- Arg;
- (SEQ ID NO:
- 215)
- Gly-Gly-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Leu-Val-Asn-His-Leu-Xaa1-Met-Cys;
- (SEQ ID NO:
- 216)
- Arg-Asp-Xaa5-Cys-Cys-Phe-Asn-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa5-Gln-Ile-
- Cys;
- (SEQ ID NO:
- 217)
- Cys-Cys-Ser-Asp-Xaa5-Ser-Cys-Xaa3-Arg-Leu-His-Ser-Leu-Ala-Cys-Thr-Gly-
- Ile-Val-Asn-Arg;
- (SEQ ID NO:
- 218)
- Cys-Cys-Thr-Asn-Xaa5-Ala-Cys-Leu-Val-Asn-Asn-Ile-Arg-Phe-Cys-Gly;
- (SEQ ID NO:
- 219)
- Asp-Xaa1-Cys-Cys-Ser-Asp-Xaa5-Arg-Cys-His-Gly-Asn-Asn-Arg-Asp-His-Cys-
- Ala;
- (SEQ ID NO:
- 220)
- Asp-Cys-Cys-Ser-His-Xaa5-Leu-Cys-Arg-Leu-Phe-Val-Xaa5-Gly-Leu-Cys-Ile;
- (SEQ ID NO:
- 221)
- Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Xaa2-Val-Arg-Xaa4-Xaa5-Asp-Leu-Cys-Arg;
- (SEQ ID NO:
- 222)
- Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asn-Asn-Xaa5-His-Ile-Cys;
- (SEQ ID NO:
- 223)
- Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Xaa2-Val-Arg-Xaa4-Ser-Asp-Met-Cys;
- (SEQ ID NO:
- 224)
- Gly-Gly-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Xaa2-Val-His-Phe-Xaa5-His-Ser-Cys;
- (SEQ ID NO:
- 225)
- Val-Cys-Cys-Ser-Asn-Xaa5-Val-Cys-His-Val-Asp-His-Xaa5-Xaa1-Leu-Cys-Arg-
- Arg-Arg-Arg;
- (SEQ ID NO:
- 226)
- Gly-Cys-Cys-Ser-His-Xaa5-Val-Cys-Asn-Leu-Ser-Asn-Xaa5-Gln-Ile-Cys-Arg;
- (SEQ ID NO:
- 227)
- Xaa6-Xaa1-Cys-Cys-Ser-His-Xaa5-Ala-Cys-Asn-Val-Asp-His-Xaa5-Xaa1-Ile-
- Cys-Arg;
- (SEQ ID NO:
- 228)
- Gly-Cys-Cys-Ser-Asn-Xaa5-Ala-Cys-Leu-Val-Asn-His-Ile-Arg-Phe-Cys-Gly;
- (SEQ ID NO:
- 229)
- Asp-Cys-Cys-Asp-Asp-Xaa5-Ala-Cys-Thr-Val-Asn-Asn-Xaa5-Gly-Leu-Cys-Thr;
- and
- (SEQ ID NO:
- 230)
- Gly-Cys-Cys-Ser-Asn-Xaa5-Xaa5-Cys-Ile-Ala-Xaa2-Asn-Xaa5-His-Met-Cys-Gly-
- Gly-Arg-Arg,
- wherein Xaa1 is Glu or γ-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.
A substantially pure α-conotoxin peptide selected from the group consisting of:
- (SEQ ID NO:
- 231)
- Cys-Cys-Thr-Ile-Xaa5-Ser-Cys-Xaa4-Xaa1-Xaa2-Xaa2-
- Xaa2-Ile-Xaa2-Ala-Cys-Val-Phe
- and
- (SEQ ID NO:
- 232)
- Gly-Cys-Cys-Gly-Asn-Xaa5-Ala-Cys-Ser-Gly-Ser-Ser-
- Xaa2-Asp-Ala-Xaa5-Ser-Cys,
- wherein Xaa1 is Glu or γ-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.
Dependencies are inferred from the claim text.