Patent ID: 6767895
Filing Date: 2004-07-27
Classification: C07K

Abstract:
A substantially pure I-conotoxin peptide having the generic formula I: Xaa1-Xaa2-Xaa3-Xaa4-Cys-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Cys-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Cys-Cys-Xaa16-Xaa17-Xaa18-Cys-Cys-Xaa19-Xaa20-Gly-Xaa21-Cys-Xaa22-Xaa23-Xaa24-Xaa25-Xaa26-Xaa27-Xaa28-Xaa29-Xaa30-Xaa31-Cys-Xaa32-Xaa33-Xaa34-Xaa35-Xaa36-Xaa37-Xaa38-Xaa39-Xaa40-Xaa41 (SEQ ID NO: 1),wherein Xaa1 is des-Xaa1 or Gly; Xaa2 is des-Xaa2, Pro, hydroxy-Pro (Hyp), Ala, His or Gly; Xaa3 is des-Xaa3, Ser, Val, Pro, Hyp, Thr, g-Ser, g-Thr, g-Hyp or any non-natural hydroxylated amino acid; Xaa4 is des-Xaa4, Gly, Glu, &ggr;-carboxy-Glu (Gla), Phe, Pro, Hyp, Arg, Lys, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa5 is an aliphatic amino acid bearing linear or branched saturated hydrocarbon chains selected from the group consisting of Leu (D or L), Ile and Val or non-natural derivatives of the aliphatic amino acid, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys, any non-natural basic amino acid, Gly, Trp (D or L), neo-Trp, halo-Trp (D or L), or any aromatic non-natural amino acid; Xaa6 is Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys, any non-natural basic amino acid, Ala, an aliphatic amino acid bearing linear or branched saturated hydrocarbon chains selected from the group consisting of Leu (D or L), Ile and Val or non-natural derivatives of the aliphatic amino acid, Thr, Ser, g-Thr or g-Ser; Xaa7 is Gly, Asp, Glu, Gla, Asn, Gln or any non-natural acidic amino acid; Xaa8 is Gly, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys, any non-natural basic amino acid, Asp, Glu, Gla, Asn, Gln or any non-natural acidic amino acid; Xaa9 is Ala, Val, Met, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa10 is Ala, His, Ser, Thr, Pro, Hyp, g-Ser, g-Thr, g-Hyp, any non-natural hydroxylated amino acid, Asp, Glu, Gla, Asn, Gln, any non-natural acidic amino acid, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa11 is Gly, Ser, Thr, g-Ser, g-Thr, Asp, Glu, Gla, any non-natural acidic amino acid, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa12 is Asn, Phe, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr, any non-natural aromatic amino acid, Gln or Leu (D or L); Xaa13 is Ser, Thr, g-Ser, g-Thr or His; Xaa14 is Ala, Gla, Ser, Thr, g-Ser, g-Thr, His, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa15 is Asp, Glu, His or Gla; Xaa16 is des-Xaa16, Gly, His, Ser, Pro, Hyp, Thr, g-Ser, g-Thr, g-Hyp, any non-natural hyrdroxylated amino acid, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa17 is des-Xaa17, His, Ser, Thr, g-Ser, g-Thr, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys, any non-natural basic amino acid, Phe, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr,O-phospho-Tyr, nitro-Tyr or any non-natural aromatic amino acid; Xaa18 is Val, Asn, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa19 is des-Xaa19, Leu (D or L), Pro, Hyp, Phe, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any non-natural aromatic amino acid; Xaa20 is Gly, Ile, Ser, Thr, g-Ser, g-Thr, His, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys, any non-natural basic amino acid, Phe, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any non-natural aromatic amino acid; Xaa21 is Ser, Thr, g-Ser, g-Thr, an aliphatic amino acids bearing linear or branched saturated hydrocarbon chains such as Leu (D or L), Ile and Val and non-natural derivatives of the aliphatic amino acid, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys, any non-natural basic amino acid, Phe, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any non-natural aromatic amino acid; Xaa22 is Ala, Gln, Gla, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa23 is Ser, Pro, Hyp, Thr, g-Ser, g-Thr, g-Hyp, any non-natural hyrdroxylated amino acid, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa24 is Gln, Ser, Pro, Hyp, Thr, g-Ser, g-Thr, g-Hyp or any non-natural hyrdroxylated amino acid; Xaa25 is des-Xaa25, Ser, Thr, g-Ser or g-Thr; Xaa26 is des-Xaa26, Asn, Gln, Ser, Thr, g-Asn, g-Ser or g-Thr; Xaa27 is des-Xaa27, Val, Gla, Trp (D or L), neo-Trp, halo-Trp (D or L), any aromatic non-natural amino acid, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa28 is des-Xaa28, an aliphatic amino acids bearing linear or branched saturated hydrocarbon chains selected from the group consisting of Leu (D or L), Ile and Val and non-natural derivatives of the aliphatic amino acid; Xaa29 is des-Xaa29, an aliphatic amino acids bearing linear or branched saturated hydrocarbon chains selected from the group consisting of Leu (D or L), Ile and Val and non-natural derivatives of the aliphatic amino acid; Xaa30 is des-Xaa30, Ile, Ser, Pro, Hyp, Thr, g-Ser, g-Thr, g-Hyp, any non-natural hydroxylated amino acid, Phe, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any non-natural aromatic amino acid; Xaa31 is des-Xaa31 or Gly; Xaa32 is Ser, Thr, g-Ser, g-Thr, Trp (D or L), neo-Trp, halo-Trp (D or L), any aromatic non-natural amino acid, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa33 is Val, Ser, Thr, g-Ser, g-Thr, Tip (D or L), neo-Trp, halo-Trp (D or L) or any aromatic non-natural amino acid; Xaa34 is Gly, Ile, Asp, Glu, Gla, Asn, Ser, Thr, g-Asn, g-Ser or g-Thr; Xaa35 is des-Xaa35, Val, Met, Gln, Pro, Hyp, Ser, Thr, g-Ser, g-Thr, g-Hyp or any non-natural hydroxylated amino acid; Xaa36 is des-Xaa36, Val, Thr, Ser, g-Thr, g-Ser, Phe, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any non-natural aromatic amino acid; Xaa37 is des-Xaa37, Gln, Asn, Thr, Ser, g-Ser, g-Ser, g-Asn, Met, Leu, Phe, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr, any non-natural aromatic amino acid, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa38 is des-Xaa38, Leu, Ser, Thr, g-Ser, g-Thr, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa39 is des-Xaa39, Ile, Ala, Thr, Ser, g-Ser, g-Thr, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; Xaa40 is des-Xaa40, Asp, Lys, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,Nâ€²-dimethyl-Lys, N,Nâ€²,Nâ€³-trimethyl-Lys or any non-natural basic amino acid; and Xaa41 is des-Xaa41, Phe, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any non-natural aromatic amino acid, with the proviso that the peptide is not J029 (SEQ ID NO:2).