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US 2003/0166560 A1Published application
P-superfamily conopeptides
OwnerDavid Hooper, James E. Garrett +5inventors
InventorsDavid Hooper, James E. Garrett, Gloria P. Corpuz, Lourdes J. Cruz, Baldomero M. Olivera, J. Michael McIntosh, Robert M. Jones
Life of this patent
Estimating the term…
Abstract
The present invention is directed to P-superfamily conopeptides, to DNA encoding precursors of the P-superfamily conopeptides and to the precursor peptides.
Claims33
A substantially pure conopeptide having the sequence
- Xaa1-Xaa2-Cys-Xaa3-Xaa4-Xaa5-Xaa6-Cys-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Cys-Xaa12-Xaa13-Xaa14-Cys-Xaa15-Xaa16-Cys-Xaa17-Xaa18-Xaa19-Xaa20-Xaa21-Cys-Xaa22-Xaa23-Xaa24-Xaa25-Xaa26-Xaa27-Xaa28
- where Xaa1 may be Ser, Ala, Asn, Leu, Thr, Gly, g-Thr or g-Ser;
- Xaa2 may be des-Xaa2, Ser, Thr, Gly, g-Thr or g-Ser;
- Xaa3 may be Asn, Gin, Gly, Thr, Ser, g-Thr or g-Ser;
- Xaa4 may be des-Xaa4 or Gly;
- Xaa5 may be des-Xaa5, Asn or Asp;
- Xaa6 may be Ser, Thr, Pro, Hyp (hydroxy-Pro), g-Thr or g-Ser;
- Xaa7 may be Asn, Gin, Thr, Ser, g-Thr or g-Ser;
- Xaa8 may be Glu, Ser, Asn, Met, Thr, Gla (y-carboxy-Glu), Nle (norleucine), Asp, Gin, g-Thr or g-Ser;
- Xaa9 may be His, Ser, Asp, Thr, g-Thr or g-Ser;
- Xaa10 may be Ser, Ala, Pro, Hyp, Thr, g-Thr or g-Ser;
- Xaa 11 may be Asp, Glu Gla or any synthetic acidic amino acid;
- Xaa12 may be des-Xaa12, Glu, Asp, Pro, Hyp, Gla, Ala, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, mono-halo-Tyr, ortho-125I-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr or any synthetic acidic amino acid;
- Xaa13 may be Ser, Asn, Gly, Thr, Hyp, g-Thr, g-Ser or any synthetic hydroxy containing amino acid;
- Xaa14 may be His, Thr, Phe, Asn, Ile, Ser, Gin, g-Ser, g-Thr, any synthetic hydroxy containing amino acid, Trp (D or L), neo-Trp, halo-Trp (D or L) or any synthetic aromatic amino acid;
- Xaa15 may be Ile, Ser, Asp, Glu, Gla, any synthetic amino acid, Thr, g-Ser, g-Thr, any synthetic hydroxy containing amino acid, Tyr, meta-Tyr, ortho-Tyr, nor-Tyr, ortho-125I-Tyr, mono-halo-Tyr, di-halo-Tyr, O-sulpho-Tyr, O-phospho-Tyr or nitro-Tyr;
- Xaa16 may be des-Xaa16, Thr, Ser, g-Thr, g-Ser or any synthetic hydroxy containing amino acid;
- Xaa17 may be des-Xaa17, Asp, Glu, Gla or any synthetic acidic amino acid;
- Xaa18 may be Thr, Leu, Ile, Val, Ser, g-Thr, g-Ser or any synthetic hydroxy containing amino acid;
- Xaa19 may be Phe, His, Gly, Glu, Asp, Gla, any synthetic acidic amino acid, Ser, Thr, g-Ser, g-Thr, any synthetic hydroxy containing amino acid, Trp (D or L), neo-Trp, halo-Trp (D or L) or any synthetic aromatic amino acid;
- Xaa20 may be Ser, Thr, Ala, Asp, Asn, Gin, g-Ser, g-Thr, His, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,N′-dimethyl-Lys, N,N′,N″-trimethyl-Lys or any synthetic basic amino acid;
- Xaa21 may be Gly, Gin, Asn, His, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,N′-dimethyl-Lys, N,N′,N″-trimethyl-Lys or any synthetic basic amino acid;
- Xaa22 may be Gly, Glu, Asp, Gla, any synthetic acidic amino acid, Ile, His, Arg, omithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,N′-dimethyl-Lys, N,N′,N″-trimethyl-Lys or any synthetic basic amino acid;
- X23aa may be des-Xaa23, Ile, Ala, Ser, Pro, Hyp, Phe, Thr, g-Thr, g-Ser or any synthetic hydroxy containing amino acid;
- Xaa24 may be des-Xaa24, Ile, Val, Thr, Asp, Phe, Ser, g-Thr, g-Ser or any synthetic hydroxy containing amino acid;
- Xaa25 may be des-Xaa25, Met, Nle, His, Arg, omithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,N′-dimethyl-Lys, N,N′,N″-trimethyl-Lys or any synthetic basic amino acid;
- Xaa26 may be des-Xaa26, His, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,N′-dimethyl-Lys, N,N′,N″-trimethyl-Lys or any synthetic basic amino acid;
- Xaa27 may be des-Xaa27, Leu, Asn, Gln, Glu, Asp, Gla or any synthetic amino acid;
- and Xaa28 may be des-Xaa28, Ile, His, Arg, ornithine, homo-Lys, homoarginine, nor-Lys, N-methyl-Lys, N,N′-dimethyl-Lys, N,N′,N″-trimethyl-Lys or any synthetic basic amino acid.
26 more elements
A substantially pure peptide selected from the group consisting of:
- Ser-Cys-Asn-Asn-Ser-Cys-Asn-Xaal-His-Ser-Asp-Cys-Xaal-Ser-His-Cys-Ile-Cys-Thr-Phe-Ser-Gly-Cys-Lys-Ile-Ile-Leu-Ile (SEQ ID NO:2);
- Ser-Cys-Asn-Asn-Ser-Cys-Asn-Xaa1-His-Ser-Asp-Cys-Xaa1-Ser-His-Cys-Ile-Cys-Thr-Phe-Arg-Gly-Cys-Gly-Ala-Val-Asn (SEQ ID NO:3);
- Ala-Ser-Cys-Gly-Gly-Thr-Cys-Thr-Xaa1-Ser-Ala-Asp-Cys-Xaa3-Ser-Thr-Cys-Ser-Thr-Cys-Leu-His-Ala-Gln-Cys-Xaa1-Ser-Thr (SEQ ID NO:4);
- Ser-Cys-Gly-Gly-Thr-Cys-Thr-Xaa1-Ser-Ala-Asp-Cys-Xaa3-Ser-Thr-Cys-Ser-Thr-Cys-Leu-His-Ala-Gln-Cys-Xaa1 (SEQ ID NO:5);
- Ala-Cys-Thr-Gly-Ser-Cys-Asn-Ser-Asp-Ser-Xaa1-Cys-Xaa5-Asn-Phe-Cys-Asp-Cys-Ile-Gly-Thr-Arg-Cys-Xaa1-Ala-Gln-Lys (SEQ ID NO:6);
- Ser-Cys-Asn-Asn-Ser-Cys-Gln-Ser-His-Ser-Asp-Cys-Ala-Ser-His-Cys-Ile-Cys-Thr-Phe-Arg-Gly-Cys-Gly-Ala-Val-Asn (SEQ ID NO:7);
- Asn-Gly-Cys-Asn-Gly-Asn-Thr-Cys-Ser-Asn-Ser-Xaa3-Cys-Xaa3-Asn-Asn-Cys-Xaa5-Cys-Asp-Thr-Xaa1-Asp-Asp-Cys-His-Xaa3-Asp-Arg-Arg-Xaa1-His (SEQ ID NO:
- 8);
- Leu-Thr-Cys-Asn-Asp-Xaa3-Cys-Gln-Met-His-Ser-Asp-Cys-Gly-Ile-Cys-Xaa1-Cys-Val-Xaa1-Asn-Lys-Cys-Ile-Phe-Phe-Met (SEQ ID NO:9);
- Gly-Cys-Asn-Asn-Ser-Cys-Gln-Xaa1-His-Ser-Asp-Cys-Xaa1-Ser-His-Cys-Ile-Cys-Thr-Phe-Arg-Gly-Cys-Gly-Ala-Val-Asn (SEQ ID NO:
- 10);
- and
- Gly-Cys-Asn-Asn-Ser-Cys-Gln-Xaa1-His-Ser-Asp-Cys-Xaa1-Ser-His-Cys-Ile-Cys-Thr-Ser-Arg-Gly-Cys-Gly-Ala-Val-Asn (SEQ ID NO:11),
- wherein Xaa1 is Glu or γ-carboxy-Glu;
- Xaa3 is Pro or hydroxy-Pro;
- Xaa5 is Tyr, 125I-Tyr, mono-iodo-Tyr, di-iodo-Tyr, O-sulpho-Tyr or O-phospho-Tyr;
- and the C-terminus contains an amide group or a carboxyl group.
14 more elements
An isolated nucleic acid encoding a P-superfamily conopeptide precursor having an amino acid sequence selected from the groups consisting of the amino acid sequences set forth in SEQ ID NOs:18, 20, 22, 24, 26, 28, 30, 32 and 34.
An isolated P-superfamily conopeptide precursor having an amino acid sequence selected from the group consisting of the amino acid sequences set forth in SEQ ID NOs:18, 20, 22, 24, 26, 28, 30, 32 and 34.
Dependencies are inferred from the claim text.