Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence
Patent
1994-10-07
1998-02-17
Tsang, Cecilia J.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
25 or more amino acid residues in defined sequence
514 12, A61K 3800, C07K 500, C07K 700, C07K 1600
Patent
active
057192642
ABSTRACT:
The present invention is directed to conotoxin peptides having 25-35 amino acids, six cysteines which form three disulfide bonds between the first and fourth, second and fifth, and third and sixth cysteines, respectively. The invention is directed to .delta.-conotoxin GmVIA having the formula Val-Lys-Pro-Cys-Arg-Lys-Glu-Gly-Gln-Leu-Cys-Asp-Pro-Ile-Phe-Gln-Asn-Cys-Cy s-Arg-Gly-Trp-Asn-Cys-Val-Leu-Phe-Cys-Val (SEQ ID NO:1). This peptide activates sodium channels. The invention is further directed to .mu.O-conotoxin peptides of the generic formula Ala-Cys-Xaa.sub.1 -Lys-Lys-Trp-Glu-Tyr-Cys-Ile-Val-Pro-Ile-Xaa.sub.2 -Gly-Phe-Xaa.sub.3 -Tyr-Cys-Cys-Pro-Gly-Leu-Ile-Cys-Gly-Pro-Phe-Val-Cys-Val, wherein Xaa.sub.1 is Arg or Ser, Xaa.sub.2 is Ile or Leu and Xaa.sub.3 is Ile or Val (SEQ ID NO:2). These peptides block sodium charmels. Examples of .mu.O-conotoxin peptides of the present invention are MrVIA, having the formula Ala-Cys-Arg-Lys-Lys-Trp-Glu-Tyr-Cys-Ile-Val-Pro-Ile-Ile-Gly-Phe-Ile-Tyr-Cy s-Cys-Pro-Gly-Leu-Ile-Cys-Gly-Pro-Phe-Val-Cys-Val (SEQ ID NO:3), and MrVIB, having the formula Ala-Cys-Ser-Lys-Lys-Trp-Glu-Tyr-Cys-Ile-Val-Pro-Ile-Leu-Gly-Phe-Val-Tyr-Cy s-Cys-Pro-Gly-Leu-Ile-Cys-Gly-Pro-Phe-Val-Cys-Val (SEQ ID NO:4).
REFERENCES:
Shon et al.; .delta.-conotoxin Gm VIA, A Novel Peptide from the Venom of us gloriamarts; biochemistry; 33, 1994 (Sep. 27,1994) 11420-11425.
Hasson Arik
McIntosh J. Michael
Olivera Baldomero M.
Shon Ki-Joon
Spira Micha E.
Harle Jennifer
Tsang Cecilia J.
Univ. of Utah Research Foundation
Yissum Research Development Co. of the Hebrew University of Jeru
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