Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Univ. of Utah Research Foundation

Arik Hasson

Baldomero M Olivera

J Michael McIntosh

Ki-Joon Shon

Micha E Spira

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).

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Jerusalem, Israel

Arik Hasson