Inventors:
Michael Fainzilber - Haifa, IL
Karel Kits - Amsterdam, NL
Alma Burlingame - Sausalito CA, US
Baldomero Olivera - Salt Lake City UT, US
Craig Walker - Salt Lake City UT, US
Maren Watkins - Salt Lake City UT, US
Reshma Shetty - Salt Lake City UT, US
Lourdes Cruz - Manila, PH
Julita Imperial - Salt Lake City UT, US
Clark Colledge - Draper UT, US
Assignee:
Cognetix Inc. - Salt Lake City UT
University of Utah Research Foundation - Salt Lake City UT
International Classification:
C07K 7/08, C07K 14/435
US Classification:
530326000, 530327000, 530328000
Abstract:
This invention relates to relatively short peptides about 25-40 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogs to the naturally available peptides, and which include three cyclizing disulfide linkages and one or more γcarboxyglutamate residues. More specifically, the present invention is directed to γ-conopeptides having the general formula I: Xaa-Cys-Xaa-Cys-Xaa-Xaa-Cys-Cys-Xaa-Cys-Xaa-Cys-Xaa(SEQ ID NO:1), as described herein; or having the general formula II: Xaa-Cys-Xaa-Cys-Xaa-Xaa-Cys-Cys-Xaa-Xaa-Cys-Xaa-Cys-Xaa(SEQ ID NO:2), as defined herein; or having the general formula III: Xaa-Cys-Xaa-Cys-Xaa-Xaa-Xaa-Cys-Cys-Ser-Asn-Ser-Cys-Asp-Xaa-Cys-Xaa(SEQ ID NO:3), as described herein; or having the general formula IV: Xaa-Cys-Xaa-Cys-Xaa-Xaa-Xaa-Cys-Cys-Ser-Asn-Ser-Cys-Asp-Xaa-Cys-Xaa(SEQ ID NO:4), as described herein; or having the general formula V: Xaa-Xaa-Cys-Xaa-Xaa-Phe-Xaa-Cys-Thr-Xaa-Ser-Xaa-Cys-Cys-Ser-Asn-Ser-Cys-Asp-Gln-Thr-Tyr-Cys-Xaa-Leu-Xaa(SEQ ID NO:5), as described herein. The invention further relates to specific γ-conopeptides, specific pro-γ-conopeptides and nucleic acids encoding the pro-γ-conopeptides. The invention also includes pharmaceutically acceptable salts of the conopeptides. These conopeptides are useful as agonists of neuronal pacemaker calcium channels.