University of California

The Weizmann Institute of Science

Other

Michael Fainzilber

Alma L Burlingame

Katalin F Medzihradszky

Robert J Chalkley

Darren Tyson

Ralph A Bradshaw

Zsuzsanna Darula

Eran Perlson

Baldomero M Olivera

Lourdes J Cruz

Maren Watkins

Julita S Imperial

Craig S Walker

Reshma Shetty

Clark Colledge

Karel S Kits

Post-translational O-sulfonation of a serine or threonine residue of proteins is detected, optionally comparatively, wherein the detected O-sulfonation is detected under a first physiological condition, and is compared with a control O-sulfonation detected under a second physiological condition, and a difference between the detected and control O-sulfonations indicates a difference between the first and second physiological conditions. Predetermined changes in physiological conditions are used to infer specific changes in O-sulfonation. Proteins are modified by introducing a predetermined change in O-sulfonation at a serine or threonine residue of the protein, and optionally, detecting a resultant change in O-sulfonation. These methods include introducing or increasing O-sulfonation, eliminating or reducing O-sulfonation; and derivatizing or substituting O-sulfonation.

Protein O-sulfonation

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 &ggr;-carboxyglutamate residues. More specifically, the present invention is directed to &ggr;-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 &ggr;-conopeptides, specific pro-&ggr;-conopeptides and nucleic acids encoding the pro-&ggr;-conopeptides. The invention also includes pharmaceutically acceptable salts of the conopeptides. These conopeptides are useful as agonists of neuronal pacemaker calcium channels.

Gamma-conopeptides

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Rehovot, Israel

Michael Fainzilber