University of Utah Research Foundation

Other

Cognetix, Inc.

The Salk Institute for Biological Studies

Maren Watkins

Baldomero M Olivera

David R Hillyard

Robert M Jones

J Michael McIntosh

Lourdes J Cruz

Richard T Layer

Julita S Imperial

A Grey Craig

R Tyler McCabe

Elsie C Jimenez

John D Wagstaff

William R Gray

David Griffen

Craig S Walker

Richard Jacobsen

Reshma Shetty

Michelle Grilley

Jean E Rivier

Doju Yoshikami

James E Garrett

Alma L Burlingame

Ki-Joon Shon

Gregory S Shen

G Edward Cartier

John Dykert

Michael Fainzilber

Clark Colledge

Karel S Kits

David Griffin

Robert Schoenfeld

J Michael Mcintosh

The invention relates to relatively short peptides (termed &#x3b1;-conotoxins herein), about 10-30 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds.

&#x3b1;-Conotoxin peptides

Alpha-conotoxin peptides

Apha-conotoxin peptides

The present invention is directed to &#x3b2;-superfamily conotoxin peptides, derivatives or pharmaceutically acceptable salts thereof. The present invention is further directed to the use of this peptide, derivatives thereof and pharmaceutically acceptable salts thereof for the treatment of disorders associated with voltage-gated ion channels, ligand gated channels and other receptors. The invention is further directed to nucleic acid sequences encoding the &#x3b2;-superfamily conotoxin peptides and encoding &#x3b2;-superfamily conotoxin propeptides, as well as the &#x3b2;-superfamily conotoxin propeptides.

&#x3b2;-Superfamily conotoxins

The invention relates to relatively short peptides (termed &agr;-conotoxins herein), about 10-30 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds.

&agr;-conotoxin peptides

The invention relates to relatively short peptides (termed I-conotoxins herein), about 30-50 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include four disulfide bonds.

I-superfamily conotoxins

The invention relates to relatively short peptides (termed O-Superfamily conotoxins herein), about 20-40 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds.

O-superfamily conotoxin peptides

The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr -contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.

Contulakin-G, analogs thereof and uses therefor

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

Contulakin-G, analogs thereof and uses thereof

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Salt Lake City, UT, United States of America

Maren Watkins