Nps Pharmaceuticals, Inc.

The Brigham and Women's Hospital, Inc.

Cognetix, Inc.

Other

University of Utah Research Foundation

Xenome Limited

James E Garrett

Baldomero M Olivera

Robert M Jones

Edward M Brown

Steven C Hebert

J Michael McIntosh

Lourdes J Cruz

Gloria P Corpuz

Bradford C Van Wagenen

Manuel F Balandrin

Maren Watkins

Thomas M Stormann

Eric G Del Mar

Lance G Hammerland

Grzegorz Bulaj

Edward F Nemeth

Forrest H Fuller

G Edward Cartier

John D Wagstaff

Rachel T Simin

Laura L Storjohann

James G Busby

Olga Buczek

Ian Goodsell

The invention relates to relatively short conotoxin peptides, about 10-20 residues in length as described herein, 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. These conotoxin peptides have analgesic activity and are thus useful for treating or preventing pain.

Conotoxin peptides

The present invention features G-protein fusion receptors and chimeric GABAreceptors (GABARs), nucleic acid encoding such receptors, and the use of such receptors and nucleic acid. G-protein fusion receptors comprise at least one domain from a CaR, an mGluR, and/or a GABAreceptor fused directly or through a linker to a guanine nucleotide-binding protein (G-protein). Chimeric GABARs comprise at least one of a GABAR extracellular domain, a GABAR transmembrane domain, or a GABAR intracellular domain and one or more domains from a mGluR subtype 8 (mGluR8) and/or a CaR.

G-protein fusion receptors and constructs encoding same

Protein disulfide isomerase is a major component ofvenom ducts. The invention relates to a protein disulfide isomerase (PDI) fromsnails, a nucleic acid sequence encoding theprotein disulfide isomerase, and to methods for folding disulfide-rich peptides using a protein disulfide isomerase. Oxidative folding of conotoxin precursors, catalyzed by a PDI, was more efficient and decreased the number and concentration of transiently accumulated folding species. The PDI-assisted oxidative folding of conotoxins was also influenced by the propeptide relative to the mature peptide.

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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 present invention is to &mgr;-conopeptides, 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 sodium channels. Thus, the &mgr;-conopeptides or derivatives are useful as neuromuscular blocking agents, local anesthetic agents, analgesic agents and neuroprotective agents. The &mgr;-conopeptides are also useful for treating neuromuscular disorders. The invention is further directed to nucleic acid sequences encoding the &mgr;-conopeptides and encoding propeptides, as well as the propeptides.

Mu-conopeptides

The present invention relates to the different roles inorganic ion receptors have in cellular and body processes. The present invention features: (1) molecules which can modulate one or more inorganic ion receptor activities, preferably the molecule can mimic or block an effect of an extracellular ion on a cell having an inorganic ion receptor, more preferably the extracellular ion is Ca.sup.2+ and the effect is on a cell having a calcium receptor; (2) inorganic ion receptor proteins and fragments thereof, preferably calcium receptor proteins and fragments thereof; (3) nucleic acids encoding inorganic ion receptor proteins and fragments thereof, preferably calcium receptor proteins and fragments thereof; (4) antibodies and fragments thereof, targeted to inorganic ion receptor proteins, preferably calcium receptor protein; and (5) uses of such molecules, proteins, nucleic acids and antibodies.

Calcium receptor-active molecules

Method of screening calcium receptor-active molecules

The present invention features calcium receptor polypeptides and fragments thereof. Uses of a calcium receptor polypeptide include providing a polypeptide having the activity of a calcium receptor polypeptide. Calcium receptor polypeptide fragments can be used, for example, to generate antibodies to a calcium receptor polypeptide.

Growing community of inventors

Salt Lake City, UT, United States of America

James E Garrett