University of Utah Research Foundation

Cognetix, Inc.

Siqin Luo

Baldomero M Olivera

J Michael McIntosh

Doju Yoshikami

G Edward Cartier

The present invention relates to the use of &#x3b1;-conotoxin peptides having the general formula Xaa-Xaa-Cys-Cys-Xaa-Xaa-Pro-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO:1) for treating disorders regulated at neuronal nicotinic acetylcholine receptors. Such disorders include, but are not limited to, cardiovascular disorders, gastric motility disorders, urinary incontinence, nicotine addiction, mood disorders (such as bipolar disorder, unipolar depression, dysthymia and seasonal effective disorder) and small cell lung carcinoma, as well as the localization of small cell lung carcinoma. In this formula, Xaais des-Xaa, Tyr, mono-iodo-Tyr or di-iodo-Tyr, Xaais any amino acid, Xaais any amino acid, Xaais any amino acid, Xaais any amino acid; Xaais any amino acid, Xaais any amino acid, Xaais any amino acid, Xaais des-Xaaor any amino acid, Xaais des-Xaaor any amino acid, Xaais des-Xaaor any amino acid and Xaais des-Xaaor any amino acid. Disulfide linkages exist between the first and third cysteines and the second and fourth cysteines. Pro may be replaced with hydroxy-Pro. The C-terminus may contain a hydroxyl or an amide group, preferably an amide group.

Uses of &#x3b1;-conotoxin peptides

Uses of &agr;-conotoxin peptides

This invention relates to relatively short peptides about 14-17 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 two cyclizing disulfide linkages. More specifically, the present invention is directed to conopeptides having the general formula: Gly-Cys-Cys-Ser-Tyr-Xaa.sub.1 -Xaa.sub.1 -Cys-Phe-Ala-Thr-Asn-Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.4 -Cys (SEQ ID NO: 1), wherein Xaa.sub.1 is Pro or Hyp (trans-4-hydroxy-Pro), Xaa.sub.2 is Ser, Pro or Hyp, Xaa.sub.3 is Gly or Asp and Xaa.sub.4 is a Tyr or des- Xaa.sub.4. The disulfide bridges are between the first and third between the second fourth cysteine residues. The C-terminal end is preferably amidated. The invention further relates to the specific peptides AuIA: Gly-Cys-Cys-Ser-Tyr-Pro-Pro-Cys-Phe-Ala-Thr-Asn-Ser-Asp-Tyr-Cys (SEQ ID NO:2); AuIB: Gly-Cys-Cys-Ser-Tyr-Pro-Pro-Cys-Phe-Ala-Thr-Asn-Pro-Asp-Cys (SEQ ID NO:3); and AuIC: Gly-Cys-Cys-Ser-Tyr-Pro-Pro-Cys-Phe-Ala-Thr-Asn-Ser-Gly-Tyr-Cys (SEQ ID NO:4). The invention also includes pharmaceutically acceptable salts of the conopeptides.

Conopeptides AuIA, AuIB and AuIC

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Salt Lake City, UT, United States of America

Siqin Luo