Urocortin peptides, nucleic acid encoding same methods for using same

US6214797A · kind A · utility

Assignee

• Salk Institute for Biological Studies · US

Inventors

• Wylie W. Vale, Jr. · Village of La Jolla, US
• Joan Vaughan · San Diego, US
• Cynthia J. Donaldson · San Diego, US
• Kathy A. Lewis · San Diego, US
• Paul Sawchenko · Encinitas, US
• Jean E. F. Rivier · Village of La Jolla, US
• Marilyn H. Perrin · Village of La Jolla, US

Key dates

• Filing date: Dec 10, 1997
• Grant date: Apr 10, 2001
• Expiry date: Dec 10, 2017

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Urocortin (Ucn) is a native mammalian peptide generally related to Urotensin I and Corticotropin Releasing Factor (CRF). Human Ucn has the formula: Asp-Asn-Pro-Ser-Leu-Ser-Ile-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Thr-Leu-Leu-Gl u-Leu-Ala-Arg-Thr-Gln-Ser-Gln-Arg-Glu-Arg-Ala-Glu-Gln-Asn-Arg-Ile-Ile-Phe-A sp-Ser-Val-NH.sub.2 (SEQ ID NO:15). Rat-derived Ucn is identical but for 2 substitutions, Asp.sup.2 for Asn.sup.2 and Pro.sup.4 for Ser.sup.4. Ucn or analogs thereof or pharmaceutically acceptable salts can be administered to humans and other mammals to achieve substantial elevation of ACTH, .beta.-endorphin, .beta.-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone. They can also be used to lower blood pressure over an extended period of time, as stimulants to elevate mood and to improve memory and learning performance, as well as diagnostically. Shortened fragments may be administered to release endogenous CRF and/or Ucn in the brain and peripherally. Ucn antagonists can be used to block the action of Ucn and/or CRF, as can antibodies to Ucn. Labelled Ucn agonists and antagonists can be used in drug screening assays along with CRF receptors; they may also be …