High-affinity response-selective C-terminal analogs of C5a anaphylatoxin

US6465614B1 · kind B1 · utility

Assignee

• BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA · US

Inventors

• Sam D. Sanderson · Omaha, US
• Simon A. Sherman · Omaha, US
• Leonid Kirnarsky · Omaha, US
• Stephen Maxwell Taylor · Ipswich, AU

Key dates

• Filing date: Jul 21, 1999
• Grant date: Oct 15, 2002
• Expiry date: Jul 21, 2019

Classification

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

Abstract

High-affinity response-selective C-terminal analogs of C5a anaphylatoxin are provided. Whereas natural C5a has considerable flexibility in the C-terminal region, the analogs of the invention possess a backbone conformation which is constrained at the C-terminus to a &bgr;-turn. The stabilized &bgr;-turn confers a marked increase in potency of the analogs; the particular &bgr;-turn motif further confers the capability to selectively elicit certain biological responses associated with C5a. Exemplary compounds of the invention are decapeptide analogs of the formula: A1-Ser-Phe-Lys-A2-A3-A4-A5-A6-A7, with the constrained &bgr;-turn being localized in the region of A4-A7.