Conformationally constrained backbone cyclized peptide analogs

US5874529A · kind A · utility

Assignees

• Peptor Ltd. · IL
• YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD. · IL

Inventors

• Chaim Gilon · Jerusalem, IL
• Doron Eren · Rehovot, IL
• Irina Zeltser · Jerusalem, IL
• Alon Seri-Levy · Jerusalem, IL
• Gal Bitan · Jerusalem, IL
• Dan Muller · Jerusalem, IL

Key dates

• Filing date: Dec 5, 1996
• Grant date: Feb 23, 1999
• Expiry date: Dec 5, 2016

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Novel backbone cyclized peptide analogs are formed by means of bridging groups attached via the alpha nitrogens of amino acid derivatives to provide novel non-peptidic linkages. Novel building units disclosed are N.sup..alpha. (.omega.-functionalized)amino acids constructed to include a spacer and a terminal functional group. One or more of these N.sup..alpha. (.omega.-functionalized) amino acids are incorporated into a peptide sequence, preferably during solid phase peptide synthesis. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect either backbone-to-backbone or backbone-to-side chain cyclizations. The invention is exemplified by backbone cyclized bradykinin antagonists having biological activity. Further embodiments of the invention are somatostatin analogs having one or two ring structures involving backbone cyclization.