Cystine knot peptides binding to alpha IIb beta 3 integrins and methods of use

US8778888B2 · kind B2 · utility

Assignee

• The Board of Trustees of the Leland Stanford Junior University · US

Inventors

• Jennifer R. Cochran · Stanford, US
• Adam P. Silverman · South San Francisco, US
• Mihalis Kariolis · South San Francisco, US

Key dates

• Filing date: Nov 2, 2010
• Grant date: Jul 15, 2014
• Expiry date: Jun 30, 2032

Classification

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

Abstract

Disclosed are peptides having a cystine knot structural motif and comprising a sequence engineered for specificity against αIIbβ3 integrin, found on platelets, and a method of using the same in anti-thrombotic therapies. The present peptides utilize a cystine knot scaffold derived from modified agouti-related protein or agatoxin, An alternate library screening strategy was used to isolate variants of peptides that selectively bound to αIIbβ3 integrin or to both αIIbβ3 and αVβ3 integrins. Unique consensus sequences were identified within the identified peptides suggesting alternative molecular recognition events that dictate different integrin binding specificities. In addition, the engineered peptides prevented human platelet aggregation in a plasma-based assay and showed high binding affinity for αIIbβ3 integrin.