Peptide inhibitors of inflammation mediated by selectins

US6111065A · kind A · utility

Assignees

• Centocor, Inc. · US
• The Board of Regents of the University of Oklahoma · US

Inventors

• George Heavner · Malvern, US
• Rodger P. McEver · Oklahoma City, US
• Jian-Guo Geng · Portage, US
• Douglas James Riexinger · Flemington, US
• Marian Kruszynski · West Chester, US
• Leon A. Epps · Baltimore, US
• Miljenko Mervic · King of Prussia, US

Key dates

• Filing date: Apr 26, 1994
• Grant date: Aug 29, 2000
• Expiry date: Apr 26, 2014

Classification

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

Abstract

Peptides derived from three regions of the lectin domain of GMP-140 (P-selectin) and the related selectins, ELAM-1 (E-selectin) and the lymphocyte homing receptor (L-selectin), have been found to inhibit neutrophil adhesion to GMP-140. These and additional peptides have been synthesized, having as their core region portions of the 74-76 amino acid sequence of GMP-140, with residue 1 defined as the N-terminus of the mature protein after the cleavage of the signal peptide. Examples demonstrate the inhibition of the binding of neutrophils to GMP-140 of peptides in concentrations ranging from 30 to 1500 .mu.mol. It has been found that alterations within the core sequence, as well as N-terminal and C-terminal flanking regions, do not result in loss of biological activity. The peptides are useful as diagnostics and, in combination with a suitable pharmaceutical carrier, for clinical applications in the modulation or inhibition of coagulation processes or inflammatory processes.