Peptide inhibitors of inflammation mediated by selectins

US6528487B1 · kind B1 · 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

Key dates

• Filing date: Oct 12, 1993
• Grant date: Mar 4, 2003
• Expiry date: Oct 12, 2013

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P29/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Peptides derived from three regions of the lectin domain of GMP-140 and the related selectins, ELAM-1 and the lymphocyte homing receptor, have seen found to inhibit neutrophil adhesion to GMP-140. These and additional peptides have been synthesized, having as their core region portions of the 56-60 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 5 to 1500 &mgr;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.