Inventors:
George A. Heavner - Flemington NJ
Rodger P. McEver - Oklahoma City OK
Jian-Guo Geng - Oklahoma City OK
Douglas J. Riexinger - Flemington NJ
Marian Kruszynski - West Chester PA
Leon A. Epps - Baltimore MD
Miljenko Mervic - King of Prussia PA
Assignee:
Centocor, Inc. - Malvern PA
The Board of Regents of the University of Oklahoma - Norman OK
International Classification:
C07K 1400
C07K 704
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.
