A SYNTHETIC PEPTIDE DERIVED FROM THE SEQUENCE OF A TYPE-I COLLAGEN RECEPTOR INHIBITS TYPE COLLAGEN-MEDIATED PLATELET-AGGREGATION

A synthetic peptide-1, an 18 amino acid residue peptide derived from a hydrophilic domain of a cloned platelet type I collagen receptor, was used to study the role of the receptor on types I and III collagen-in duced platelet aggregation and the release of ATP. The peptide inhibit s the type I, but not the type III, collagen-induced platelet aggregat ion and the release of ATP in a dose-dependent manner. The [I-125]pept ide-1 specifically binds to type I collagen-coated microtiter wells in a dose-dependent manner (with K-d = 10 nM). The binding of [I-125]pep tide-1 can be inhibited by an excess of unlabeled peptide-1 suggesting that the binding is specific. The labeled peptide-1 does not bind to type III collagen-coated microtiter wells, Results from an enzyme-link ed immunosorbent assay show that the peptide reacts with the poly-and monoclonal antibodies raised against the purified platelet type I coll agen receptor (M-r 65 kD). The peptide also inhibits the adhesion of p latelets on type I collagen matrix and rabbit aortic segments in a dos e-dependent manner. These results suggest that the reactive. site of t he platelet receptor for type I collagen resides in this portion of th e molecule.