GLYCOPROTEIN IB-ALPHA PEPTIDES INHIBIT THROMBIN AND SFLLRN-INDUCED PLATELET-AGGREGATION

The platelet glycoprotein Ib alpha (GPIb alpha) receptor contains a hi gh-affinity binding site for thrombin that, when occupied, augments pl atelet activation and aggregation in part via the 7-transmembrane doma in receptor (7-TMDR). We have constructed a series of peptides derived from GPIb alpha that encompass the amino acid sequence F216-T240. We have studied the effect(s) of these peptides on platelet aggregation i nduced by thrombin or by the 7-TMDR peptide SFLLRN. Twenty-four peptid es were synthesized from the peptide sequence F216-T240. Several of th e peptides derived from the sequence W219-V227 of GPIb alpha inhibited platelet aggregation, which was primarily dependent on the presence o f the amino acid sequence A224-N226 (AEN). These data suggest that a r egion within the GPIb alpha chain modulates the platelet aggregation i nduced by alpha-thrombin. These GPIb alpha peptides did not interfere with platelet aggregation induced by other agonists-for example, colla gen, ristocetin, calcium ionophore, or botrocetin-which indicates that these GPIb alpha peptide-platelet interaction(s) are specific. Our st udies provide another potential mechanism for modulating platelet acti vation and aggregation via synthetic and natural peptides.