Inhibition of von Willebrand factor binding to platelets by two recognition site peptides: the pentadecapeptide of the carboxy terminus of the fibrinogen gamma chain and the tetrapeptide arg-gly-asp-ser.
When platelets are stimulated by thrombin or ADP, von Willebrand factor (vWf) binds to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa). Two recognition sites for vWf binding have been identified on the GPIIb/IIIa. One is a tetrapeptide, arg-gly-asp-ser (RGDS), and the second is a dodecapeptide with the sequence HHLGGAKQAGDV. We used these purified peptides to analyze the recognition specificities for the platelet binding of vWf. The RGDS and the pentadecapeptide totally inhibited 125I-vWf in a dose-dependent manner. The IC50 was 8 microM for the RGDS and 40 microM for the pentadecapeptide. These results indicate that the RGDS binds with higher affinity to a vWf binding site on GPIIb/IIIa than does the pentadecapeptide site. When the two peptides were incubated together, they augmented the inhibition of vWf binding. These data support the evidence that the GPIIb/IIIa has two distinct binding sites for vWf binding. The RGDS site appears to have a higher affinity for the vWf binding site than does the pentadecapeptide site.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001665:Binding Sites; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000032:analysis; D013917:Thrombin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism
D009842:Oligopeptides; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D014841:von Willebrand Factor; D000244:Adenosine Diphosphate; D005340:Fibrinogen; C046617:arginyl-glycyl-aspartyl-serine; D013917:Thrombin