The synthetic RGDS peptide inhibits the binding of fibrinogen lacking intact alpha chain carboxyterminal sequences to human blood platelets.
The alpha chain 572-574 Arg-Gly-Asp sequence of fibrinogen appears to play only a minor role in platelet aggregation based on the ability of fibrinogen preparations lacking alpha chain carboxyterminal segments to support platelet aggregation, but synthetic Arg-Gly-Asp-Ser (RGDS) peptides are capable of inhibiting platelet aggregation and fibrinogen binding. The present study thus examined the ability of RGDS peptides to inhibit platelet interactions with a plasmic degradation product of fibrinogen (8D-50) that resembles an intermediate fragment X. Gel-filtered, human blood platelets suspended in 0.01 mol/L HEPES-buffered modified Tyrode's solution, pH 7.5, were stimulated with 20 mumol/L adenosine diphosphate and the binding of 125I-labeled 8D-50 or intact fibrinogen (0.01 to 0.6 mg/mL) assessed in the presence of 0 to 117 mumol/L RGDS. The data revealed that RGDS decreased the apparent affinity of 8D-50 and intact fibrinogen for platelets but did not affect the maximum number of binding sites. RGDS thus appears to be a competitive inhibitor not only of intact fibrinogen (Ki = 12 +/- 2 mumol/L) but also of 8D-50 (Ki = 15 +/- 3 mumol/L) (mean +/- SD, n = 3).
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects
D009842:Oligopeptides; D010446:Peptide Fragments; D005340:Fibrinogen; C046617:arginyl-glycyl-aspartyl-serine