THE SYNTHETIC RGDS PEPTIDE INHIBITS THE BINDING OF FIBRINOGEN LACKING INTACT ALPHA-CHAIN CARBOXYTERMINAL SEQUENCES TO HUMAN-BLOOD PLATELETS

  • 1 March 1987
    • journal article
    • research article
    • Vol. 69  (3) , 950-952
Abstract
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 .mu.mol/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 .mu.mol/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 .mu.mol/L) but also of 8D-50 (Ki = 15 .+-. 3 .mu.mol/L) (mean .+-. SD, n = 3).