Inhibition of Platelet-von Willebrand Factor Binding to Platelets by Adhesion Site Peptides

• Published in: Blood 1989-09, Vol.74 (4), p.1226-1230
• Main Authors: Parker, Robert I., Gralnick, Harvey R.
• Format: Article
• Language: English
• Subjects: Binding, Competitive; Biological and medical sciences; Blood coagulation. Blood cells; Coagulation factors; Fundamental and applied biological sciences. Psychology; Humans; Molecular and cellular biology; Oligopeptides - pharmacology; Platelet Adhesiveness - drug effects; Platelet Aggregation Inhibitors - pharmacology; Platelet Membrane Glycoproteins; Receptors, Cell Surface - drug effects; Thrombin; von Willebrand Factor - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V74.4.1226.1226

Synthetic peptides containing the adhesion site recognition sequences present on the Aα and γ chains of fibrinogen were studied for their effect on the binding of endogenous platelet-von Willebrand factor (vWF) and exogenous plasma-vWf to thrombin-stimulated platelets. In agreement with previously reported data, the tetrapeptide consisting of the RGDS sequence was a more potent inhibitor of plasma-vWf binding to platelets than was the pentadecapeptide of the carboxy terminus of the fibrinogen γ-chain (IC50 10.6 μmol/L for the RGDS tetrapeptide v 44.9 μmol/L for the γ-chain pentadecapeptide). No apparent synergy in the inhibition of plasma-vWf binding was noted when the RGDS and γ-chain peptides were used together (IC50 15.2 μmol/L). In contrast, the γ-chain peptide was significantly more inhibitory than was the RGDS tetrapepetide on the binding of platelet-vWf to platelets (IC50 1.4 μmol/L for the γ-chain pentadecapeptide v 4.5 μmol/L for the RGDS tetrapeptide, P < .05), and there was significant synergy in the inhibition of platelet-vWf binding noted when the γ-chain and RGDS peptides were used together (IC50 0.04 μmol/L). These results indicate that the binding of platelet-vWf to its receptor on the platelet glycoprotein IIb/IIIa complex involves both the RGDS and γ-chain recognition sites. In contrast to the results with plasma-vWf binding, the γ-chain recognition site appears to be more important than the RGDS recognition site in platelet-vWf binding to platelets.