Synthetic RGDS-Containing Peptides of von Willebrand Factor Inhibit Platelet Adhesion to Collagen

Summary

We compared the effect of a synthetic dodecapeptide of residues 400-411 of the Γ chain of fibrinogen (Γ Fg 400-411) and of three synthetic peptides (15 to 18 aminoacids), of human von Willebrand Factor (vWF), containing the 1744-1747 Arg-Gly-Asp-Ser (RGDS) sequence, upon platelet adhesion to collagen in flowing blood. Both types of peptides are known to inhibit the binding of adhesive proteins to platelet membrane glycoprotein Ilb/IIIa (GPIIb/IIIa). Collagen was coated onto plastic cover slips and exposed in parallel-plate perfusion chambers to reconstituted human blood at various shear rates for 5 min at 37 °C. At a shear rate of 2,600 s⁻¹, RGDS peptides inhibited platelet adhesion to collagen in a dose-dependent manner and appeared to be more potent inhibitors than the Γ Fg 400-411 on a molar basis. No synergetic effect between RGDS and Γ Fg 400-411 peptides was observed. These results suggest that the RGDS peptides affect adhesion by inhibiting the GPIIb/IIIa-vWF interaction and confirm the involvement of this platelet receptor in vWF-mediated platelet adhesion to collagen at high shear rate.

• References

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