Inhibition of platelet-von Willebrand factor binding to platelets by
adhesion site peptides
RI Parker and HR Gralnick
Clinical Pathology Department, Clinical Center, National Institutes of
Health, Bethesda, MD 20892.
Synthetic peptides containing the adhesion site recognition sequences
present on the A alpha and gamma 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 gamma-chain (IC50 10.6 mumol/L for the RGDS tetrapeptide v 44.9
mumol/L for the gamma-chain pentadecapeptide). No apparent synergy in the
inhibition of plasma-vWf binding was noted when the RGDS and gamma-chain
peptides were used together (IC50 15.2 mumol/L). In contrast, the
gamma-chain peptide was significantly more inhibitory than was the RGDS
tetrapeptide on the binding of platelet-vWf to platelets (IC50 1.4 mumol/L
for the gamma-chain pentadecapeptide v 4.5 mumol/L for the RGDS
tetrapeptide, P less than .05), and there was significant synergy in the
inhibition of platelet-vWf binding noted when the gamma-chain and RGDS
peptides were used together (IC50 0.04 mumol/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 gamma-chain
recognition sites. In contrast to the results with plasma-vWf binding, the
gamma-chain recognition site appears to be more important than the RGDS
recognition site in platelet- vWf binding to platelets.
Volume 74,
Issue 4,
pp. 1226-1230,
09/01/1989
Copyright © 1989 by The American Society of Hematology
