The role of the RGD peptides and the gamma chain peptide of fibrinogen on fibrinogen binding to activated platelets.
The interaction of fibrinogen with platelet membrane glycoprotein (GP) IIb/IIIa complex is inhibited by the RGD peptides and the peptides corresponding to a sequence unique to fibrinogen in the carboxyl-terminal domain of the gamma chain. The present study was designed to examine the effects of these synthetic peptides on fibrinogen binding to thrombin-activated platelets. The order of potency of these peptides was as follows: RGDS = RGDF > GQQHHLGGAKQAGDV (G15). The RGES peptide had no inhibitory activity. The inhibitory effects of the peptides were synergistic when fibrinogen binding was measured in the mixture of the RGD peptide and the gamma chain peptide. By contrast, the inhibitory effect was additive when the binding was measured in the presence of the RGDS peptide and the RGDF peptide. Thrombin-induced platelet aggregation was also inhibited by these synthetic peptides. The order of potency was the same as that of the inhibition binding assay. These results provide evidence that the RGD sequences present at two different sites in the alpha chain and the gamma chain sequence inhibit fibrinogen binding to the GPIIb/IIIa complex, are mutually exclusive, and are in close spatial proximity in the folded molecule. We conclude that the presence of the RGD sequence and the gamma chain sequence involved in fibrinogen binding domains increases the affinity of fibrinogen to activated platelets.
Mohri
H
H
First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Ohkubo
T
T
D000595:Amino Acid Sequence; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism
D009842:Oligopeptides; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen; C046617:arginyl-glycyl-aspartyl-serine