Tetrafibricin has a high selectivity for GPIIb/IIIa: comparison of the effects of tetrafibricin and RGDS on GPIIb/IIIa and the vitronectin receptor.
The specificity of tetrafibricin was examined by comparing its activities on GPIIb/IIIa and on the vitronectin receptor (alpha v beta 3) with those of Arg-Gly-Asp-Ser (RGDS) on the same receptors. Tetrafibricin, which inhibited fibrinogen-GPIIb/IIIa binding 10 times more potently than RGDS, was three orders of magnitude less potent compared to RGDS on the inhibition of fibrinogen binding to alpha v beta 3. Furthermore, tetrafibricin potently inhibited platelet adhesion to both fibrinogen and von Willebrand factor. Whereas, there was no significant inhibition observed in the GPIIb/IIIa-independent cellular adhesions. These results suggest that tetrafibricin is highly selective for GPIIb/IIIa.
Satoh
T
T
Nippon Roche Research Center, Kanagawa, Japan.
Kouns
W C
WC
Yamashita
Y
Y
Kamiyama
T
T
Steiner
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001011:Aorta; D001792:Blood Platelets / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005340:Fibrinogen / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D007700:Kinetics; D018942:Macrolides; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D016024:Receptors, Cytoadhesin / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D019030:Receptors, Vitronectin; D019096:Vitronectin; D014841:von Willebrand Factor / Q000378:metabolism
D000900:Anti-Bacterial Agents; D006023:Glycoproteins; D016023:Integrins; D018942:Macrolides; D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D019096:Vitronectin; D014841:von Willebrand Factor; C082780:tetrafibricin; D005340:Fibrinogen; C046617:arginyl-glycyl-aspartyl-serine