Citation

Kawasaki T, Sakai Y, Taniuchi Y, Sato K, Maruyama K, Shimizu M, Kaku S, Yano S, Inagaki O, Tomioka K, Yanagisawa I, Takenaka T. Biochimie 1996; 78(4): 245-252.

Affiliation

Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co Ltd, Ibaraki, Japan.

Copyright

(Copyright © 1996, Elsevier Publishing)

DOI

unavailable

PMID

8874799

Abstract

We biochemically characterized a new disintegrin, flavostatin, isolated from Trimeresurus flavoviridis venom. Flavostatin inhibited ADP-, collagen-, and thrombin receptor agonist peptide-induced platelet aggregation in human platelet-rich plasma (IC50 range: 59 to 111 nM) and blocked the binding of biotinylated human fibrinogen to purified GPIIb/IIIa with an inhibitory potency 31,000-fold higher than that of Arg-Gly-Asp-Ser (RGDS). Flavostatin strongly inhibited high-shear-stress-induced platelet aggregation in platelet-rich plasma (PRP) with an IC50 value of 188 nM. Fluorescein isothiocyanate (FITC)-conjugated flavostatin saturably bound to unstimulated and ADP-stimulated washed platelets with high affinity (Kd values: 38 and 21 nM, respectively); the corresponding number of binding sites was 86460 and 79192 per platelet. In competition experiments with several glycoprotein IIb/IIIa antagonists, the binding of FITC-conjugated flavostatin to platelets was completely inhibited by ReoPro, triflavin, TP9201, MK383 and GR144053, but not by YM207, YM337 and B6A3.

Language: en