TETRAFIBRICIN, A NOVEL FIBRINOGEN RECEPTOR ANTAGONIST

I. TAXONOMY, FERMENTATION, ISOLATION, CHARACTERIZATION AND BIOLOGICAL ACTIVITIES

Abstract

Tetrafibricin is a novel fibrinogen receptor antagonist produced by Streptomyces neyagawaensis NR0577. It was isolated from the culture broth by Diaion HP-21 adsorption, MeOH extraction, MCI GEL CHP-20P column chromatography, preparative HPLC and Toyopearl HW-40 SF column chromatography. The physico-chemical properties of tetrafibricin indicated that the structure of tetrafibricin is different from the known peptide fibrinogen receptor antagonists and closely related to the polyene macrolide antibiotics. Tetrafibricin strongly inhibited the binding of fibrinogen to its receptors with an IC₅₀ of 46 nM. It also inhibited ADP-, collagen-, and thrombin-induced aggregation of human platelets with IC₅₀s of 5.6, 11.0 and 7.6μM, respectively.