In our screening program for fibrinogen receptor antagonists of microbial origin, we isolated a novel fibrinogen receptor antagonist, tetrafibricin, from the culture broth of Streptomyces neyagawaensis NR0577. Tetrafibricin was purified by Diaion HP-21 adsorption, MeOH extraction, Diaion CHP-20P column chromatography, prep-HPLC (C_<18>), Diaion CHP-20P and Toyopearl HW-40 SF column chromatography. The molecular formula was determined to be C_<41>H_<67>NO_<13> by HR FAB-MS and NMR data. The structure of tetrafibricin was determined to be 1 by various 2D-NMR experiments on tetrafibricin and N-acetyl-dihydrotetrafibricin methyl ester (4). Tetrafibricin strongly inhibited the binding of fibrinogen to its receptors in the GPIIb/IIIa solid phase assay with an IC_<50>of 46 nM and it also inhibited ADP-, collagenor thrombin-induced aggregation of human platelets with IC_<50>s of 5.6, 11.0, 7.6μM, respectively.
