FLUOSTATIN-A AND FLUOSTATIN-B, NEW INHIBITORS OF DIPEPTIDYL PEPTIDASE-III, PRODUCED BY STREPTOMYCES SP. TA-3391 - I - TAXONOMY OF PRODUCINGSTRAIN, PRODUCTION, ISOLATION, PHYSICOCHEMICAL PROPERTIES AND BIOLOGICAL PROPERTIES

New inhibitors of dipeptidyl peptidaseIII (EC 3.4.14.4) from human pla centa, designated as fluostatins A and B, were discovered in the ferme ntation broth of a strain isolated in our institute. The strain has be en identified as Streptomyces sp. TA-3391 on the basis of taxonomic st udies. Fluostatins A and B were purified by Diaion HP-20 chromatograph y, ethyl acetate extraction, silica gel chromatography and reverse pha se preparative HPLC. With the synthetic substrate, arginyl-arginine-2- naphthylamide, the IC50 values of fluostatins A and B were 0.44 and 24 .0 mu g/ml, respectively. Fluostatins A and B were slightly inhibitory against other dipeptidyl peptidases. Fluostatin A showed mixed-type ( competitive and noncompeptitive) inhibition was human leucine-enkephal in as a substrate, and the inhibition constant (Ki) was 14.2 mu M.