TMC-2A, TMC-2B AND TMC-2C, NOVEL DIPEPTIDYL PEPTIDASE-IV INHIBITORS PRODUCED BY ASPERGILLUS-ORYZAE A374 .1. TAXONOMY OF PRODUCING STRAIN, FERMENTATION, AND BIOCHEMICAL-PROPERTIES

TMC-2A (1), -2B (2) and -2C (3), novel dipeptidyl peptidase IV (DPIV) inhibitors, were isolated from the fermentation broth of Aspergillus o ryzae A374. TMC-ZA, -2B and -2C inhibited rat kidney DPIV with IC50 va lue of 8.1 mu M, 17 mu M, and 20 mu M, respectively, as well as human DPIV prepared from mononuclear cells and adenocarcinoma cells. TMC-2 c ompounds inhibited only DPIV among the proteases tested, indicating th eir high selectivity for DPIV. The kinetic analyses revealed that TMC- 2A was an uncompetitive inhibitor. Taxonomy and fermentation of the pr oducing strain are also described.