TMC-2A, -2B and -2C, Novel Dipeptidyl Peptidase IV Inhibitors Produced by Aspergillus oryzae A374

I. Taxonomy of Producing Strain, Fermentation, and Biochemical Properties

Abstract

TMC-2A (1), -2B (2) and -2C (3), novel dipeptidyl peptidase IV (DPIV) inhibitors, were isolated from the fermentation broth of Aspergillus oryzae A374. TMC-2A, -2B and -2C inhibited rat kidney DPIV with 1C₅₀ value of 8.1 μM, 17μ, and 20μ, respectively, as well as human DPIV prepared from mononuclear cells and adenocarcinoma cells. TMC-2 compounds inhibited only DPIV among the proteases tested, indicating their high selectivity for DPIV. The kinetic analyses revealed that TMC-2A was an uncompetitive inhibitor. Taxonomy and fermentation of the producing strain are also described.