TMC-2A, -2B and -2C, novel dipeptidyl peptidase IV inhibitors produced by Aspergillus oryzae A374. I. Taxonomy of producing strain, fermentation, and biochemical properties

J Antibiot (Tokyo). 1997 Aug;50(8):646-52. doi: 10.7164/antibiotics.50.646.

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 IC50 value of 8.1 microM, 17 microM, and 20 microM, 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.

MeSH terms

  • Animals
  • Aspergillus oryzae
  • Cells, Cultured
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors*
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology*
  • Fermentation
  • Humans
  • Indoles / isolation & purification*
  • Indoles / pharmacology*
  • Isoquinolines / isolation & purification*
  • Isoquinolines / pharmacology*
  • Kidney / drug effects
  • Kidney / enzymology
  • Male
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Enzyme Inhibitors
  • Indoles
  • Isoquinolines
  • TMC 2A
  • TMC 2B
  • TMC 2C
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases