Nonaka N, Asai Y, Nishio M, Takahashi K, Okuda T, Tanaka S, Sugita T, Ohnuki T, Komatsubara S
Lead Generation Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
J Antibiot (Tokyo). 1997 Aug;50(8):646-52. doi: 10.7164/antibiotics.50.646.
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.
新型二肽基肽酶IV（DPIV）抑制剂TMC-2A（1）、-2B（2）和-2C（3）是从米曲霉A374的发酵液中分离得到的。TMC-2A、-2B和-2C对大鼠肾脏DPIV的抑制中浓度（IC50）分别为8.1微摩尔、17微摩尔和20微摩尔，对从单核细胞和腺癌细胞制备的人DPIV也有抑制作用。在测试的蛋白酶中，TMC-2类化合物仅抑制DPIV，表明它们对DPIV具有高度选择性。动力学分析表明，TMC-2A是一种非竞争性抑制剂。文中还描述了产生菌的分类学和发酵情况。
