NMR Biochemical Assay for Oxidosqualene Cyclase: Evaluation of Inhibitor Activities on <i>Trypanosoma cruzi</i> and Human Enzymes
作者:Osamu Tani、Yukie Akutsu、Shinji Ito、Takayuki Suzuki、Yukihiro Tateishi、Tomohiko Yamaguchi、Tatsuya Niimi、Ichiji Namatame、Yasunori Chiba、Hitoshi Sakashita、Tomomi Kubota、Tetsuo Yanagi、Shusaku Mizukami、Kenji Hirayama、Koji Furukawa、Kazuhiko Yamasaki
DOI:10.1021/acs.jmedchem.8b00484
日期:2018.6.14
Oxidosqualene cyclase (OSC), a membrane-associated protein, is a key enzyme of sterol biosynthesis. Here we report a novel assay for OSC, involving reaction in aqueous solution, NMR quantification in organic solvent, and factor analysis of spectra. We evaluated one known and three novel inhibitors on OSC of Trypanosoma cruzi, a parasite causative of Chagas disease, and compared their effects on human
氧化角鲨烯环化酶(OSC)是一种膜相关蛋白,是固醇生物合成的关键酶。在这里,我们报告了一种新颖的OSC分析方法,包括在水溶液中的反应,在有机溶剂中的NMR定量以及光谱的因子分析。我们评估了锥虫锥虫(一种恰加斯氏病的病原体)对OSC的已知抑制剂和三种新型抑制剂,并比较了它们对人OSC的选择性影响。其中,一种新型抑制剂显示出显着的杀虫活性。