An NMR Biochemical Assay for Fragment-Based Drug Discovery: Evaluation of an Inhibitor Activity on Spermidine Synthase of Trypanosoma cruzi

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• 作者：Kazuhiko Yamasaki ; Osamu Tani ; Yukihiro Tateishi ; Eiki Tanabe ; Ichiji Namatame ; Tatsuya Niimi ; Koji Furukawa ; Hitoshi Sakashita
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：March 10, 2016
• 年：2016
• 卷：59
• 期：5
• 页码：2261-2266
• 全文大小：342K
• ISSN：1520-4804

文摘

Although NMR in fragment-based drug discovery is utilized almost exclusively to evaluate physical binding between molecules, it should be also a powerful tool for biochemical assay, evaluating inhibitory effect of compounds on enzymatic activity. Time-dependent spectral change in real-time monitoring or inhibitor concentration-dependent spectral change after constant-time reaction was processed by factor analysis, by which reaction rate or IC₅₀ value was obtained. Applications to spermidine synthase of Trypanosoma cruzi, which causes Chagas disease, are described.