化学
生物信息学
氟-19核磁共振
酶
片段(逻辑)
活动站点
蛋氨酸
生物化学
立体化学
核磁共振波谱
氨基酸
基因
计算机科学
程序设计语言
作者
Kazuyoshi Ikeda,Yuichiro Kezuka,Takamasa Nonaka,Tomoki Yonezawa,Masatoshi Osawa,Etsuko Katoh
标识
DOI:10.1021/acs.jmedchem.1c00766
摘要
Fragment-based screening using 19F NMR (19F-FS) is an efficient method for exploring seed and lead compounds for drug discovery. Here, we demonstrate the utility and merits of using 19F-FS for methionine γ-lyase-binding fragments, together with a 19F NMR-based competition and mutation assay, as well as enzymatic and in silico methods. 19F NMR-based assays provided useful information on binding between 19F-FS hit fragments and target proteins. Although the 19F-FS and enzymatic assay were weakly correlated, they show that the 19F-FS hit fragments contained compounds with inhibitory activity. Furthermore, we found that in silico calculations partially account for the differences in activity levels between the 19F-FS hits as per NMR analysis. A comprehensive approach combining the 19F-FS and other methods not only identified fragment hits but also distinguished structural differences in chemical groups with diverse activity levels.
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