Development of novel compound of function selective labeling reagent for proteins and its systematic use

我试图开发一种新的设计这类酶的抑制剂的方法，例如一种神经氨酸酶霍乱弧菌神经氨酸酶(VCNA)，其晶体结构于1994年被报道，最有效的抑制剂在1971年被报道。因此，通过对霍乱弧菌神经氨酸酶关键氨基酸残基的机理标记信息、基于标记信息的聚焦文库骨架的设计、聚焦文库的筛选和基于洗涤剂的杂乱抑制物筛选，开发了霍乱弧菌神经氨酸酶的有效抑制物，以获得病毒、细菌和哺乳动物神经氨酸酶的有效和选择性抑制物(Ki=73 nM)。

I have tried to develop a novel method of inhibitor design of such enzymes exemplified to a neuraminidase Vibrio cholerae neuraminidase (VCNA) of which crystal structure was reported in 1994 and most potent inhibitor was reported in 1971. As a result, a potent inhibitor for Vibrio cholerae neuramnidase was developed using mechanism-based labeling information of key amino acid residues, design of a skeleton of focused library based on labeling information, screening of the focused library, and elimination of promiscuous inhibitor by detergent-based assay to afford potent (Ki=73nM) and selective inhibitor among viral, bacterial, and mammal neuraminidases.