Yang Shu-Hou, Sun Qi, Xiong Hao, Liu Shi-Yu, Moosavi Behrooz, Yang Wen-Chao, Yang Guang-Fu
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China.
Chem Commun (Camb). 2017 Apr 4;53(28):3952-3955. doi: 10.1039/c7cc00577f.
We report herein the structure-based design and application of a fluorogenic molecular probe (BChE-FP) specific to butyrylcholinesterase (BChE). This probe was rationally designed by mimicking the native substrate and optimized stepwise by manipulating the steric feature and the reactivity of the designed probe targeting the structural difference of the active pockets of BChE and AChE. The refined probe, BChE-FP, exhibits high specificity toward BChE compared to AChE, producing about 275-fold greater fluorescence enhancement upon the catalysis by BChE. Thus, BChE-FP is a specific BChE probe identified by the structure-based design and it can discriminate BChE from AChE. Furthermore, it has been successfully applied for imaging the endogenous BChE in living cells, as well as BChE inhibitor screening and characterization under physiological conditions.
我们在此报告一种针对丁酰胆碱酯酶（BChE）的荧光分子探针（BChE-FP）基于结构的设计与应用。该探针通过模拟天然底物进行合理设计，并通过操纵针对BChE和AChE活性口袋结构差异的设计探针的空间特征和反应性逐步优化。优化后的探针BChE-FP与AChE相比，对BChE表现出高特异性，在BChE催化下产生约275倍更高的荧光增强。因此，BChE-FP是一种通过基于结构的设计鉴定的特异性BChE探针，它可以区分BChE和AChE。此外，它已成功应用于活细胞内源性BChE的成像，以及生理条件下BChE抑制剂的筛选和表征。
