A Practical and High-Affinity Fluorescent Probe for Butyrylcholinesterase:A Good Strategy for Binding Affinity Characterization  

作　　者：Lei Wang Chenxi Du Hui Liu Weimin Qiu Xin Lu Yanyu Hu Yueqing Li Tianyu Sun Yao Chen Haopeng Sun 

机构地区：[1]School of Pharmacy,China Pharmaceutical University,Nanjing,Jiangsu 211198,China [2]Department of Natural Medicinal Chemistry,China Pharmaceutical University,Nanjing,Jiangsu 211198,China [3]School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,Jiangsu 210023,China

出　　处：《Chinese Journal of Chemistry》2022年第11期1285-1292,I0002,共9页中国化学（英文版）

基　　金：We gratefully thank the support from the grants of the National Natural Science Foundation of China(Nos.81872728 and 82173652);the Natural Science Foundation of Jiangsu Province(No.BK20191411)。

摘　　要：Butyrylcholinesterase(BChE)is regarded as a promising target for the treatment of Alzheimer's disease(AD),as its level significantly increases along with the progress of this disease.Therefore,the development of potent and high-affinity small-molecule BChE inhibi-tors may be a new strategy for the discovery of anti-AD drugs.However,the current Ellman's method is unable to evaluate the affinity of compounds with BChE,and has a few deficiencies in drug development.Herein,the first small-molecule fluorescence polarization(FP)probes for BChE were rationally designed based on a high affinity inhibitor.Studies indicated that probe F6 exhibited satisfactory fluorescence intensity and suitable fluorescent properties that were compatible with the filters in the FP system.Meanwhile,probe F6 exhibited potent binding affinity to BChE.It is feasible to be applied in detecting the affinity of non-fluorescent compounds to BChE,which lays a solid foundation for the development of small-molecule BChE inhibitors.At the same time,it also can be applied as a val-uable chemical tool for better understanding the molecular biological mechanism of BChE.

关 键 词：BUTYRYLCHOLINESTERASE Alzheimer's disease Fluorescent probes INHIBITORS High-throughput screening 

分 类 号：O62[理学—有机化学]