Catalytic self-screening of cholinesterase substrates from a dynamic combinatorial thioester library

被引:79
作者
Larsson, R [1 ]
Pei, ZC [1 ]
Ramström, O [1 ]
机构
[1] Royal Inst Technol, Dept Chem, S-10044 Stockholm, Sweden
关键词
combinatorial chemistry; enzyme catalysis hydrolysis; proteomics; transesterification;
D O I
10.1002/anie.200454165
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Simply the best: Dynamic combinatorial chemistry coupled to enzyme catalysis was used to identify enzyme substrates in a library constructed from a series of thioesters and thiols by transesterification. The library was directly coupled to the catalytic action of acetylcholinesterase, which selectively hydrolyzed the best substrate candidates (see schematic representation). The process allowed rapid identification of discrete substrates.
引用
收藏
页码:3716 / 3718
页数:3
相关论文
共 25 条
[1]  
[Anonymous], 1996, ANGEW CHEM, V108, P1987
[2]   Generation of Bis-cationic heterocyclic inhibitors of Bacillus subtilis HPr kinase/phosphatase from a ditopic dynamic combinatorial library [J].
Bunyapaiboonsri, T ;
Ramström, H ;
Ramström, O ;
Haiech, J ;
Lehn, JM .
JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (26) :5803-5811
[3]  
Bunyapaiboonsri T, 2001, CHEMBIOCHEM, V2, P438
[4]   Amplification of screening sensitivity through selective destruction: Theory and screening of a library of carbonic anhydrase inhibitors [J].
Cheeseman, JD ;
Corbett, AD ;
Shu, R ;
Croteau, J ;
Gleason, JL ;
Kazlauskas, RJ .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (20) :5692-5701
[5]   Structure-based alignment and comparative molecular field analysis of acetylcholinesterase inhibitors [J].
Cho, SJ ;
Garsia, MLS ;
Bier, J ;
Tropsha, A .
JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (26) :5064-5071
[6]   Molecular evolution: dynamic combinatorial libraries, autocatalytic networks and the quest for molecular function [J].
Cousins, GRL ;
Poulsen, SA ;
Sanders, JKM .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2000, 4 (03) :270-279
[7]   Use of molecular recognition to drive chemical evolution .1. Controlling the composition of an equilibrating mixture of simple arginine receptors [J].
Eliseev, AV ;
Nelen, MI .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (05) :1147-1148
[8]   In situ assembly of enzyme inhibitors using extended tethering [J].
Erlanson, DA ;
Lam, JW ;
Wiesmann, C ;
Luong, TN ;
Simmons, RL ;
DeLano, WL ;
Choong, IC ;
Burdett, MT ;
Flanagan, WM ;
Lee, D ;
Gordon, EM ;
O'Brien, T .
NATURE BIOTECHNOLOGY, 2003, 21 (03) :308-314
[9]  
GANESAN A, 1998, ANGEW CHEM, V110, P2989
[10]   Self-assembly of a circular double helicate [J].
Hasenknopf, B ;
Lehn, JM ;
Kneisel, BO ;
Baum, G ;
Fenske, D .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1996, 35 (16) :1838-1840