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Dynamic Deconvolution of a Pre‐Equilibrated Dynamic Combinatorial Library of Acetylcholinesterase Inhibitors
Author(s) -
Bunyapaiboonsri Taridaporn,
Ramström Olof,
Lohmann Sophie,
Lehn JeanMarie,
Peng Ling,
Goeldner Maurice
Publication year - 2001
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/1439-7633(20010601)2:6<438::aid-cbic438>3.0.co;2-j
Subject(s) - hydrazide , acetylcholinesterase , combinatorial chemistry , chemistry , torpedo , pyridinium , deconvolution , cationic polymerization , stereochemistry , computer science , biochemistry , algorithm , organic chemistry , enzyme , acetylcholine receptor , receptor
A dynamic combinatorial library composed of interconverting acylhydrazones has been generated and screened towards inhibition of acetylcholinesterase from the electric ray Torpedo marmorata. Starting from a small set (13) of initial hydrazide and aldehyde building blocks, a library containing possibly 66 different species was obtained in a single operation. Of all possible acylhydrazones formed, active compounds containing two terminal cationic recognition groups separated by an appropriate distance, permitting two‐site binding, could be rapidly identified by using a dynamic deconvolution–screening procedure, based on the sequential removal of starting building blocks. A very potent bis‐pyridinium inhibitor ( K i =1.09 n M , αK i =2.80 n M ) was selected from the process and the contribution of various structural features to inhibitory potency was evaluated.