In situ selection of lead compounds by click chemistry: target-guided optimization of acetylcholinesterase inhibitors

…, Z Radic, R Manetsch, J Raushel, P Taylor…

Index: Krasinski, Antoni; Radic, Zoran; Manetsch, Roman; Raushel, Jessica; Taylor, Palmer; Sharpless, K. Barry; Kolb, Hartmuth C. Journal of the American Chemical Society, 2005 , vol. 127, # 18 p. 6686 - 6692

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Citation Number: 308

Abstract

The target-guided, in situ click chemistry approach to lead discovery has been successfully employed for discovering acetylcholinesterase (AChE) inhibitors by incubating a selected enzyme/tacrine azide combination with a variety of acetylene reagents that were not previously known to interact with the enzyme's peripheral binding site. The triazole products, formed by the enzyme, were identified by HPLC-mass spectrometry analysis of the crude ...