Bioorganic & Medicinal Chemistry 2011-01-01

Peripheral site ligand-oxime conjugates: A novel concept towards reactivation of nerve agent-inhibited human acetylcholinesterase.

M C de Koning, M J A Joosen, D Noort, A van Zuylen, M C Tromp

文献索引：Bioorg. Med. Chem. 19(1) , 588-94, (2011)

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摘要

A conceptually novel approach to the design of reactivators of nerve agent-inhibited acetylcholinesterase (AChE) is presented. The concept comprises the linkage of a peripheral site ligand via a spacer to a reactivating moiety with the eventual goal to develop non-ionic reactivators with sufficient affinity for AChE to induce reactivation and potentially improved blood-brain barrier penetration. Herein, the first step towards that goal-the synthesis and biological evaluation of a peripheral site ligand conjugated to a charged pyridinium oxime is discussed. It was found, that the introduction of the peripheral site ligand not only increased affinity of the construct for AChE but also enhanced reactivation of nerve agent-inhibited AChE.Copyright © 2010 Elsevier Ltd. All rights reserved.