Print Email Facebook Twitter Peripheral site ligand-oxime conjugates: A novel concept towards reactivation of nerve agent-inhibited human acetylcholinesterase Title Peripheral site ligand-oxime conjugates: A novel concept towards reactivation of nerve agent-inhibited human acetylcholinesterase Author de Koning, M.C. Joosen, M.J.A. Noort, D. van Zuylen, A. Tromp, M.C. Publication year 2011 Abstract 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. © 2010 Elsevier Ltd. All rights reserved. Subject LifeCBRN - CBRN ProtectionEELS - Earth, Environmental and Life SciencesPharmacologyAcetylcholinesteraseNerve agentOximePeripheral siteReactivation To reference this document use: http://resolver.tudelft.nl/uuid:48a19a98-7074-4346-a800-348973b39a77 DOI https://doi.org/10.1016/j.bmc.2010.10.059 TNO identifier 426353 ISSN 0968-0896 Source Bioorganic and Medicinal Chemistry, 19 (1), 588-594 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.