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
Life
CBRN - CBRN Protection
EELS - Earth, Environmental and Life Sciences
Pharmacology
Acetylcholinesterase
Nerve agent
Oxime
Peripheral site
Reactivation
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