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A HTS Assay for the Detection of Organophosphorus Nerve Agent Scavengers
Author(s) -
LouiseLeriche Ludivine,
Pǎunescu Emilia,
SaintAndré Géraldine,
Baati Rachid,
Romieu Anthony,
Wagner Alain,
Renard PierreYves
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200902986
Subject(s) - nerve agent , chemistry , cleave , high throughput screening , combinatorial chemistry , linker , fluorescence , nucleophile , hydroxamic acid , substrate (aquarium) , bond cleavage , cleavage (geology) , biochemistry , enzyme , stereochemistry , catalysis , physics , oceanography , geotechnical engineering , quantum mechanics , fracture (geology) , computer science , engineering , acetylcholinesterase , geology , operating system
A new pro‐fluorescent probe aimed at a HTS assay of scavengers is able to selectively and efficiently cleave the PS bond of organophosphorus nerve agents and by this provides non‐toxic phosphonic acid has been designed and synthesised. The previously described pro‐fluorescent probes were based on a conventional activated POaryl bond cleavage, whereas our approach uses a self‐immolative linker strategy that allows the detection of phosphonothioase activity with respect to a non‐activated PSalkyl bond. Further, we have also developed and optimised a high‐throughput screening assay for the selection of decontaminants (chemical or biochemical scavengers) that could efficiently hydrolyse highly toxic V ‐type nerve agents. A preliminary screening, realised on a small α‐nucleophile library, allowed us to identify some preliminary “hits”, among which pyridinealdoximes, α‐oxo oximes, hydroxamic acids and, less active but more original, amidoximes were the most promising. Their selective phosphonothioase activity has been further confirmed by using PhX as the substrate, and thus they offer new perspectives for the synthesis of more potent V nerve agent scavengers.