A HTS Assay for the Detection of Organophosphorus Nerve Agent Scavengers |
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Authors: | Ludivine Louise‐Leriche Emilia Pǎunescu Géraldine Saint‐André Rachid Baati Anthony Romieu Alain Wagner Pierre‐Yves Renard |
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Affiliation: | 1. Equipe de Chimie Bio‐Organique, COBRA—CNRS UMR 6014 & FR 3038 rue Tesnière, 76130 Mont‐Saint‐Aignan (France), Fax: (+33)?235‐52‐29‐59;2. Université de Rouen, IRCOF rue Tesnière, 76130 Mont Saint Aignan (France);3. Laboratoire de Chimie des Systèmes Fonctionnels CNRS/UMR7199, Faculté de Pharmacie, Université de Strasbourg, BP 24, 67401 Illkirch (France), Fax: (+33)?3368‐854‐301;4. Institut Universitaire de France, 103 boulevard Saint Michel, 75005 Paris (France) |
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Abstract: | A new pro‐fluorescent probe aimed at a HTS assay of scavengers is able to selectively and efficiently cleave the P? S 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 P? Oaryl bond cleavage, whereas our approach uses a self‐immolative linker strategy that allows the detection of phosphonothioase activity with respect to a non‐activated P? Salkyl 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. |
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Keywords: | fluorescent probes hydrolysis nerve agent scavengers organophosphonothioase activity phosphorus |
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