Analogues with fluorescent leaving groups for screening and selection of enzymes that efficiently hydrolyze organophosphorus nerve agents

L Briseno-Roa, J Hill, S Notman, D Sellers…

Index: Briseno-Roa, Luis; Hill, Jim; Notman, Stuart; Sellers, David; Smith, Andy P.; Timperley, Christopher M.; Wetherell, Janet; Williams, Nichola H.; Williams, Gareth R.; Fersht, Alan R.; Griffiths, Andrew D. Journal of Medicinal Chemistry, 2006 , vol. 49, # 1 p. 246 - 255

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Citation Number: 68

Abstract

Enzymes that efficiently hydrolyze highly toxic organophosphorus nerve agents could potentially be used as medical countermeasures. As sufficiently active enzymes are currently unknown, we synthesized twelve fluorogenic analogues of organophosphorus nerve agents with the 3-chloro-7-oxy-4-methylcoumarin leaving group as probes for high- throughput enzyme screening. This set included analogues of the pesticides paraoxon, ...