ChemInform Abstract: Design, Synthesis and Evaluation of New α-Nucleophiles for the Hydrolysis of Organophosphorus Nerve Agents: Application to the Reactivation of Phosphorylated Acetylcholinesterase.

ChemInform ◽  
2011 ◽  
Vol 42 (52) ◽  
pp. no-no
Author(s):  
Geraldine Saint-Andre ◽  
Maria Kliachyna ◽  
Sanjeevarao Kodepelly ◽  
Ludivine Louise-Leriche ◽  
Emilie Gillon ◽  
...  
Tetrahedron ◽  
2011 ◽  
Vol 67 (34) ◽  
pp. 6352-6361 ◽  
Author(s):  
Géraldine Saint-André ◽  
Maria Kliachyna ◽  
Sanjeevarao Kodepelly ◽  
Ludivine Louise-Leriche ◽  
Emilie Gillon ◽  
...  

2020 ◽  
Vol 12 (13) ◽  
pp. 14702-14720 ◽  
Author(s):  
Kent O. Kirlikovali ◽  
Zhijie Chen ◽  
Timur Islamoglu ◽  
Joseph T. Hupp ◽  
Omar K. Farha

1999 ◽  
Vol 40 (2) ◽  
pp. 281-284 ◽  
Author(s):  
Pierre-Yves Renard ◽  
Philippe Vayron ◽  
Frédéric Taran ◽  
Charles Mioskowski

2020 ◽  
Vol 21 (9) ◽  
pp. 3867-3877
Author(s):  
Libin Zhang ◽  
Hironobu Murata ◽  
Gabriel Amitai ◽  
Paige N. Smith ◽  
Krzysztof Matyjaszewski ◽  
...  

Author(s):  
Anja Köhler ◽  
Benjamin Escher ◽  
Laura Job ◽  
Marianne Koller ◽  
Horst Thiermann ◽  
...  

AbstractHighly toxic organophosphorus nerve agents, especially the extremely stable and persistent V-type agents such as VX, still pose a threat to the human population and require effective medical countermeasures. Engineered mutants of the Brevundimonas diminuta phosphotriesterase (BdPTE) exhibit enhanced catalytic activities and have demonstrated detoxification in animal models, however, substrate specificity and fast plasma clearance limit their medical applicability. To allow better assessment of their substrate profiles, we have thoroughly investigated the catalytic efficacies of five BdPTE mutants with 17 different nerve agents using an AChE inhibition assay. In addition, we studied one BdPTE version that was fused with structurally disordered PAS polypeptides to enable delayed plasma clearance and one bispecific BdPTE with broadened substrate spectrum composed of two functionally distinct subunits connected by a PAS linker. Measured kcat/KM values were as high as 6.5 and 1.5 × 108 M−1 min−1 with G- and V-agents, respectively. Furthermore, the stereoselective degradation of VX enantiomers by the PASylated BdPTE-4 and the bispecific BdPTE-7 were investigated by chiral LC–MS/MS, resulting in a several fold faster hydrolysis of the more toxic P(−) VX stereoisomer compared to P(+) VX. In conclusion, the newly developed enzymes BdPTE-4 and BdPTE-7 have shown high catalytic efficacy towards structurally different nerve agents and stereoselectivity towards the toxic P(−) VX enantiomer in vitro and offer promise for use as bioscavengers in vivo.


1996 ◽  
Vol 61 (24) ◽  
pp. 8407-8413 ◽  
Author(s):  
Yu-Chu Yang ◽  
Linda L. Szafraniec ◽  
William T. Beaudry ◽  
Dennis K. Rohrbaugh ◽  
Lawrence R. Procell ◽  
...  
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