Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin

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Human carboxylesterase 1 stereoselectively binds the nerve agent cyclosarin and spontaneously hydrolyzes the nerve agent sarin.

Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with the goal of preventing nerve agent toxicity and protecting against the long-term side effects of these agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based...

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Theoretical investigation about the adsorption of the Sarin nerve agent on C20 fullerene and its boron-doped derivative

Sarin is a very toxic organophosphorus chemical warfare agent which has been used in different wars. According to an immediate demand of detection, secure approachs to break down this toxic nerve agent, the study on decomposition of sarin achieve significance. In this work, we have made endeavors of discovering an approach to neutralize this hazardous kind by adsorption of this molecule by C20 ...

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Structural and Biochemical Analysis Reveals the Stereoselectivity of Inhibition and Reactivation of Human Carboxylesterase 1 for the Nerve Agents Sarin, Soman, and Cyclosarin

Departments of Chemistry (M.R.R.) and Biochemistry and Biophysics (A.C.H., C.D.F., M.R.R), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; U.S. Army Medical Research Institute of Chemical Defense (T.C.O., D.M.C.), Aberdeen Proving Ground, Maryland; Human BioMolecular Research Institute (M.M., J.R.C.), San Diego, California; Department of Molecular Pharmacology (M.W., C...

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Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme

Organophosphorus (OP) nerve agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart nerve agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the targe...

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A lab-on-a-chip for detection of nerve agent sarin in blood.

Sarin (C(4)H(10)FO(2)P,O-isopropyl methylphosphonofluoridate) is a colourless, odourless and highly toxic phosphonate that acts as a cholinesterase inhibitor and disrupts neuromuscular transmission. Sarin and related phosphonates are chemical warfare agents, and there is a possibility of their application in a military or terrorist attack. This paper reports a lab-on-a-chip device for detecting...

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ژورنال

عنوان ژورنال: Molecular Pharmacology

سال: 2010

ISSN: 0026-895X,1521-0111

DOI: 10.1124/mol.109.062356