Nerve Agent Analogues That Produce Authentic Soman, Sarin, Tabun, and Cyclohexyl Methylphosphonate-Modified Human Butyrylcholinesterase
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چکیده
منابع مشابه
Stereoselective detoxification of chiral sarin and soman analogues by phosphotriesterase.
The catalytic activity of the bacterial phosphotriesterase (PTE) toward a series of chiral analogues of the chemical warfare agents sarin and soman was measured. Chemical procedures were developed for the chiral syntheses of the S(P)- and R(P)-enantiomers of O-isopropyl p-nitrophenyl methylphosphonate (sarin analogue) in high enantiomeric excess. The R(P)-enantiomer of the sarin analogue (k(cat...
متن کاملStructure-activity analysis of aging and reactivation of human butyrylcholinesterase inhibited by analogues of tabun.
hBChE [human BChE (butyrylcholinesterase)] naturally scavenges OPs (organophosphates). This bioscavenger is currently in Clinical Phase I for pretreatment of OP intoxication. Phosphylated ChEs (cholinesterases) can undergo a spontaneous time-dependent process called 'aging' during which the conjugate is dealkylated, leading to creation of an enzyme that cannot be reactivated. hBChE inhibited by...
متن کاملPhosphotriesterase variants with high methylphosphonatase activity and strong negative trade-off against phosphotriesters.
The most lethal organophosphorus nerve agents (NA), like sarin, soman, agent-VX and Russian-VX, share a methylphosphonate moiety. Pseudomonas diminuta phosphotriesterase (PTE) catalyses the hydrolysis of methylphosphonate NA analogues with a catalytic efficiency orders of magnitude lower than that towards the pesticide paraoxon. With a view to obtaining PTE variants that more readily accept met...
متن کاملHuman 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...
متن کاملPyridinium, imidazolium and quinuclidinium compounds: toxicity and antidotal effects against the nerve agents Tabun and Soman.
This paper discusses the toxicity and antidotal effects of 32 compounds. Screening studies have shown that these compounds combined with atropine are effective antidotes against the organophosphate nerve agents Tabun and/or Soman, having a therapeutic factor equal or greater than 2.0 when tested in mice or rats. We analysed the results of these studies, and recommend that these compounds should...
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ژورنال
عنوان ژورنال: Chemical Research in Toxicology
سال: 2009
ISSN: 0893-228X,1520-5010
DOI: 10.1021/tx900090m