scholarly journals Chemical Synthesis of Two Series of Nerve Agent Model Compounds and Their Stereoselective Interaction with Human Acetylcholinesterase and Human Butyrylcholinesterase

2009 ◽  
Vol 22 (10) ◽  
pp. 1669-1679 ◽  
Author(s):  
Nora H. Barakat ◽  
Xueying Zheng ◽  
Cynthia B. Gilley ◽  
Mary MacDonald ◽  
Karl Okolotowicz ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Nerve Agent ◽  
Model Compounds ◽  
Agent Model ◽  
Human Butyrylcholinesterase

scholarly journals Direct detection of the hydrolysis of nerve agent model compounds using a fluorescent probe

2010 ◽  
Vol 187 (1-3) ◽  
pp. 330-334 ◽  
Author(s):  
Xueying Zheng ◽  
Karl Okolotowicz ◽  
Beilin Wang ◽  
Mary MacDonald ◽  
John R. Cashman ◽  
...  
Keyword(s):  
Fluorescent Probe ◽  
Direct Detection ◽  
Nerve Agent ◽  
Model Compounds ◽  
Agent Model ◽  
Hydrolysis Of

scholarly journals Enhanced Stability of Blood Matrices Using a Dried Sample Spot Assay To Measure Human Butyrylcholinesterase Activity and Nerve Agent Adducts

2015 ◽  
Vol 87 (11) ◽  
pp. 5723-5729 ◽  
Author(s):  
Jonas W. Perez ◽  
Brooke G. Pantazides ◽  
Caroline M. Watson ◽  
Jerry D. Thomas ◽  
Thomas A. Blake ◽  
...  
Keyword(s):  
Nerve Agent ◽  
Sample Spot ◽  
Butyrylcholinesterase Activity ◽  
Enhanced Stability ◽  
Human Butyrylcholinesterase

A study of nerve agent model organophosphonate binding with manganese-A2B-corrole and -A2B2-porphyrin systems

Polyhedron ◽  
2009 ◽  
Vol 28 (12) ◽  
pp. 2418-2430 ◽  
Author(s):  
Kibong Kim ◽  
Inkoo Kim ◽  
Nilkamal Maiti ◽  
Seong Jung Kwon ◽  
Daniela Bucella ◽  
...  
Keyword(s):  
Nerve Agent ◽  
Agent Model

scholarly journals Corrigendum to: “A Novel, Modified Human Butyrylcholinesterase Catalytically Degrades the Chemical Warfare Nerve Agent, Sarin”

2020 ◽  
Vol 177 (1) ◽  
pp. 300-300
Author(s):  
Kevin G McGarry ◽  
Remy F Lalisse ◽  
Robert A Moyer ◽  
Kristyn M Johnson ◽  
Alexi M Tallan ◽  
...  
Keyword(s):  
Nerve Agent ◽  
Chemical Warfare ◽  
Human Butyrylcholinesterase

Human butyrylcholinesterase efficacy against nerve agent exposure

2017 ◽  
Vol 31 (5) ◽  
pp. e21886 ◽  
Author(s):  
Beth A. Reed ◽  
Carol L. Sabourin ◽  
David E. Lenz
Keyword(s):  
Nerve Agent ◽  
Human Butyrylcholinesterase

Studies of dialkyl ether phospholipids. I. Chemical synthesis of some model compounds

1970 ◽  
Vol 48 (5) ◽  
pp. 585-593 ◽  
Author(s):  
Jung-Shou Chen ◽  
Peter G. Barton
Keyword(s):  
Chemical Synthesis ◽  
Free Product ◽  
Methyl Iodide ◽  
Cadmium Chloride ◽  
Chloride Complex ◽  
Protecting Group ◽  
Subsequent Reaction ◽  
Model Compounds ◽  
Ether Phospholipids ◽  
Catalytic Hydrogenolysis

The syntheses of three 1,2-dialkyl-sn-glycero-3-phosphates and one new 1,2-dialkyl-sn-glycerol are described. 1,2-Dioctadecyl-sn-glycero-3-phosphate was obtained by phosphorylation of 1,2-dioctadecyl-sn-glycerol with diphenylphosphorodichloridate and subsequent catalytic hydrogenolysis. 1,2-Dioctadecyl-sn-glycero-3-(methyl)phosphorylcholine was prepared by phosphorylation of the same dialkyl glycerol with methylphosphorodichloridate and subsequent reaction with choline iodide. 1,2-Dimethyl-sn-glycerol was prepared by treatment of 3-benzyl-sn-glycerol with methyl iodide and KOH followed by hydrogenolysis to remove the protecting group. This compound was then phosphorylated with phenylphosphorodichloridate, the product allowed to react with choline iodide, and the iodide-free product hydrogenated catalytically to yield 1,2-dimethyl-sn-glycero-3-phosphorylcholine which was characterized as the cadmium chloride complex. Some improvements in an established synthesis of 1,2-dioctadecyl-sn-glycerol are described.

scholarly journals Catalytic detoxification of nerve agent and pesticide organophosphates by butyrylcholinesterase assisted with non-pyridinium oximes

2013 ◽  
Vol 450 (1) ◽  
pp. 231-242 ◽  
Author(s):  
Zoran Radić ◽  
Trevor Dale ◽  
Zrinka Kovarik ◽  
Suzana Berend ◽  
Edzna Garcia ◽  
...  
Keyword(s):  
Kinetic Analysis ◽  
Hydroxy Group ◽  
Ex Vivo ◽  
Nerve Agent ◽  
Oxime Group ◽  
Quaternary Nitrogen ◽  
Pyridinium Oximes ◽  
Human Butyrylcholinesterase

In the present paper we show a comprehensive in vitro, ex vivo and in vivo study on hydrolytic detoxification of nerve agent and pesticide OPs (organophosphates) catalysed by purified hBChE (human butyrylcholinesterase) in combination with novel non-pyridinium oxime reactivators. We identified TAB2OH (2-trimethylammonio-6-hydroxybenzaldehyde oxime) as an efficient reactivator of OP–hBChE conjugates formed by the nerve agents VX and cyclosarin, and the pesticide paraoxon. It was also functional in reactivation of sarin- and tabun-inhibited hBChE. A 3–5-fold enhancement of in vitro reactivation of VX-, cyclosarin- and paraoxon-inhibited hBChE was observed when compared with the commonly used N-methylpyridinium aldoxime reactivator, 2PAM (2-pyridinealdoxime methiodide). Kinetic analysis showed that the enhancement resulted from improved molecular recognition of corresponding OP–hBChE conjugates by TAB2OH. The unique features of TAB2OH stem from an exocyclic quaternary nitrogen and a hydroxy group, both ortho to an oxime group on a benzene ring. pH-dependences reveal participation of the hydroxy group (pKa=7.6) forming an additional ionizing nucleophile to potentiate the oxime (pKa=10) at physiological pH. The TAB2OH protective indices in therapy of sarin- and paraoxon-exposed mice were enhanced by 30–60% when they were treated with a combination of TAB2OH and sub-stoichiometric hBChE. The results of the present study establish that oxime-assisted catalysis is feasible for OP bioscavenging.

scholarly journals Non-quaternary oximes detoxify nerve agents and reactivate nerve agent-inhibited human butyrylcholinesterase

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Gabriel Amitai ◽  
Alexander Plotnikov ◽  
Shira Chapman ◽  
Shlomi Lazar ◽  
Rellie Gez ◽  
...  
Keyword(s):  
Small Molecules ◽  
High Throughput Screening ◽  
Reaction Rates ◽  
Nerve Agents ◽  
Nerve Agent ◽  
The Novel ◽  
Quaternary Compounds ◽  
Toxicological Studies ◽  
Pyridinium Oximes ◽  
Human Butyrylcholinesterase

AbstractGovernment-sanctioned use of nerve agents (NA) has escalated dramatically in recent years. Oxime reactivators of organophosphate (OP)-inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) serve as antidotes toward poisoning by OPNAs. The oximes used as therapeutics are quaternary compounds that cannot penetrate the blood–brain barrier (BBB). There remains an urgent need for the development of next generation OPNA therapeutics. We have developed two high-throughput screening (HTS) assays using a fluorogenic NA surrogate, O-ethyl methylphosphonyl O-4-methyl-3-cyano-coumarin (EMP-MeCyC). EMP-MeCyC detoxification and EMP-BChE reactivation screening campaigns of ~155,000 small molecules resulted in the identification of 33 nucleophile candidates, including non-quaternary oximes. Four of the oximes were reactivators of both Sarin- and VX-inhibited BChE and directly detoxified Sarin. One oxime also detoxified VX. The novel reactivators included a non-quaternary pyridine amidoxime, benzamidoxime, benzaldoxime and a piperidyl-ketoxime. The VX-inhibited BChE reactivation reaction rates by these novel molecules were similar to those observed with known bis-quaternary reactivators and faster than mono-quaternary pyridinium oximes. Notably, we discovered the first ketoxime reactivator of OP-ChEs and detoxifier of OPNAs. Preliminary toxicological studies demonstrated that the newly discovered non-quaternary oximes were relatively non-toxic in mice. The discovery of unique non-quaternary oximes opens the door to the design of novel therapeutics and decontamination agents following OPNA exposure.

scholarly journals Neuroprotective effects of a catalytic antioxidant in a rat nerve agent model

Redox Biology ◽  
2019 ◽  
Vol 20 ◽  
pp. 275-284 ◽  
Author(s):  
Li-Ping Liang ◽  
Jennifer N. Pearson-Smith ◽  
Jie Huang ◽  
Brian J. Day ◽  
Manisha Patel
Keyword(s):  
Nerve Agent ◽  
Neuroprotective Effects ◽  
Agent Model ◽  
Rat Nerve ◽  
Catalytic Antioxidant
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