Enantioseparation, in vitro testing, and structural characterization of triple-binding reactivators of organophosphate-inhibited cholinesterases
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F20%3A00531737" target="_blank" >RIV/61388963:_____/20:00531737 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1042/BCJ20200192" target="_blank" >https://doi.org/10.1042/BCJ20200192</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1042/BCJ20200192" target="_blank" >10.1042/BCJ20200192</a>
Alternative languages
Result language
angličtina
Original language name
Enantioseparation, in vitro testing, and structural characterization of triple-binding reactivators of organophosphate-inhibited cholinesterases
Original language description
The enantiomers of racemic 2-hydroxyimino-N-(azidophenylpropyl)acetamide-derived triple-binding oxime reactivators were separated, and tested for inhibition and reactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibited with tabun (GA), cyclosarin (GF), sarin (GB), and VX. Both enzymes showed the greatest affinity toward the methylimidazole derivative (III) of 2-hydroxyimino-N-(azidophenylpropyl)acetamide (I). The crystal structure was determined for the complex of oxime III within human BChE, confirming that all three binding groups interacted with active site residues. In the case of BChE inhibited by GF, oximes I (kr = 207 M−1 min−1) and III (kr = 213 M−1 min−1) showed better reactivation efficiency than the reference oxime 2-PAM. Finally, the key mechanistic steps in the reactivation of GF-inhibited BChE with oxime III were modeled using the PM7R6 method, stressing the importance of proton transfer from Nε of His438 to Oγ of Ser203 for achieving successful reactivation.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biochemical Journal
ISSN
0264-6021
e-ISSN
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Volume of the periodical
477
Issue of the periodical within the volume
15
Country of publishing house
GB - UNITED KINGDOM
Number of pages
20
Pages from-to
2771-2790
UT code for WoS article
000575187600002
EID of the result in the Scopus database
2-s2.0-85089301518