Catalytic Soman Scavenging by the Y337A/F338A Acetylcholinesterase Mutant Assisted with Novel Site-Directed Aldoximes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F15%3A50003466" target="_blank" >RIV/62690094:18470/15:50003466 - isvavai.cz</a>

Result on the web

<a href="http://pubs.acs.org/doi/abs/10.1021/acs.chemrestox.5b00060" target="_blank" >http://pubs.acs.org/doi/abs/10.1021/acs.chemrestox.5b00060</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.chemrestox.5b00060" target="_blank" >10.1021/acs.chemrestox.5b00060</a>

Result language

angličtina

Original language name

Catalytic Soman Scavenging by the Y337A/F338A Acetylcholinesterase Mutant Assisted with Novel Site-Directed Aldoximes

Original language description

Exposure to the nerve agent soman is difficult to treat due to the rapid dealkylation of the soman-acetylcholinesterase (AChE) conjugate known as aging. Oxime antidotes commonly used to reactivate organophosphate inhibited AChE are ineffective against soman, while the efficacy of the recommended nerve agent bioscavenger butyrylcholinesterase is limited by strictly stoichiometric scavenging. To overcome this limitation, we tested ex vivo, in human blood, and in vivo, in soman exposed mice, the capacity of aging-resistant human AChE mutant Y337A/F338A in combination with oxime HI-6 to act as a catalytic bioscavenger of soman. HI-6 was previously shown in vitro to efficiently reactivate this mutant upon soman, as well as VX, cyclosarin, sarin, and paraoxon, inhibition. We here demonstrate that ex vivo, in whole human blood, 1 muM soman was detoxified within 30 min when supplemented with 0.5 muM Y337A/F338A AChE and 100 muM HI-6. This combination was further tested in vivo. Catalytic scave

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FR - Pharmacology and apothecary chemistry

OECD FORD branch

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Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Chemical research in toxicology

ISSN

0893-228X

e-ISSN

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Volume of the periodical

28

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

1036-1044

UT code for WoS article

000354907500021

EID of the result in the Scopus database

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