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Oxime assisted catalytic scavenging of nerve agents by acetylcholinesterase choline binding site mutants (CROSBI ID 637673)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija

Maček Hrvat, Nikolina ; Žunec, Suzana ; Katalinić, Maja ; Taylor, Palmer ; Radić, Zoran ; Kovarik, Zrinka Oxime assisted catalytic scavenging of nerve agents by acetylcholinesterase choline binding site mutants // Book of Abstracts of Bioscience Review 2016 Conference, Gunpowder, Maryland, SAD. 2016

Podaci o odgovornosti

Maček Hrvat, Nikolina ; Žunec, Suzana ; Katalinić, Maja ; Taylor, Palmer ; Radić, Zoran ; Kovarik, Zrinka

engleski

Oxime assisted catalytic scavenging of nerve agents by acetylcholinesterase choline binding site mutants

Newly considered strategies in medical protection against nerve agents focus on the use of exogenously administered butyrylcholinesterase (BChE). The overall idea is to administer such an enzyme in combination with a specific oxime, to scavenge an organophosphate (OP) before it can reach and inhibit native acetylcholinesterase (AChE), thus helping organism detoxification from the excess OP. However, oxime antidotes commonly used to reactivate OP inhibited AChE are ineffective against soman and tabun, while the efficacy of the recommended nerve agent bioscavenger BChE is limited by strictly stoichiometric scavenging. Our previous research showed that AChE mutagenesis can enable aldoximes to substantially accelerate the reactivation of OP-enzyme conjugates, while dramatically slowing down rates of OP-conjugate dealkylation (aging). Herein we demonstrated through a combination of in silico, in vitro, ex vivo, and in vivo results, a feasible approach to the development of an oxime assisted catalytic bioscavenger of soman, tabun and VX based on human AChE mutants modified at the choline binding site (Y337A and an aging resistant Y337A/F338A) in combination with its efficient reactivator. Ultimatelly, the oxime assisted catalytic scavenging of the nerve agents in mice improved therapeutic outcomes preventing lethality and resulted in a delayed onset of toxicity symptoms.

aging ; AChE mutants ; Y337A ; Y337A/F338A

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Podaci o prilogu

2016.

nije evidentirano

objavljeno

Podaci o matičnoj publikaciji

Book of Abstracts of Bioscience Review 2016 Conference, Gunpowder, Maryland, SAD

Podaci o skupu

The Bioscience Review 2016 Conference

poster

06.06.2016-09.06.2016

Gunpowder (MD), Sjedinjene Američke Države

Povezanost rada

Kemija