Naslov
HI-6 assisted catalytic scavenging of VX by acetylcholinesterase choline binding site mutants

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

Izvornik
Chemico-biological interactions (0009-2797) 259 (2016), Part B; 148-153

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Antidotes ; Cholinesterase ; Nerve agents ; Organophosphates ; Oximes ; Reactivation ; 2-PAM

Sažetak
The high toxicity of organophosphorus compounds originates from covalent inhibition of acetylcholinesterase (AChE), an essential enzyme in cholinergic neurotransmission. Poisonings that lead to lifethreatening toxic manifestations require immediate treatment that combines administration of anticholinergic drugs and an aldoxime as a reactivator of AChE. An alternative approach to reduce the in vivo toxicity of OPs focuses on the use of bioscavengers against the parent organophosphate. 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 demonstrate an efficient HI-6-assisted VX detoxification, both ex vivo in human blood and in vivo in mice by hAChE mutants modified at the choline binding site (Y337A and Y337A/F338A). The catalytic scavenging of VX in mice improved therapeutic outcomes preventing lethality and resulted in a delayed onset of toxicity symptoms.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA