Macek Hrvat_2016_Chem.Biol.Interact_259_148

Reference

Title : HI-6 assisted catalytic scavenging of VX by acetylcholinesterase choline binding site mutants - Macek Hrvat_2016_Chem.Biol.Interact_259_148
Author(s) : Macek Hrvat N , Zunec S , Taylor P , Radic Z , Kovarik Z
Ref : Chemico-Biological Interactions , 259 :148 , 2016
Abstract :

The high toxicity of organophosphorus compounds originates from covalent inhibition of acetylcholinesterase (AChE), an essential enzyme in cholinergic neurotransmission. Poisonings that lead to life-threatening 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.

PubMedSearch : Macek Hrvat_2016_Chem.Biol.Interact_259_148
PubMedID: 27083141
Gene_locus related to this paper: human-ACHE

Related information

Mutation Y337A\/F338A_human-ACHE    Y337A_human-ACHE
Inhibitor Y337A\/F338A_human-ACHE    Y337A_human-ACHE    VX
Gene_locus Y337A\/F338A_human-ACHE    Y337A_human-ACHE    VX    human-ACHE
Reactivator Y337A\/F338A_human-ACHE    Y337A_human-ACHE    VX    human-ACHE    HI-6

Citations formats

Macek Hrvat N, Zunec S, Taylor P, Radic Z, Kovarik Z (2016)
HI-6 assisted catalytic scavenging of VX by acetylcholinesterase choline binding site mutants
Chemico-Biological Interactions 259 :148

Macek Hrvat N, Zunec S, Taylor P, Radic Z, Kovarik Z (2016)
Chemico-Biological Interactions 259 :148