ArticleChemico-biological interactions2016
HI-6 assisted catalytic scavenging of VX by acetylcholinesterase choline binding site mutants.
Article in Chemico-biological interactions, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 22 citations in OpenAlex.
- Engineered acetylcholinesterase-loaded dissolvable microneedles mitigate dermal toxicity by targeting trichlorfon binding and metabolic pathway modulation.Materials today. Bio · 2026Article
- Click-chemistry-derived oxime library reveals efficient reactivators of nerve agent-inhibited butyrylcholinesterase suitable for pseudo-catalytic bioscavenging.Archives of toxicology · 2025Article
- Counteracting poisoning with chemical warfare nerve agents.Arhiv za higijenu rada i toksikologiju · 2020Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
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.
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Registered trials
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