William K Clay, Anne K Buck, Yiran He, Dalyanne N Hernández Sánchez, Nathan A Ward, Jeremy M Lear, Kenny Q Nguyen, Benjamin H Clark, Ryan J Sapia, Remy F Lalisse, Aishwarya Sriraman, C Linn Cadieux, Craig A McElroy, Christopher S Callam, Christopher M Hadad
Organophosphorus (OP) nerve agents inhibit acetylcholinesterase (AChE), creating a cholinergic crisis in which death can occur. The phosphylated serine residue spontaneously dealkylates to the OP-aged form, which current therapeutics cannot reverse. Soman's aging half-life is 4.2 min, so immediate recovery (resurrection) of OP-aged AChE is needed. In 2018, we showed pyridin-3-ol-based quinone methide precursors (QMPs) can resurrect OP-aged electric eel AChE in vitro , achieving 2% resurrection after 24 h of incubation (pH 7, 4 mM)...
March 31, 2024: Chemical Research in Toxicology