Quinn_2018_J.Med.Chem_61_7032

Organophosphorus agents such as sarin and soman that phosphylate the active site serine of the enzyme acetylcholinesterase are notorious and pernicious, not only because they have been used by tyrants to effect mass murder of their own populations but also because they are sought by terrorists to inflict mass casualties on civilian populations. These threats underscore the need to develop effective antidotes against such agents. Phosphylation of acetylcholinesterase produces two adducts, an initial neutral adduct that can be reactivated with oxime nucleophiles, and a subsequent monoanionic adduct (called aged acetylcholinesterase) which has proven over two generations to be impervious to reactivation. This Viewpoint discusses a recent article in the journal that describes the first successful efforts to resurrect the activity of aged acetylcholinesterase.