Progress towards BChE tethered with a reactivating ligand: a pseudo-catalytic nerve agent bioscavenger (Poster)

Human butyrylcholinesterase (hBChE) constitutes a promising alternative to presently available protection against organophosphate (OP) poisoning. This biological scavenger avoids the reaction of the OP with human acetylcholinesterase (hAChE) by covalent sequestration. One major drawback of the stoichiometric nature of action is the high dose and associated costs that are needed in order to provide adequate protection. Co-administration of the currently approved oximes, such as HI-6 and pralidoxime, to reactivate the OP-inhibited BChE and to establish a pseudo-catalytic function failed as it was demonstrated that the reactivation of OP-inhibited BChE by these oximes is too slow. We are currently exploring an alternative approach that comprises the chemical engineering of hBChE with its own reactivating chemical functionality that will effectively hydrolyze the chemical bond between the active site serine and the organophosphate moiety by a proximity-driven reaction.