ABSTRACT
This chapter discusses the state of stoichiometric and catalytic bioscavenger development. Bioscavenger proteins have the potential to prevent or treat nerve agent poisoning. Bioscavengers detoxify in two ways: stoichiometric bioscavengers sequester nerve agents, removing them from circulation, while catalytic bioscavengers enzymatically degrade nerve agents. Organophosphorus nerve agent (OPNA) poisoning leads to an array of symptoms associated with neurotransmitter dysregulation. Organophosphate acid anhydrolase is a 517-amino acid bimetalohydrolase containing a small N-terminal domain and a large C-terminal domain, structured as a “pitta bread” fold. A high concentration of stoichiometric bioscavenger is required to protect against multiple LD50s of a nerve agent exposure. The antidotal and therapeutic potentials of a human B-family esterase, endowed with a high turnover rate for OPNA binding and hydrolysis, are great. Butyrylcholinesterase has demonstrated protection against multiple G- and V-series nerve agents across a range of animal models.
