Pharmacology, Toxicology and Environmental Health Commons^™

Quantitative Structure-Activity Relationships For Organophosphates Binding To Trypsin And Chymotrypsin, Christopher Daniel Ruark

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Organophosphate (OP) nerve agents such as sarin, soman, tabun, and O-ethyl S-[2-(diisopropylamino) ethyl] methylphosphonothioate (VX) do not react solely with acetylcholinesterase (AChE). Evidence suggests that a wide range of cholinergic-independent pathways are also targeted, including serine proteases. These proteases comprise nearly one-third of all known proteases and play major roles in synaptic plasticity, learning, memory, neuroprotection, wound healing, cell signaling, inflammation, blood coagulation and protein processing. Inhibition of these proteases by OPs was found to exert a wide range of noncholinergic effects depending on the type of OP, the dose, and the duration of exposure. Consequently, in order to understand …