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Understanding Interactions Between Organophosphates and Nucleic Acids

Abstract

The toxicity of organophosphates (OPs) are well described. They cause neuronal overstimulation which can lead to death. OPs have become tools of suicide and weapons of war due to their ease of access in areas throughout the globe. Thankfully, there are drugs that can inhibit the activity of OPs at their source as well as treating certain symptoms related to exposure. However, current drugs can only treat those whom have already been affected. They do not provide preventative treatment and cannot destroy existing stockpiles. The overabundance of OPs exists because of their ability as herbicides, fungicides and insecticides. Presently, usage of many organophosphates has been banned in many countries but they are still used in certain agricultural areas. This project proposes a novel type of bioscavenger that molecularly sort OPs and their byproducts towards complete enzymatic detoxification. This research precedes the eventual goal of using DNA as a biomolecular scaffold for multienzyme structures by modulating OP binding to increase the efficacy of multistep enzymatic degradation. The studies presented here ascribe short sequences of DNA being able to bind organophosphates as well as the fact that binding is probably sequence dependent. Insight from these experiments will lead to a better understanding of the molecular landscape of substrate-DNA interactions.

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