Organophosphate detoxification treatment by peptides

Organophosphate compounds (OPCs) nerve agents pose a threat to human beings in war zones. In day to day life, OPCs can be found in pesticides products at low concentrations. OPCs inhibit the enzyme acetylcholine esterase (AChE) which hydrolyzes the neurotransmitter, acetylcholine into choline and acetate.

Esterases enzymes are used as bioscavangers to remove OPCs from the blood, in case of exposure. Yet, the large amount of enzymes required for a stoichiometric treatment, the limited supply of these proteins, their low hydrolytic activity towards various OP compounds, have prevented enzymes from being an effective antidote for medical uses. Despite the difficulties, bioscavangers are the most promising treatment for OPs infected patients.

In our studies we demonstrate the potential use of synthetic peptides as bioscavengers. Previously, we screened designed- single strand and double strand β-sheet peptides for OPCs adsorbing. The peptides presented the AChE catalytic triad residues (His, Glu and Ser) at different orders and exhibited different charge. The interactions between paraoxon (OPCs model molecule) and the peptides were evaluated at different concentrations in the micromolar range, qualitatively by CD, ThT assays and TEM imaging as well as quantitatively by adsorption measurements. The peptide ssESH, with the sequence Ac-Cys-Phe-Glu-Phe-Ser-Phe-His-Phe-Pro-NH₂, was found to stand out by its ability to bind paraoxon. In preliminary in-vivo studies ssESH was found to be nontoxic as well as effective in lowering OPCs toxic signs in a manner comparable to the standard treatment by atropine and oxime. These results point to the potential application of ssESH peptide as a bioscavenger in OPCs intoxication.