The basis of my research was to study whether “GSMOI”, the Glutathione (GSH) conjugate with 3-Methyleneoxindole (MOI) is a mechanism-based inhibitor of the anti-cancer target enzyme Glyoxalase 1 (GxI). To fully understand the chemical mechanism, my research question asks whether the elimination of GSH from GSMOI follows the E1, E2, or E1cb chemical mechanism. To determine which mechanism this elimination follows, GSMOI was synthesized by two different methods producing (1) a solid sample, and (2) a working aqueous stock solution in phosphate buffer. The synthesized products were characterized using NMR and UV-Vis spectroscopy. Using the UV-Vis spectrophotometer chemical kinetics assays were conducted at pH 7 to determine the rate at which GSMOI breaks down into MOI. Furthermore, C-3 proton exchange kinetics on GSMOI were determined by observing the rate of hydrogen to deuterium exchange by NMR. Taken together, these data strongly suggest an E1cb mechanism for GSMOI elimination. This research is significant because if GSMOI is a potential cancer therapeutic, understanding how it reacts under physiological conditions is key to using it for pharmaceutical purposes.  This research was funded by a summer 2014 grant from the Bridgewater State University Office of Undergraduate Research.

Investigation of the aqueous chemistry in the elimination of glutathione from the glutathione-3-methyleneoxindole conjugate: A potential therapeutic agent

249th National Meeting (2015)

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