Nonenzymatic, self-elimination degradation mechanism of glutathione

In the present in vitro studies, evidence is provided showing that glutathione (GSH) can undergo spontaneous, nonenzymatic auto-degradation. The initial cleavage of the Glu-Cys bond involves nucleophilic attack of the N-terminal amino group of GSH at the g-carbonyl side chain, followed by an unusual cleavage of the Cys-Gly amide bond that is complete within 3-5 weeks in the physiological pH range. These observations may be useful for the development of novel biodegradable polymers and releasable prodrugs for sustained and targeted drug delivery applications.