Characterisation of the decomposition behaviour of S-nitrosoglutathione and a new class of analogues: S-Nitrosophytochelatins

S-Nitrosoglutathione (GSNO) is one of the most abundant S-nitrosothiols present in the body, playing an important role in many important physiological functions. Depletion of GSNO in some pathophysiological conditions makes GSNO a potentially interesting therapeutic molecule. Phytochelatins are glutathione analogues with the following structure: (gamma-glutamyl-cysteine)(n)-glycine. S-Nitroso derivatives of phytochelatins (SNOPCs) carry a greater number of S-nitrosothiol groups per molecule than GSNO and might therefore be very useful as therapeutic agents. The aim of this study was to investigate the in vitro decomposition behaviour of SNOPCs under various physicochemical stress conditions and compare it to the decomposition behaviour of GSNO. SNOPCs were generally less stable than GSNO under all experimental conditions tested, which included exposure to light, variation of pH and temperature as well as exposure to different concentrations of exogenous free thiol in the form of reduced glutathione (GSH). Even under light exclusion at ambient temperature the SNOPCs retained only 40% of their intact SNO groups after a 48 h incubation time compared to 90% for GSNO. SNOPCs were also shown to readily take part in transnitrosation reactions when incubated with free glutathione. These properties suggest that SNOPCs could be employed as an investigation tool or possibly as therapeutic agents. (C) 2008 Elsevier Inc. All rights reserved.