Correlating the GPx Activity of Selenocystine Derivatives with One-Electron Redox Reactions

Abstract

With an aim to develop water soluble, less toxic glutathione peroxidase (GPx) mimics, three selenocystine (SeCys) derivatives, viz., selenocystamine (SeA), diselenodipropionic acid (SeP), and methyl ester of diselenodipropionic acid (MeSeP) have been synthesized and examined for GPx activity along with SeCys. The GPx activity of the compounds was found to be in the order SeCys ≅ SeA > MeSeP > SeP. The relative affinity of these GPx mimics towards the substrates thiol and hydroperoxide were determined by Lineweaver-Burk (L-B) plots. Since the enzyme activity involves several steps of reduction and oxidation reactions, attempts have been made to understand the role of such processes in deciding the efficacy of diselenides as GPx mimics. For this, one-electron redox chemistry of these compounds was studied in aqueous solutions at pH 7 using nanosecond pulse radiolysis technique. From these studies, it was concluded that SeCys and SeA, which can undergo easy one-electron reduction, exhibit high GPx activity.

Keywords:

• Selenocystine
• diselenides
• GPx activity
• pulse radiolysis
• redox reactions