A novel glutathione peroxidase mimic with antioxidant activity

Many diseases are associated with the overproduction of hydroperoxides that inflict cell damage. A novel cyclodextrin derivative, 6A,6B-diseleninic ac id-6A ' ,6B ' -selenium bridged beta -cyclodextrin (6-diSeCD), was synthesi zed to be a functional mimic of glutathione peroxidase (GPX) that normally removes these hydroperoxides. The mimic had high catalytic GPX activity of 13.5 U/mu mol, which is 13.6-fold higher than ebselen (PZ51), and was chemi cally and biologically stable in vitro. Antioxidant activity was studied by ferrous sulfate/ascorbate-induced mitochondria damage model system. These data show that the mimic has great antioxidant activity. Such mimics may re sult in better clinical therapies for diseases mediated by hydroperoxides. (C) 2001 Academic Press.