Antioxidative Glutathione Peroxidase Activity of Selenoglutathione

摘要

Selenoglutathione (GSeH), a tripeptide comprising L-γ-glutamic acid (Glu), L-selenocysteine (Sec), and glycine (Gly), is a selenium analogue of glutathione (GSH), a biologically important redox substrate. This unique seleno-peptide is attracting increasing attention as it was recently demonstrated that the oxidized form, that is, GSeSeG (1), is useful for oxidative folding of disulfide(SS)-containing proteins, such as bovine pancreatic ribonuclease A (RNase A) and trypsin inhibitor (BPTI). Interestingly, diselenide 1 can even catalyze the folding reactions. Due to the structural similarity to oxidized glutathione (GSSG), it is also a possible substrate for glutathione reductase (GR), an enzyme that catalyzes reduction of GSSG with reduced nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor. Thus, GSeH and GSeSeG (1) are promising targets to explore their unique biological functions. We recently succeeded in synthesizing a Sec derivative, N-(9-fluorenylmethoxycar-bonyl)-Se-(p-methoxyphenylmethyl)-L-selenocysteine(Fmoc-Sec(MPM)-OH, 2) using L-cystine as a starting material. As an extension of our research, various Sec-containing peptides have now been synthesized from 2 by application of solid-phase peptide synthesis (SPPS), and their catalytic activity as an antioxidant has been investigated by employing the enzymatic assay of glutathione peroxidase (GPx), a well-known antioxidant selenoenzyme having a Sec residue at the redox-active site.