Gene Manipulation Based Selenium-containing Peptide Exhibiting Synergism of SOD and GPx

In this paper, we constructed a novel bifunctional superoxide dismutase(SOD)/glutathione peroxi- dase(GPx) mimic, a selenium-, copper-containing 35-mer peptide conjugate(Se-Cu-35P) in which a three-amino acid linker(Gly-Asn-Gly) connects the C-terminus of 17-mer polypeptide SOD mimic with the N-terminus of 15-mer polypeptide GPx mimic. The SOD and GPx activities of Se-Cu-35P are two orders of magnitude lower than those of natural SOD and GPx, respectively. It provides a GPx activity 56-fold higher than Ebselen(a well-known GPx mimic). The glutathione(GSH) binding constant is 5.6×10² L·mol^-1. Se-Cu-35P synergistically resists against the inactivation by H₂O₂ and protects the mitochondria from oxidative damage in a dose dependent manner. These results highlight the challenge of generating an efficient SOD/GPx synergism mimic. It could facilitate the studies of the cooperation of GPx and SOD and could be a potential therapeutic agent for the treatment of ROS-mediated diseases.