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（（31y-Asn-Gly） connects the C-terminus of 17-mer polypeptide SOD mimic with the N-terminus of 15-mer po- lypeptide 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× 10^2 L.mol 1. Se-Cu-35P synergistically resists against the inactivation by H202 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,