Studies on the Synthesis and Properties of the Mimics with Glutathione Peroxidase Activity and Preparation of the Conjugate of Mimic-Antibody

Glutathione peroxidase (EC 1.11.1.9, GSH-Px) catalyzes the reduction of a wide variety of hydroperoxides, it together with GSH1 constitutes a powerful cellular defence system against so-called oxidative damage [1]. As enzyme protein may not readily reach intracellular target site, the therapeutic use of GSH-Px as a tetrameric enzyme could be limited in systemic application. It is therefore of interest to study the reactivity of a low molecular weight compound which contains some of the features of the enzyme’s active site. The active site of GSH-Px is composed of a selenocysteinyl residue surrounded by aromatic amino acids which are involved in the enzymic reaction. On the basis of the properties of the active site of GSH-Px, we have designed and synthesized three organoselenium compounds (II, III, and IV), which exhibit GSH-Px-like activity. In order to develop the use of the mimic in clinical therapy we have prepared a conjugate of mimic (IV) with anti-human IgG (Fcr).