TOTAL CHEMICAL SYNTHESIS OF HUMAN SELENOPROTEIN M

The human selenoproteome consists of 25 selenoproteins, yet approximately a dozen awaits functional characterization. Of those, seven are located in the endoplasmic reticulum (ER). One such protein, selenoprotein M (SelM), has been suggested to take part in protein folding due to its location in the ER. SelM belongs to the thiol-disulfide oxidoreductase superfamily, exhibiting a similar three-dimensional structure and an active site motif C-X-X-U, in which selenocysteine (Sec, U) replaces the second cysteine (Cys, C) in the thiol-based enzyme counterparts. SelM is expressed in many tissues in the body, but is most abundant in the brain, which may suggest an important role in the nervous system. In spite of numerous investigations, the exact function of SelM has not been fully elucidated, mainly due to challenges in preparing large quantities of selenoproteins recombinantly and in homogeneous forms. Our research goal is to prepare sufficient workable amounts of this protein for biological studies. Here we present a synthetic scheme for mature human SelM using solid-phase peptide synthesis and native chemical ligations (NCL). Upon completion of this goal, the antioxidant activity of SelM and its function in oxidative protein folding will be studied.