Chemical synthesis of human selenoprotein F and elucidation of its thiol-disulfide oxidoreductase activity |
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| Authors: | Peisi Liao Hongmei Liu Chunmao He |
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| Affiliation: | School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640 China.; Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074 China.; Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen 518057 China |
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| Abstract: | Selenoprotein F (SelF) is an endoplasmic reticulum-residing eukaryotic protein that contains a selenocysteine (Sec) residue. It has been suggested to be involved in a number of physiological processes by acting as a thiol-disulfide oxidoreductase, but the exact role has remained unclear due to the lack of a reliable production method. We document herein a robust synthesis of the human SelF through a three-segment two-ligation semisynthesis strategy. Highlighted in this synthetic route are the use of a mild desulfurization process to protect the side-chain of the Sec residue from being affected and the simultaneous removal of acetamidomethyl and p-methoxybenzyl protection groups by PdCl2, thus facilitating the synthesis of multi-milligrams of homogenous SelF. The reduction potential of SelF was determined and the thiol-disulfide oxidoreductase activity was further supported by its ability to catalyze the reduction and isomerization of disulfide bonds.The chemical synthesis of the 134-residue human selenoprotein F (SelF) was accomplished on a multi-milligram scale. The synthetic SelF exhibits typical thiol-disulfide oxidoreductase activity. |
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