Dery L, Reddy P Sai, Dery S, Mousa R, Ktorza O, Talhami A, Metanis N
Institute of Chemistry , The Hebrew University of Jerusalem , Edmond J. Safra, Givat Ram , Jerusalem 91904 , Israel . Email:
Chem Sci. 2017 Mar 1;8(3):1922-1926. doi: 10.1039/c6sc04123j. Epub 2016 Nov 1.
The human body contains 25 selenoproteins, which contain in their sequence the twenty-first encoded amino acid, selenocysteine. About a dozen of these proteins remain functionally uncharacterized or poorly studied. Challenges in accessing these selenoproteins using traditional recombinant expressions have prevented biological characterization thus far. Chemical protein synthesis has the potential to overcome these hurdles. Here we report the first total chemical syntheses of two human selenoproteins, selenoprotein M (SELM) and selenoprotein W (SELW). The synthesis of the more challenging protein SELM was enabled using recent advances in the field of selenocysteine chemistry. This approach allows the preparation of selenoproteins in milligram quantities and in homogenous form, which should open new horizons for future studies to pursue a fuller biological understanding of their role in health and disease.
人体含有25种硒蛋白，其序列中包含第21种编码氨基酸——硒代半胱氨酸。其中约有十二种蛋白质的功能尚未明确或研究较少。迄今为止，使用传统重组表达方法获取这些硒蛋白面临的挑战阻碍了其生物学特性的鉴定。化学蛋白质合成有潜力克服这些障碍。在此，我们报告了两种人类硒蛋白——硒蛋白M（SELM）和硒蛋白W（SELW）的首次全化学合成。利用硒代半胱氨酸化学领域的最新进展实现了更具挑战性的蛋白质SELM的合成。这种方法能够以毫克量制备出均一形式的硒蛋白，这应为未来研究开启新的视野，以便更全面地从生物学角度了解它们在健康和疾病中的作用。
