Hmb(off/on) as a switchable thiol protecting group for native chemical ligation.
A new thiol protecting group Hmb(off/on) is described, which has a switchable activity that may be useful in the chemical synthesis of proteins. When placed on the side chain of Cys, Cys(Hmb(off)) is stable to trifluoroacetic acid (TFA) in the process of solid-phase peptide synthesis. When Cys(Hmb(off)) is treated with neutral aqueous buffers, it is cleanly converted to acid-labile Cys(Hmb(on)), which can later be fully deprotected by TFA to generate free Cys. The utility of Cys(Hmb(off/on)) is demonstrated by the chemical synthesis of an erythropoietin segment, EPO[Cys(98)-Arg(166)]-OH through native chemical ligation.
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China. lliu@mail.tsinghua.edu.cn and High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China. jszheng@hmfl.cas.cn.
Yun-Kun
YK
Qi
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China. lliu@mail.tsinghua.edu.cn.
Shan
S
Tang
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China. lliu@mail.tsinghua.edu.cn.
Yi-Chao
YC
Huang
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China. lliu@mail.tsinghua.edu.cn.
Man
M
Pan
High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China. jszheng@hmfl.cas.cn.
Ji-Shen
JS
Zheng
Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China. lliu@mail.tsinghua.edu.cn.
Lei
L
Liu
D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D010455:Peptides; D013438:Sulfhydryl Compounds