Citation: Min Fu, Ruihan Wang, Wenqiang Liu, Sen Zhou, Chunhong Zhong, Yaohao Li, Pan He, Xin Li, Shiying Shang, Zhongping Tan. Improved one-pot protein synthesis enabled by a more precise assessment of peptide arylthioester reactivity[J]. Chinese Chemical Letters, ;2025, 36(7): 110542. doi: 10.1016/j.cclet.2024.110542 shu

Improved one-pot protein synthesis enabled by a more precise assessment of peptide arylthioester reactivity

Min Fu ^a ,
Ruihan Wang ^{a, b} ,
Wenqiang Liu ^a ,
Sen Zhou ^a ,
Chunhong Zhong ^a ,
Yaohao Li ^a ,
Pan He ^a ,
Xin Li ^a ,
Shiying Shang ^c ,
Zhongping Tan ^{a, *,}

a.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
b.
Chemical Engineering College, Hebei Normal University of Science and Technology, Qinhuangdao 066600, China
c.
Center of Pharmaceutical Technology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China

zhongping.tan@imm.ac.cn

Received Date: 25 July 2024
Revised Date: 23 September 2024
Accepted Date: 9 October 2024
Available Online: 11 October 2024

Figures(6)

By investigating 17 peptide arylthioesters that were previously challenging to produce, this study reveals a clear correlation between increased ligation activity and decreased pKa values of their corresponding arylthiols. The observed differences are attributed to variations in thioester bond strength and steric hindrance. These insights have led to the development of an improved one-pot chemical protein synthesis approach that leverages the reactivity differences between peptide arylthioesters with C-terminal Ala-S-Ph(4-NO₂) and Ala-S-Ph(2,6-diCH₃). This approach eliminates the need for thiol-thioester exchange and additive removal steps while enabling in situ desulfurization, thereby significantly simplifying the protein synthesis process.
- Chemical protein synthesis,
- Arylthioesters,
- One-pot synthesis,
- Native chemical ligation,
- In situ desulfurization
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