Superfast Protein Desulfurization Triggered by Low‐Energy Visible Light

D Dongyang Han (New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Center for Synthetic and Systems Biology, Department of Chemistry) X Xiangyu Deng (New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Center for Synthetic and Systems Biology, Department of Chemistry) Y Yan Cui X Xianglai Zhu (New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Center for Synthetic and Systems Biology, Department of Chemistry) G Guiyu Deng (New Cornerstone Science Laboratory Tsinghua‐Peking Joint Center for Life Sciences MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology Center for Synthetic and Systems Biology Department of Chemistry Tsinghua University Beijing 100084 China) L Lu‐Jun Liang (Center for BioAnalytical Chemistry Hefei National Laboratory of Physical Science at Microscale University of Science and Technology of China Hefei 230026 China) G Guo‐Chao Chu (Division of Life Sciences and Medicine University of Science and Technology of China Hefei 230022 China) L Lei Liu

Abstract

Abstract The combination of transthioesterification‐based ligation of thiol‐derived amino acids and the post‐ligation desulfurization has greatly expanded the scope of modern chemical protein synthesis. Here, we report a new strategy of low‐energy visible light‐induced desulfurization (LEnVLD) that enables superfast and clean protein desulfurization (half life = 1.7 s) with improved reaction selectivity compared to the previous methods. The LEnVLD method can be easily carried out under very mild conditions using only a catalytic amount of fluorescent dye and household flashlight (ca. 5 W) irradiation, eliminating the need for any pyrophoric reagent, thiol additives, or excessive radical initiators, and its practicality was demonstrated by the fast and high‐yielding desulfurization of more than 30 peptide and protein substrates bearing a variety of sensitive functional groups (e.g., Thz, N‐alkylated maleimide, and thioester). Moreover, the convenience and robustness of LEnVLD enable its extension to versatile reaction scenarios (e.g., solid‐supported desulfurization and flow chemistry‐based desulfurization) that would enhance the practical capability of chemical protein synthesis.

Article Details

Volume / Issue Vol. 64, Issue 24
Published June 10, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (8)

D

Dongyang Han

New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Center for Synthetic and Systems Biology, Department of Chemistry

X

Xiangyu Deng

New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Center for Synthetic and Systems Biology, Department of Chemistry

Y

Yan Cui

X

Xianglai Zhu

New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Center for Synthetic and Systems Biology, Department of Chemistry

G

Guiyu Deng

New Cornerstone Science Laboratory Tsinghua‐Peking Joint Center for Life Sciences MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology Center for Synthetic and Systems Biology Department of Chemistry Tsinghua University Beijing 100084 China

L

Lu‐Jun Liang

Center for BioAnalytical Chemistry Hefei National Laboratory of Physical Science at Microscale University of Science and Technology of China Hefei 230026 China

G

Guo‐Chao Chu

Division of Life Sciences and Medicine University of Science and Technology of China Hefei 230022 China

L

Lei Liu