The chemical synthesis of peptides and proteins is useful to obtain products that are difficult to obtain by protein expression in living cells. Native chemical ligation (NCL), for example, involves coupling reactions between two unprotected peptides, one with a C-terminal thioester and one with an N-terminal cysteine. However, this means that the product scope is limited by the required cysteine residue. Desulfurization reactions that convert cysteine to alanine after ligation can be used to work around this limitation.
Lu-Jun Liang, University of Science and Technology of China, Hefei, Lei Liu, Tsinghua University, Beijing, China, and colleagues have developed an easy-to-use, ultrasound-induced protein desulfurization strategy (USID) that is generally applicable to peptides and proteins. The team used an ultrasonic cleaning bath to treat buffered solutions of peptides/proteins, and improved the efficiency of the reactions using titanium dioxide nanoparticles as a sonosensitizer.
Under these conditions, desulfurized products were formed in high yields. The method showed good functional group tolerance, with groups such as biotin or acetamidomethyl remaining unchanged. Multiple cysteine residues within peptides or proteins could be simultaneously desulfurized.
- Mechanically Triggered Protein Desulfurization,
Dongyang Han, Yan Cui, Xiangyu Deng, Chuntong Li, Xianglai Zhu, Bingji Wang, Guo-Chao Chu, Zhipeng A. Wang, Shan Tang, Ji-Shen Zheng, Lu-Jun Liang, Lei Liu,
J. Am. Chem. Soc. 2025.
https://doi.org/10.1021/jacs.4c13464
