Abstract:

The ability to chemically synthesize and modify biomacromolecules with atomic-level precision has opened up new opportunities for discovering fundamental chemical biology and developing novel therapeutic modalities. Especially, desulfurization chemistry has been successfully used to expand the dimension of chemical protein synthesis with cysteine-based peptide ligation technology. This report presents a new reactivity of an old reagent, sodium tetraethylborate (NaBEt₄), which performs a superfast and easy-to-use desulfurization for peptides and proteins. Compared to previous methods with complicated operations, this strategy can be simply applied at ambient conditions without needing an inert atmosphere, irradiation, heating, or exogenous thiol additives. This add-and-done desulfurization can overcome a certain amount of radical scavenger. The efficiency of this strategy has been demonstrated with various peptide and protein substrates, and an efficient one-pot native chemical ligation (NCL)-desulfurization strategy has also been developed for the successful chemical synthesis of leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) cytoplasmic domain and the semisynthesis of serotonylated histone H3Q5ser.

References
[1] Sun, Z.; Ma, W.; Cao, Y.; Wei, T.; Mo, X.; Chow, H.Y.; Tan, Y.; Cheung, C.H.P; Liu, J.; Lee, H.K.; Tse, E.C.M; Liu, H.; Li, X. Chem 2022, 8: 2543-2557.
[2] Sun, Z.; Wei, T.; Cao, Y.; Li, X. STAR Proctoc. 2023, 4: 102042.

Acknowledgement: This work was supported by the Research Grants Council of University Grants Committee of Hong Kong (C7147-20G, 17303920, 17302621, AoE/P-706/16).