Superfast desulfurization for protein chemical synthesis and modification

Abstract

Highly effective yet chemoselective chemical transformation strategies enable the facile access and precise modification of complicated biomacromolecules. In particular, the application of desulfurization chemistry expands the dimension of chemical protein synthesis with the cysteine-based peptide ligation. Considering the existing peptide desulfurization methods, a milder, faster, and easier strategy is still required for the increasing complexity of proteins by chemical synthesis. Herein, we report a superfast desulfurization strategy based on tetraethylborate for effectively and chemoselectively desulfurizing peptides/proteins containing cysteine or penicillamine in an add-and-done manner. This strategy can be simply applied under ambient conditions without requirement of inert atmosphere protection, irradiation, heating, or exogenous thiol additives. Such desulfurization can even overcome a certain amount of radical scavengers. Various peptide and protein substrates were examined, and a practical one-pot native chemical ligation (NCL)-desulfurization was developed for the synthesis of leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) cytoplasmic domain and semisynthesis of serotonylated histone H3 (H3Q5ser) protein.