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An efficient thiol-assisted one-pot synthesis of peptide/protein C-terminal thioacids was achieved by using peptide/protein hydrazides precursors at neutral pH and room temperature (about 20 °C). The transformation from hydrazides to thioacids was shown to be efficient for different C-terminal amino acids and was racemization-free. The in situ formed peptide-thioacids were further used for protein chemical synthesis and site-specific labelling successfully.

Graphical abstract: Thiol-assisted one-pot synthesis of peptide/protein C-terminal thioacids from peptide/protein hydrazides at neutral conditions

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