Palladium Assisted Rapid Removal of a Solubilizing Tag from a Cys Side Chain to Facilitate Peptide and Protein Synthesis

Reversible attachment of solubilizing tags to hydrophobic peptides that are resistant to cleavage condition and yet removable from the final ligated product is an essential and challenging task in chemical protein synthesis in order to facilitate multiple purification and ligation steps. Herein we report on the efficient palladium-assisted removal of solubilizing tag linked to the Cys side chain. The strategy was applied for the efficient preparation of histone protein H4 from two fragments via one-pot operation of ligation, removal of solubilizing tag and desulfurization