One-pot iterative native chemical ligation–desulfurisation chemistry leveraging a coumarin-based photolabile protecting group for cysteine

An iterative one-pot peptide native chemical ligation (NCL)–desulfurisation strategy, featuring 7-diethylamino-3-methyl coumarin (DEAMC) as an orthogonal protecting group for cysteine, is described. We show that selective desulfurisation of unprotected cysteine residues can be achieved in the presence of DEAMC-protected cysteine residues, allowing subsequent DEAMC photodeprotection and native chemical ligation to be performed without purification. The efficiency of this approach was exemplified through the one-pot synthesis of a 60-residue mucin-1 peptide.