Development of efficient methods for accomplishing cysteine-free peptide and glycopeptide coupling

As simple as A, B, C: Non-cysteine-based reiterative fragment coupling of glycopeptides involves a metal-free (TCEP) coupling of a peptidyl C-terminal phenolic ester containing an ortho-disulfide moiety (A) with an N-terminal glycopeptide whose C terminus is an alkyl thioester (B) to produce AB, whose N terminus contains an alkyl thioester. A AgCl-mediated coupling of AB with peptide C then produces the tridomainal peptide ABC. TCEP = tris (2-carboxyethyl)phosphine. (Chemical Equation Presented)