Abstract
Sequence diversification at the C terminus is traditionally limited by significant epimerization of the C-terminal residue during its activation toward nucleophilic attack, thus mandating repetition of the peptide synthesis for each targeted variation. Here, we accomplish divergent C-terminal elongation of a single peptide substrate with concomitant resin cleavage via displacement of an N-acyl urea moiety. Sterically hindered amino acids such as Ile and Pro are well-tolerated in this approach, which proceeds reasonable conversion and no detectable epimerization of the starting peptide's C-terminal amino acid.