An efficient peptide ligation using azido-protected peptides via the thioester method

Azido-protected Fmoc–Lys–OH (Fmoc–Lys(N3)–OH) was synthesized from Fmoc–Lys–OH by the copper(II)-catalyzed diazo transfer method, and introduced to a peptide by the ordinary Fmoc-based solid-phase peptide synthesis. This azido peptide could be condensed with a peptide thioester by the Ag+-free thioester method without any significant side reactions. The azido group was easily reduced to an amino group by Zn powder after peptide condensation.