Chemoselective coupling of peptide fragments using the Staudinger ligation

Here we report the first Staudinger ligations which yield tetra- and pentapeptides starting from N-terminal α-azido peptides and C-terminal peptide o-(diphenylphosphine)phenyl esters. Mass spectrometric analysis of the reaction mixture provided a better insight into the mechanism of the Staudinger ligation and has been used to explain the observed intermediates and to optimize the ligation reaction. As a result, the optimized reaction enables the chemoselective coupling of peptides containing amino acids other than glycine at the ligation site.