Development of an efficient method for N-terminal alpha-amino group ligation of peptides in aqueous medium

ORGN 530

Man-Kin Wong, mkwong@hkusua.hku.hk, Wing-Kei Chan, Chi-Ming Ho, and Chi-Ming Che, cmche@hku.hk. Chemistry Department & Open Lab of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam Road, Hong Kong, China
Selective modification of amino groups is of great importance in bioconjugation. Successful development of efficient methods for N-terminal alpha-amino group ligation of peptides would facilitate bioconjugate synthesis, positional proteomics studies and peptide microarray fabrication. However, it remains a significant challenge to selectively modify the N-terminal alpha-amino group of unprotected peptides with other nucleophilic side chain residues, such as the lysine amino group remaining intact. Here we report an efficient method for selective N-terminal alpha-amino group ligation of unprotected peptides in aqueous medium via oxidative coupling of alkynes with amines using manganese porphyrins as catalysts and hydrogen peroxide as the terminal oxidant. Mechanistic studies suggested that ketene generated from alkyne oxidation is a key intermediate for the coupling reaction. Currently, we are expanding the scope of this bioconjugation reaction.