Review on the o-Aminoaniline Moiety in Peptide and Protein Chemistry

Peptides and proteins are important functional biomolecules both inside and outside of living organisms. The ability to prepare various types of functionalized peptides and proteins is essential for understanding fundamental biological processes, such as protein folding and post-translational modifications (PTMs), and for developing new therapeutics for many diseases, such as cancers and neurodegenerative diseases. The o-aminoaniline moiety was first proposed for activation to a thioester precursor and used for native chemical ligation to prepare large peptides and proteins. In the past decade, the function of o-aminoaniline has been greatly expanded to facilitate the preparation of homogeneously modified peptide and protein samples, where the modifications can include cyclization, C-terminus diversification, etc. Many o-aminoaniline derivatives have also been developed to overcome the inherent limitations of previous versions. In this review, we attempt to summarize the recent developments of different o-aminoaniline derivatives, focusing on their application to the preparation of functional peptide and protein molecules.