Peptide Ligations at Sterically Demanding Sites

Chemical synthesis of proteins and polypeptides is a valuable strategy to generate pure and homogeneous primary structures of natural or modified proteins and their analogues. In most of the synthesis ligation of peptide segments is required, which has been extensively studied for amide bond formations at most amino acid sites. However, peptide ligation at sterically demanding C-termini of peptides, such as β-branched amino acids and cyclic proline, remains a challenge. Additionally, the diverse sequences of various proteins call for solutions to overcome the low efficiency issues of ligating peptides at those difficult junction sites. In this review, we briefly overview the recent development on new strategies that aim to address these issues in peptide ligations and line out representative examples of their applications in protein chemical synthesis.