CHAPTER 3. Peptide Engineering Strategies

Over the past two decades, significant efforts have been invested in developing strategies to stabilize the α-helix structure of macrocyclic peptides by stapling their architectures. These strategies can be divided into two categories: side chain to side chain cross-linking and N-terminal helix nucleation. These stable macrocyclic peptides have been applied in proton pump inhibitors and self-assembly materials. Compared with unmodified short peptides, stable α-helix macrocyclic peptides have better biophysical properties, such as higher serum stability, better cell permeability and higher target affinity. This chapter will systematically introduce helical stabilization approaches for peptides, such as ring-closing metathesis, lactamisation, cycloadditions, reversible reactions, thioether formation and sulfonium center formation. Thereafter, the applications of helical stabilized peptide-based materials are discussed and presented with a view to encourage various translations for peptides.