Folding and function in α/β-peptides: targets and therapeutic applications

Combining natural α-amino acid residues and unnatural β-amino acid residues in a single chain leads to heterogeneous-backbone oligomers called α/β-peptides. Despite their unnatural backbones, α/β-peptides can manifest a variety of folding patterns and biological functions reminiscent of natural peptides and proteins. Moreover, incorporation of β-residues can impart useful properties to the oligomer such as improved stability to degradation by protease enzymes. α/β-Peptides have been developed that engage diverse biological targets, including proteins involved in apoptotic signalling, HIV-cell fusion, hormone signalling, and angiogenesis. For some systems, promising results obtained in vitro have paved the way for demonstrated activity in vivo, where α/β-peptides show equal potency and improved duration of effect compared to α-peptide counterparts.