An overview of peptide and peptoid foldamers in medicinal chemistry.

Introduction: Foldamers are artificial self-organizing systems with various critical properties: i) a stable and designable secondary structure; ii) a larger molecular surface as compared with ordinary organic drug molecules; iii) appropriate control of the orientation of the side-chain functional groups; iv) resistance against proteolytic degradation, which leads to potentially increased oral bioavailability and a longer serum half-life relative to ordinary α-peptides; and v) the lower conformational freedom may result in increased receptor binding in comparison with the natural analogs.

Areas Covered: This article covers the general properties and types of foldamers. This includes highlighted examples of medicinal chemical applications, including antibacterial and cargo molecules, anti-Alzheimer compounds and protein-protein interaction modifiers.

Expert Opinion: Various new foldamers have been created with a range of structures and biological applications. Membrane-acting antibacterial foldamers have been introduced. A general property of these structures is their amphiphilic nature. The amphiphilicity can be stationary or induced by the membrane binding. Cell-penetrating foldamers have been described which serve as cargo molecules, and foldamers have been used as autophagy inducers. Anti-Alzheimer compounds too have been created and the greatest breakthrough was attained via the modification of protein-protein interactions. This can serve as the chemical and pharmaceutical basis for the relevance of foldamers in the future.