Evolution of Helical Foldamers

The overwhelming majority of unnatural foldamers described so far adopt various helical conformations. Helical foldamers include peptidomimetic oligomers such α-, β- and γ-peptides, and non-biological helices such as helicates, oligoheterocycles and olio(phenylene ethynylenes). Lying between peptidomimetic and non-biological foldamers are oligoarylamides whose backbones are rigidified by strong intramolecular hydrogen bonds. The localized nature of the intramolecular hydrogen bonds allows structure the tuning of both the side chains and the curvature of the backbones, leading to helices of different surface properties and tunable interior cavities. As a result, hollow helices with interior channels of tunable, finite diameters are generated. Thus, unnatural helical foldamers have evolved from providing examples of stably folded secondary structures to demonstrating features of higher structural levels of biomacromolecules, e.g., the creation of nanocavities.