Hybrid helices: motifs for secondary structure scaffolds in foldamers.

The concept of "hybrid helices" as a new motif for foldamers is presented. Hybrid helices can be realized by a combination of two or more different types of homologous and hybrid peptides, for example, beta-peptides and alpha/beta- and alpha/gamma-hybrid peptides, within the same oligomer. The different helix types of the various peptide foldamer classes are maintained and form a regular helix along the sequence of the oligomer. The transition from one helix type to another was found to be rather smooth with high compatibility of the different helix types. Such hybrid helices represent novel motifs of secondary structure scaffolds. They open up the possibility to change the direction of helix propagation in a subtle manner. Hybrid helices enrich the arsenal of defined foldamer structures for a structural and functional mimicry of native peptides and proteins.