Helix Formation in α,γ- and β,γ-Hybrid Peptides: Theoretical Insights into Mimicry of α- and β-Peptides

Publisher Website
Google Scholar
Abstract
α,γ- and β,γ-hybrid peptides, which are composed of two different homologous amino acid constituents in alternate order, are suggested as novel classes of peptide foldamers. On the basis of a systematic conformational search employing the methods of ab initio MO theory, the possibilities for the formation of periodic secondary structures in these systems are described. The conformational analysis provides a great number of helix conformers widely differing in energy, which can be arranged into three groups: (i) helices with all hydrogen bonds formed in forward direction along the sequence, (ii) helices with all hydrogen bonds in backward direction, and (iii) helices with alternate hydrogen-bond directions (mixed or β-helices). Most stable are representatives of β-helices, but their stability decreases considerably in more polar environments in comparison to helix conformers from the other two classes. There is a great similarity between the overall topology of the most stable hybrid peptide helices and typical helices of peptides which are exclusively composed of a single type of homologous amino acids. Thus, the helices of the β,γ-hybrid peptides mimic perfectly those of the native α-peptides as, for instance, the well-known α-helix, whereas the most stable helix conformers of α,γ-hybrid peptides correspond well to the overall structure of β-peptide helices. The two suggested novel hybrid peptide classes expand considerably the pool of peptide foldamers and may be promising tools in peptide design and in material sciences.

This publication has 84 references indexed in Scilit: