Helices in peptoids of α- and β-peptides

Peptoids of α- and β-peptides (α- and β-peptoids) can be obtained by shifting the amino acid side chains from the backbone carbon atoms of the monomer constituents to the peptide nitrogen atoms. They are, therefore, N-substituted poly-glycines and poly-β-alanines, respectively. Due to the substituted nitrogen atoms, the ability for hydrogen bond formation between peptide bonds gets lost. It may be very interesting to see whether such non-natural oligomers could be regarded as foldamers, which fold into definite backbone conformers. In this paper, we provide a complete overview on helix formation in α- and β-peptoids on the basis of systematic theoretical conformational analyses employing the methods of ab initio molecular orbital (MO) theory. It can be shown that the α- and β-peptoid structures form helical structures with both trans and cis peptide bonds despite the missing hydrogen bonds. Obviously, the conformational properties of the backbone are more important for folding than the possibility of hydrogen bonding. There are close relationships between the helices of α-peptoids and poly-glycine and poly-proline helices of α-peptides, whereas the helices of β-peptoids correspond to the well-known helical structures of β-peptides as, for instance, the 3₁-helix of β-peptides with 14-membered hydrogen-bonded rings. Thus, α- and β-peptoids enrich the field of foldamers and may be used as useful tools in peptide and protein design.