2.5.3. Secondary structure

Because the backbones of β-peptides are longer than those of α-peptides, β-peptides form different secondary structures. The alkyl substituents at both the α- and β-positions in a β-amino acid favor a gauche conformation about the bond between the α-carbon and β-carbon. This also affects the thermodynamic stability of the structure.

2.5.3.1. The Helices of β-Peptides
Many types of helix structures consisting of β-peptides have been reported. These conformation types are distinguished by the number of atoms in the hydrogen-bonded ring that is formed in solution; 8-helix, 10-helix, 12-helix, 14-helix, and 10/12-helix have been reported. In general, β-peptides form a more stable helix than α-peptides.
A comparative structural analysis of an a-peptide 3.6₁ helix with the 3₁ and 2.5₁ helices of b-peptides shows the following informations: (a) the helices have different polarities with respect to their C and N-termini; (b) their shapes and sizes drastically are different; (c) the 3₁ β-peptide helix can be produced with the homochiral residues or with the residues having 2,3-l relative configuration; (d) the 3₁ β-peptide helix can be produced with geminal disubstitution, however, the α-helix is stabilized by incorporation of geminally disubstituted α-amino acids; (e) the β-peptide helices are stabilized by hydrophobic interactions between side chains. The hydrophobic interactions contribute a lot to make a difference between β²- and β³-peptides (3₁ helix) and the mixed β²-/β³-peptides.

Figure 2.28:A comparative structures of a α-peptide helix with β-peptides helices.

Figure 2.29:β-peptides helices show the β-amino acids residues.

Figure 2.30: Helices with 4 → 1 hydrogen-bond patterns in α, β, and αβ-hybrid peptides.

Figure 2.31:  Helix bundle β, and ab-hybrid peptides. (a) Molecular conformation of a b³-dodecapeptide 14-helix in H₂N- βGlu-βLeu-βOrn-βPhe-βLeu-βAsp-βPhe-βLeu-βOrn-βOrn-βLeu-βAsp-OH. (b) Conformation of a αβ-hybrid peptide with the sequence repeat αααβ. This is derived from a 33 residue α-peptide of the dimerization domain of yeast transcriptional regulator.