Crystal structure analysis of helix–turn–helix type motifs in α,γ-hybrid peptides†

Mimicking protein supersecondary structures using short synthetic peptide sequences holds significant importance in the fields of synthetic protein design, catalysis, and drug discovery. In this study, we present a series of helix–turn–helix motifs derived from short α,γ-hybrid peptides, incorporating centrally positioned E-α,β-unsaturated γ-amino acids. By varying the number of trans double bonds at the central residue, the positioning of the helices can be adjusted. Superimposing the synthetic seven-residue helix–turn–helix motif with the natural calcium-binding helix–turn–helix motif revealed the potential to design three-dimensional helix–turn–helix motifs within short peptide sequences.