Stable Right- and Left-Handed Peptide Helices containing C^α-Tetrasubstituted α-Amino Acids

Short peptidomimetics with stable secondary structures in solution are of interest for applications in chemistry, biology, and medicine. One way to rigidify the backbone of a peptide is the use of cyclic C^α-tetrasubstituted α-amino acids (TAAs) like compound 14. The structures resulting from the incorporation of this unnatural amino acid into peptides were investigated. In total, 13 different peptides with a length of up to eight residues and alternating sequences of TAA 14 and (S)- or (R)-valine were synthesized. Their structures were characterized by X-ray diffraction analysis and NMR and CD measurements showing that the all-S-backbone-configured peptides 5 and 6 (SS)₂₋₃ form right-handed 3₁₀-helices, while the all-R-configured peptides 11−13 (RR)₂₋₄ form left-handed 3₁₀-helices in the solid state and solution.