Peptidomimetic design of unusual turns by incorporating flexible and rigid ω-amino acids simultaneously

The tripeptides Boc-Gly-Aib-m-ABA-OMe (I), Boc-βAla-Aib-m-ABA-OMe (II) and Boc-γAbu-Aib-m-ABA-OMe (III) (Aib: α-aminoisobutyric acid, βAla: β-alanine, γAbu: γ-aminobutyric acid, m-ABA: meta-aminobenzoic acid) with homologated amino acids at the N-terminus, the rigid γ-amino acid m-ABA at the C-terminus and the helicogenic Aib at the central position have been chosen to create unusual turns. Single crystal X-ray diffraction studies, solvent dependent NMR titrations and 2D NMR analysis reveal that peptides II and III adopt unusual turns of 11- and 12-membered rings stabilized by modified 4 → 1 type intramolecular hydrogen bonds. Solution phase studies indicate that peptide I exists in the β-turn conformation stabilized by 10-membered intramolecular hydrogen bonding.