Solvent-induced β-hairpin to helix conformational transition in a designed peptide

Abstract

An octapeptide containing a central Aib-Gly- segment capable of adopting β-turn conformations compatible with both hairpin (β_II' or β_I′) and helical (β_I) structures has been designed. The effect of solvent on the conformation of the peptide Boc-Leu-Val-Val-Aib-Gly-Leu-Val-Val-OMe (VIII; Boc: t-butyloxycarbonyl; OMe: methyl ester) has been investigated by NMR and CD spectroscopy. Peptide VIII adopts a well-defined β-hairpin conformation in solvents capable of hydrogen bonding like (CD₃)₂SO and CD₃OH. In solvents that have a lower tendency to interact with backbone peptide groups, like CDCl₃ and CD₃CN, helical conformations predominate. Nuclear Overhauser effects between the backbone protons and solvent shielding of NH groups involved in cross-strand hydrogen bonding, backbone chemical shifts, and vicinal coupling constants provide further support for the conformational assignments in different solvents. Truncated peptides Boc-Val-Val-Aib-Gly-Leu-Val-Val-OMe (VII), Boc-Val-Val-Aib-Gly-Leu-Val-OMe (VI), and Boc-Val-Aib-Gly-Leu-OMe (IV) were studied in CDCl₃ and (CD₃)₂SO by 500 MHz ¹H-NMR spectroscopy. Peptides IV and VI show no evidence for hairpin conformation in both the solvents. The three truncated peptides show a well-defined helical conformation in CDCl₃. In (CD₃)₂SO, peptide VII adopts a β-hairpin conformation. The results establish that peptides may be designed, which are poised to undergo a dramatic conformational transition.