Gas Phase Formation of a 310-Helix in a Three-Residue Peptide Chain: Role of Side Chain-Backbone Interactions as Evidenced by IR−UV Double Resonance Experiments

Abstract

The first spectroscopic evidence for the gas-phase formation of helical structures in short peptide chains is reported, using the IR-UV double resonance technique and DFT quantum chemistry calculations. The study involves three chemically protected peptides, all based on the same Ac-(Ala)3-NH2, (Ac = acetyl, Ala = alanine) tripeptide, in which one of the Ala residues is substituted by the aromatic phenylalanine residue. For the three molecules, only one main conformer is observed in the supersonic expansion. IR analysis shows that the structure of this conformer is strongly dependent upon the substitution site: the helical 310-type structure is observed only when Phe occupies the central residue of the chain. The present work also emphasizes that the 310-helix formation does compete with other archetypal H-bonding patterns, such as 27-ribbon or mixed structures, whose relative energetics can be greatly influenced by a modest NH-aromatic interaction.