The issue of the influence of the side chain/backbone interaction on the local conformational preferences of a phenylalanine residue in a peptide chain is addressed. A synergetic approach is used, which combines gas-phase UV spectroscopy as well as gas-phase IR/UV double-resonance experiments with DFT and post Hartree-Fock calculations. N-Acetyl-Phe-amide was chosen as a model system for which three different conformers were observed. The most stable conformer has been identified as an extended L conformation of the peptide backbone. It is stabilized by a weak but significant NH- interaction bridging the aromatic ring on the residue (i) with the NH group on residue (i+1), with the aromatic side chain being in an anti conformation. This stable conformation corresponds to the common NH(i+1)-aromatic(i) interaction encountered in proteins for the three aromatic residues (phenylalanine, tyrosine, and tryptophan), which illustrates the relevance of gas-phase investigations to structural biology issues. The two other less abundant conformers have been assigned to two -folded backbone conformations that differ by the orientation of the side chain. In all cases, the IR data provided spectroscopic fingerprints of these interactions. Finally, the strong conformational dependence of the fluorescence yield found for N-acetyl-Phe-amide illustrates the role of the environment on the excited-state dynamics of these species, which is often exploited by biochemists to monitor protein structural changes from tryptophan lifetime measurements.
The Gas-Phase Dipeptide Analogue Acetyl-phenylalanyl-amide: A Model for the Study of Side Chain/Backbone Interactions in Proteins