Secondary structures of short peptide chains in the gas phase:  Double resonance spectroscopy of protected dipeptides

Abstract

The conformational structure of short peptide chains in the gas phase is studied by laser spectroscopy of a series of protected dipeptides, Ac-Xxx-Phe-NH 2 , XxxϭGly, Ala, and Val. The combination of laser desorption with supersonic expansion enables us to vaporize the peptide molecules and cool them internally; IR/UV double resonance spectroscopy in comparison to density functional theory calculations on Ac-Gly-Phe-NH 2 permits us to identify and characterize the conformers populated in the supersonic expansion. Two main conformations, corresponding to secondary structures of proteins, are found to compete in the present experiments. One is composed of a doubly ␥-fold corresponding to the 2 7 ribbon structure. Topologically, this motif is very close to a ␤-strand backbone conformation. The second conformation observed is the ␤-turn, responsible for the chain reversal in proteins. It is characterized by a relatively weak hydrogen bond linking remote NH and CO groups of the molecule and leading to a ten-membered ring. The present gas phase experiment illustrates the intrinsic folding properties of the peptide chain and the robustness of the ␤-turn structure, even in the absence of a solvent. The ␤-turn population is found to vary significantly with the residues within the sequence; the Ac-Val-Phe-NH 2 peptide, with its two bulky side chains, exhibits the largest ␤-turn population. This suggests that the intrinsic stabilities of the 2 7 ribbon and the ␤-turn are very similar and that weakly polar interactions occurring between side chains can be a decisive factor capable of controlling the secondary structure.

Isolated Neutral Peptides

“…3.3). Vibrational couplings make the interpretation less easy, and confident assignments rely on a large spectral range (the whole amide I-III regions), especially when spectral resolution is limited, usually 1% of the IR frequency for a freeelectron source [48,54,55,66,69,79,80,82,83,95,97,105,108,131,132,136,141,142]. Difference frequency generation from table-top OPOs [52,64,90,104,120,126,127,137,139,144,145] has become a valuable alternative source to FELs, providing spectral resolutions in the cm À1 range, and solid conformational assignments have emerged from studies combining amide I/II and amide A spectral ranges (Fig.…”

“…Namely, aromatic-aromatic [103,111,112] or aromatic-alkyl [82,94] interactions not only shape the molecule but also impact the conformational landscape by significantly changing the relative conformational energetics. Unfortunately, because of the lack of workable vibrational probe on these groups, these major interactions are only remotely detected through the constraints they bring to the regions where the vibrational probes lie [103].…”

“…The comparison between isolated features and the same feature embedded in a more or less complex H-bond network enables one to document the existence of cooperative electronic effects, presumably caused by an electronic polarisation of the amide groups favoured by the H-bond network, especially when a circular chain is formed [82,107,121,134,139]. As expected for a vibrational motion coupled to the rest of the molecules, the linewidth associated with these coupled oscillators is often significantly broadened compared to the poorly coupled oscillators such as those engaged in a C5 interaction.…”

Towards the Determination of the Absolute Configuration of Complex Molecular Systems: Matrix Isolation Vibrational Circular Dichroism Study of (R)‐2‐Amino‐1‐propanol

“…(Recent examples include evaporated small model peptides. [16][17][18] ) Moreover, in contrast to gas-phase measurements, the matrix-isolation technique has the advantage that (assuming a perfect vacuum seal) the sample stream can be arbitrarily slow-only the noble-gas stream and the deposition time have to be adjusted. Computational costs are continuously decreas- ing; furthermore, parallel and hybrid quantum-mechanical/ molecular-mechanical codes could be used to calculate VCD spectra.…”

Molecular and supramolecular chirality: R2PI spectroscopy as a tool for the gas‐phase recognition of chiral systems of biological interest

“…Precious structural information has been gathered on biologically relevant chiral molecules, such as neurotransmitters, 35,[77][78][79][80] amino acids, 81,82 small peptides, [83][84][85][86][87][88] and sugars, [89][90][91][92] by the use of the R2PI, IR-R2PI, and UV-R2PI spectroscopies. The same techniques have been employed for investigating the structure and the conformational behavior of covalently bound diastereoisomers.…”