Folding Structures of Isolated Peptides as Revealed by Gas‐Phase Mid‐Infrared Spectroscopy

Abstract

To understand the intrinsic properties of peptides, which are determined by factors such as intramolecular hydrogen bonding, van der Waals bonding and electrostatic interactions, the conformational landscape of isolated protein building blocks in the gas phase was investigated. Here, we present IR-UV double-resonance spectra of jet-cooled, uncapped peptides containing a tryptophan (Trp) UV chromophore in the 1000-2000 cm(-1) spectral range. In the series Trp, Trp-Gly and Trp-Gly-Gly (where Gly stands for glycine), the number of detected conformers was found to decrease from six (Snoek et al., PCCP, 2001, 3, 1819) to four and two, respectively, which indicates a trend to relaxation to a global minimum. Density functional theory calculations reveal that the O-H in-plane bending vibration, together with the N-H in-plane bend ing and the peptide C=O stretching vibrations, is a sensitive probe to hydrogen bonding and, thus, to the folding of the peptide backbone in these structures. This enables the identification of spectroscopic fingerprints for the various conformational structures. By comparing the experimentally observed IR spectra with the calculated spectra, a unique conformational assignment can be made in most cases. The IR-UV spectrum of a Trp-containing nonapeptide (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu) was recorded as well and, although the IR spectrum is less well-resolved (and it probably results from different isomers), groups of amide I (peptide C=O stretching) and amide II (N-H in-plane bending) bands can still be recognised, in agreement with predictions at the AM1 level.

Potential‐Energy and Free‐Energy Surfaces of Glycyl‐Phenylalanyl‐Alanine (GFA) Tripeptide: Experiment and Theory

“…The existence of multiple g-turns in a peptide backbone has been addressed in the literature. [66,67] More interestingly and analogous to the case of Phe-Gly-Gly, [37] TrpGly [43,68,69] and Trp-Gly-Gly, [43,68,69] we observed none of the predicted CO 2 H bonded structures experimentally. This quite intriguing observation motivated us to review our calculations on the free-energy surface.…”

Conformational study of isolated pindolol by HF, DFT and MP2 calculations

“…2). This effect has already shown to play an important role in the stabilization of the folded conformers of various molecules with a structure similar to that of pindolol [11,12,14,26].…”

“…The starting structures were characterized by the possible formation of NHÁ Á Áp and OHÁ Á Áp interactions, which have been reported as relevant stabilization factors in the conformational space of other molecular systems similar to pindolol [11][12][13][14]. For this reason, it was found important to include these folded structures in the conformational analysis.…”

Phenyl-β-D-glucopyranoside and Phenyl-β-D-galactopyranoside Dimers: Small Structural Differences but Very Different Interactions

“…Note that the only difference between both monosacharides is the relative position of the O4H hydroxyl group. such as amino acids or peptides [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21], neurotransmitters [22][23][24][25][26][27][28], anesthetics [29,30], several mono-, di-and poly-saccharides [4,6,[31][32][33][34][35][36][37][38][39] or even micelles [40][41][42]. In these systems, the addition of a chromophore with an optically accessible excited electronic state is required to probe the molecules.…”