Conformation dependence of the C^αD^α stretch mode in peptides: Side‐chain influence in dipeptide structures

Abstract

We have shown by theoretical studies of alanine peptides that the C(α)D(α) stretch frequency could be particularly useful for determining peptide structure because of its sensitivity to the ϕ,ψ torsion angles at the C(α) atom. To demonstrate that this is a robust methodology worthy of experimental exploration, we have also shown that this mode is even more determinative of conformation in aqueous solution, mainly as a result of the development of differential C(α)--D(α)···O(water) interactions. As further assurance, we now determine the influence of the side chain on this band, showing for aliphatic, a polar, and an aromatic side chains that the dependence is minor and explaining why this is also expected for other side chains. These results should stimulate new experimental methodologies in the field of peptide structure determination.

Water interaction differences determine the relative energetic stability of the polyproline II conformation of the alanine dipeptide in aqueous environments

“…These insights make it clear that such a relative stability is likely to be sensi-tive to such factors as the length and the sequence of peptide conformations, as well as on the nature of the side chains. 50,91 We are currently investigating the influences of these factors on the energetics. The generally observed temperature dependence of the circular dichroism spectra of peptide systems indicates that the entropic component of the free energy difference will favor the b-conformation as the temperature increases.…”

“…Analysis of the relative intensity of the two characteristic bands in the CD spectrum, which according to theory is a function of the number of adjacent PPII conformations, 19 may help in clarifying this issue. We have proposed a new technique that could provide this information through an analysis of the C a D a stretch mode at individually isotopically substituted sites, [47][48][49][50] this frequency being found to depend mainly on the u,w torsion angles at the site. We hope that this methodology can be implemented in studies of such systems.…”

Probe of Alcohol Structures in the Gas and Liquid States Using C–H Stretching Raman Spectroscopy

“…Therefore, these five bands only correspond to the five conformers of 1-propanol. In previous studies, the results from theoretical predictions have shown that the C–H stretching vibrations can be used to characterize the backbone conformations of protein and peptides [ 9 , 10 , 11 , 12 ]. However, the experimental evidence is limited.…”

“…Therefore, one of the important aspects of applying vibrational spectroscopy is to develop the appropriate vibrational probes that can characterize molecular specific information such as the conformation and intermolecular interaction. Many chemical groups have been established as vibrational probes in the literature, including the thiocyanate group (–SCN), azide group (–N 3 ), diazo group (–N 2 ), the alkyne (–C≡C–), amide group (–CONH 2 ), amine group (–NH 2 ), carbonyl group (–C=O), hydroxyl group (–OH), –SH group, –CH group, and so on, as summarized in recent several reviews [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. For example, using the site-specific nitrile group (–C≡N) as a probe of protein structure, it was shown that –CN frequencies could discriminate between the solvent-exposed residues and residues buried in the hydrophobic core of a protein [ 23 ].…”

“…(i) The –CH chemical groups exist widely in organic and biological molecules, which render it possible to become a general tool in molecules; (ii) C–H stretching vibrations not only have relatively high intensity in both infrared and Raman spectra but are also separated from coupling with other vibrational modes; (iii) The C–H probe is sensitive to the local molecular environment. For example, recent theoretical studies have shown that the site-specific C–H stretching vibrations are very sensitive to the backbone conformation of peptide and protein structures [ 9 , 10 , 11 , 12 ]; (iv) The C–H probe does not perturb the molecular systems being investigated, which is different from extrinsic molecular probes incorporated into molecules such as the azide group (–N 3 ) [ 20 ]. As a result of these features, the spectra in the C–H stretching region of 2800–3100 cm −1 were widely employed to investigate the molecular structure, intermolecular interactions, gas/liquid interface effect, vibrational energy redistribution mechanism, biological imaging, and identification of polycyclic aromatic hydrocarbons in astrophysics [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ].…”