Vibrational CD studies of the solution conformation of simple alanyl peptides as a function of pH

Abstract

The CH-stretching vibrational CD (VCD) spectra of glycyl-L-alanine, L-alanylglycine, and L-alanyl-L-alanine have been studied at neutral, high, and low pH in D2O solution. The intense positive VCD band attributed to the C alpha H stretch of the alanyl residue in glycyl-L-alanine at neutral pH is absent in L-alanylglycine. In contrast to the VCD spectra of L-alanine, the positive methine-stretching VCD band in glycyl-L-alanine and L-alanyl-L-alanine is still present at pH 2. Based on the ring current mechanism, the VCD spectra are consistent with the presence of a five-membered CO...HN intramolecular hydrogen-bonded ring between the C-terminal carboxylate and peptide NH groups at neutral and high pH; and a seven-membered COH...O = C hydrogen-bonded ring between the C-terminal carboxyl OH and peptide C = O groups at low pH. In the N-terminal alanyl residue, the peptide C = O group is hydrogen bonded to the NH trans to the methine bond. The CH-stretching VCD spectra of L-alanyl-L-alanyl-L-alanine at neutral pH are consistent with two intramolecularly hydrogen-bonded conformations for the central alanyl residue.

Isotope-edited two-dimensional vibrational spectroscopy of trialanine in aqueous solution

“…21 Vibrational circular dichroism studies [22][23][24] have suggested that trialanine has a preferred conformation in aqueous solution, and our 2D results provided strong evidence confirming this. Since trialanine has only two peptide units, the only structure-related degrees of freedom are the two dihedral angles and ͑see Fig.…”

The Structure of Unfolded Peptides and Proteins Explored by Vibrational Spectroscopy

“…This paragraph focuses on their work on short peptides that do not form regular, canonical secondary structures. As an example, Figure 7.15 exhibits the IR and VCD spectrum of neutral, zwitterionic trialanine in D 2 O reported by Zuk et al (127) . In this context, they focused on the VCD signals of CH b and stretching modes.…”

l-Alanyl-l-alanine Conformational Changes Induced by pH As Monitored by the Raman Optical Activity Spectra

“…[4][5][6][7] Additionally, the inhomogeneous band broadening of the Raman and ROA spectral lines of small polar molecules could be recently interpreted in terms of molecular flexibilities. 8,9 As the previous NMR 10 and CD 11,12 studies indicate subtle changes in the L-alanyl-L-alanine (Ala-Ala) geometry upon pH change, in this work, we analyze the variances of the Raman and ROA spectra of the zwitterionic (AAZW), anionic (AA -), and cationic (AA + ) dipeptide ( Figure 1) to relate them to the conformational differences. The 15 N 13 C isotope analogue was synthesized and used for a more reliable assignment of the AAZW vibrational transitions of the backbone modes, whereas the more usual deuteration of the dialanine investigated before 13 enabled classification of the hydrogen stretching vibrations in particular.…”

“…Behavior of longer peptide molecules would be difficult to model with comparable accuracy. Previous spectroscopic studies of AA included, for example, infrared multiphoton dissociation spectroscopy, 14 CD, 11 NMR, vibrational circular dichroism (VCD), 13,15 and also Raman and ROA. 13,16 Computational studies 17,18 unambiguously confirm the importance to involve the aqueous environment in the modeling, as it stabilizes the conformation and charge states.…”