Conformational preferences of alanine tripeptide in water, trifluoroethanol and dimethyl sulfoxide studied by vibrational spectroscopy

Alanine tripeptide is a good model molecule to analyze a conformational distribution of an unstructured peptide backbone, to study a competition between the intraand intermolecular hydrogen-bonding, as well as the favourable solvation conditions. In our work, we used three different spectroscopic techniques, the Raman and infrared (IR) spectroscopy, and the vibrational circular dichroism (VCD) that are conformation-sensitive and provide information about hydrogen bonded carbonyl groups (amide I region) and amino groups (amide II and III regions in the spectrum) of a peptide backbone. Alanine tripeptide in water exhibits low-frequency bands in the amide I region at 1618 cm-1 and in the amide III region at 1260 cm-1, suggesting a strong intramolecular hydrogen bond indicative of a C7 conformation. This bond is disrupted in dimethyl sulfoxide (DMSO) where the solvent molecules interact with amino groups of alanine tripeptide forming intermolecular hydrogen bonds. A similar situation is found in trifluoroethanol (TFE) where alanine tripeptide forms mainly intermolecular hydrogen bonds with a hydrogen donor from solvent molecules.