Characterizing Interactions Between Small Peptides and Dimethyl Sulfoxide Using Infrared Spectroscopy and Computational Methods

This study provides a comprehensive analysis of the interactions between dimethyl sulfoxide (DMSO) and two small peptides, diglycine and <i>N</i>-acetyl-glycine-methylamide (NAGMA), in aqueous solutions using FTIR spectroscopy and density functional theory (DFT) calculations. ATR-FTIR spectroscopy and DFT results revealed that DMSO does not form direct bonds with the peptides, suggesting that DMSO indirectly influences both peptides by modifying the surrounding water molecules. The analysis of HDO spectra allowed for the isolation of the contribution of water molecules that were simultaneously altered by the peptide and DMSO, and it also explained the changes in the hydration shells of the peptides in the presence of DMSO. In the DMSO-diglycine system, DMSO contributes to the additional strengthening of water hydrogen bonds in the reinforced hydration sphere of diglycine. In contrast, DMSO has a more moderate effect on the water molecules surrounding NAGMA due to the similarity of their hydration shells, leading to a slight weakening of the hydrogen bonds in the NAGMA hydration sphere. DFT/ONIOM calculations confirmed these observations. These findings demonstrated that DMSO influences peptide stability differentially based on their structural characteristics.