Interaction of trehalose and glucose with a peptide β-turn in aqueous solution

•Glucose forms strong H-bonds with the tripeptide GPG+, in competition with water.•Peptide β-turns are stretched and disrupted when glucose is added in solution.•Glucose and trehalose in peptide aqueous solutions have different co-solute behaviours. The issue of the interaction of carbohydrates with a peptide β-turn is tackled by investigating at the atomic scale the interaction of glucose and trehalose with an aqueous solution of Glycyl-L-prolyl-glycinamide·HCl. The study, performed by neutron diffraction with isotopic substitution augmented by Monte Carlo simulation analysis, evidences clear differences between the two systems. Indeed, while trehalose confines water within the hydration shell of the solute, glucose enters this shell, in competition with water molecules. As a result, the structure of β-turns in aqueous solution is stretched in presence of glucose as co-solute. This observations may be the key to distinguish the protection mechanism against drought from that against osmotic pressure.