Experimental Measurement of Carbohydrate–Aromatic Stacking in Water by Using a Dangling-Ended DNA Model System

Protein–carbohydrate recognition is of fundamental importance for a large number of biological processes; carbohydrate–aromatic stacking is a widespread, but poorly understood, structural motif in this recognition. We describe, for the first time, the measurement of carbohydrate–aromatic interactions from their contribution to the stability of a dangling-ended DNA model system. We observe clear differences in the energetics of the interactions of several monosaccharides with a benzene moiety depending on the number of hydroxy groups, the stereochemistry, and the presence of a methyl group in the pyranose ring. A fucose–benzene pair is the most stabilizing of the studied series (-0.4 Kcal mol-1) and this interaction can be placed in the same range as other more studied interactions with aromatic residues of proteins, such as Phe–Phe, Phe–Met, or Phe–His. The noncovalent forces involved seem to be dispersion forces and nonconventional hydrogen bonds, whereas hydrophobic effects do not seem to drive the interaction.