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

Abstract

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.

Effects of Sugar Functional Groups, Hydrophobicity, and Fluorination on Carbohydrate–DNA Stacking Interactions in Water

“…[11][12] Different monosaccharides were attached via an ethylene glycol spacer to the 5'-end of the selfcomplementary CGCGCG sequence using the corresponding protected carbohydrate phosphoramidite derivatives. Their synthesis was carried out by glycosylation of the spacer followed by standard phosphoramidite preparation (Scheme 1).…”

Magnitude of CH/O interactions between carbohydrate and water

“…The carbohydrate-aromatic interactions, which are sometimes denoted as CH/p interactions, were used for recognition of carbohydrates by artificial receptors [11][12][13][14]. The carbohydrate-aromatic interactions have been studied extensively both by experimental [15][16][17][18][19][20][21][22][23] and by theoretical [24][25][26][27][28][29][30][31][32][33][34][35] methods. The carbohydrate recognition processes involve desolvation of water molecules from the carbohydrate molecule.…”

Synthesis and in vitro inhibition properties of siRNA conjugates carrying glucose and galactose with different presentations

“…This approach has been previously used in our group to introduce several sugars in DNA [14,15]. We have extended this approach to prepare RNA-carbohydrate conjugates that possess one, two and four glucose or galactose moieties.…”

“…We have extended this approach to prepare RNA-carbohydrate conjugates that possess one, two and four glucose or galactose moieties. Glucose and galactose phosphoramidites carrying C2 and C3 spacers (scheme 2) were synthesized in two steps: classical glycosylation from their corresponding bromo peracetylated sugars and ethylene glycol or propylene glycol and subsequent standard phosphoramidite chemistry as described in [14,15].…”

“…The following sequences were prepared: Glucose- Galactose-C2 (10) is described in [14,15] whereas details for the preparation of according to the manufacturer's instructions.…”