Protein-carbohydrate recognition plays an important role in structural biology. Glycans store molecular information through their monosaccharide makeup, stereochemistry, linkage positions, branching, substitutions, and three-dimensional shapes. Glycans are often flexible and structurally diverse, and their interactions are typically individually weak. As a result, glycan recognition in biology usually cannot be described as a single, static ligand fitting into a protein binding pocket. Instead, it depends on a mix of factors, including glycan shape, protein structure, hydration, electrostatic forces, molecular movement, context, density, and multivalency. These factors have led structural glycobiology to shift from focusing only on isolated high-resolution structures to using both experimental and computational data to build models that span different spaces and times. This review examines the main ideas behind this shift. It highlights what makes carbohydrate recognition different from other ligand-protein interactions. It offers a practical, evidence-based way to interpret structural models.
So far unknown exocyclic 5-amino-1,2,3-triazole nucleosides were obtained by Dimroth rearrangement of 5-amino-1-ribosyl- and 5-methylamino-1-ribosyl-1H-1,2,3-triazole-4-carboxamides. The 5-NH2 starting compound was heated in DMF at 120 oC and the resulting mixture was next methylated under basic conditions providing four 5-ribosylamino products. For the substrate bearing 5-NHCH3 these conditions were insufficient for the rearrangement, but heating under reflux forced the formation of its 1-methyl-5-ribosylamino isomer. Interestingly, following Dimroth rearrangement an anomerization process occurred, leading to α- and β-anomers of exocyclic nucleosides. The α- and β-anomers of N3-methyl and β-anomer of N1-methyl products were isolated and identified based on multinuclear 1D and 2D NMR. The conformational preferences of their sugar moieties were also determined revealing significant differences between 1-ribosyl substrate and the corresponding rearrangement products. The progress of the Dimroth rearrangement was studied by variable-temperature NMR experiments.
