Lanthanide-Chelating Carbohydrate Conjugates Are Useful Tools To Characterize Carbohydrate Conformation in Solution and Sensitive Sensors to Detect Carbohydrate–Protein Interactions

The increasing interest in the functional versatility of glycan epitopes in cellular glycoconjugates calls for developing sensitive methods to define carbohydrate conformation in solution and to characterize protein–carbohydrate interactions. Measurements of pseudocontact shifts in the presence of a paramagnetic cation can provide such information. In this work, the energetically privileged conformation of a disaccharide (lactose as test case) was experimentally inferred by using a synthetic carbohydrate conjugate bearing a lanthanide binding tag. In addition, the binding of lactose to a biomedically relevant receptor (the human adhesion/growth-regulatory lectin galectin-3) and its consequences in structural terms were defined, using Dy3+, Tb3+, and Tm3+. The described approach, complementing the previously tested protein tagging as a way to exploit paramagnetism, enables to detect binding, even weak interactions, and to characterize in detail topological aspects useful for physiological ligands and mimetics in drug design.