Molecular recognition by specific targets is at the heart of the life processes. The interactions between proteins (lectins, enzymes, antibodies) and carbohydrates mediate a broad range of biological activities, from fertilization and tissue maturation to pathological processes. The elucidation of the mechanisms that govern how sugars are accommodated in the binding sites of these receptors is currently a topic of interest. Thus, unravelling the structural and conformational factors and the physicochemical features that rule the interactions of these molecules is of paramount interest.
Solution NMR is unique in providing stereochemical and conformational information. Given the inherent flexibility and dynamic properties of glycans, we use NMR as key tool for deducing at atomic resolution molecular recognition processes in which glycans are involved, also assisted by a variety of synthetic, molecular biology, computational and biophysical techniques.
This presentation is focused on the application of state-of-the-art NMR methods both from the ligand and receptor’s perspective to study molecular recognition processes between receptors of biomedical interest and glycans. As recent examples, key details of glycan recognition by these receptors will be shown, with special emphasis in the interactions of the human blood antigens with galectins, of sialoglycans with Siglecs, and of the the spike glycoprotein of SARS CoV-2 with human immune lectins and cell glycans.