Molecular recognition by specific targets is at the heart of the life processes. In recent years, it has been shown that 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. The key tool for studying at atomic resolution the recognition processes in which glycans are involved is NMR. Thus, we use NMR as key tool for analysing key molecular recognition processes in which glycans are involved at atomic resolution.[1-8] Although the inherent flexibility of N-glycans and the chemical equivalence of individual branches precludes their NMR characterization using standard NMR methods, using multi-antennary N-glycans conjugated to a lanthanide binding tag, we have been able to discriminate the NMR signals of bi and multiantennary glycans with unprecedented resolution. As recent example, key details of biantennary glycan recognition by influenza hemagglutinin will be shown, with special emphasis in the application of novel paramagnetic-NMR methods to evaluate the relative importance of polar (hydrogen bonding, electrostatic interactions) and non-polar (van der Waals, CH-π) forces in the recognition process.
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