LECTYN-GLYCAN ITERACTIONS .NEW NMR INSIGHTS ON THE ROLE DYNAMICS BY USING STATE OF THE ART NMR METHODOLOGIES

Sara Bertuzzi presents in her thesis a series of studies on several lectin/glycan interactions with relevant biological implications. State-of-the-art NMR and other analytical techniques (ITC, array screening) together with molecular modeling simulations, have been used to have a complete picture ofthe binding geometries and the dynamic aspects of lectin/glycan interactions. After a very complete and clear introduction on the structure and biological relevance of lectins and glycans, and after an insightful discussi on on the supramolecular basis of lectin /glycan interactions the following topics have been presented. A complete study on the molecular aspects ofthe interaction among Gal-1 lectin and blood group antigen fragments: the disaccharide LacNAc, a trisaccharide and two tetrasaccharides containing LacNAc as core. Interestingly, and in contrast with what has been found with another lectin, Gal-3, the tetrasaccharides bind to Gal-I with lower affinity than the LacNAc disaccharide.·A negative cooperativity has been found among the fucose units present in the tetrasaccharides and the LacNAc ligand. Dynamic studies through NMR also revealed that the binding of LacNAc induces important conformational dynamic changes in the structure of the lectin and this effect propagates to regions remote from ligand binding site.