Synthetic glycolipids as modulators of carbohydrate-protein interactions

Zusammenfassung

hapter 1 contains a general introduction that describes the importance of glycobiology and the role of multivalent systems in the study of carbohydrate-protein interactions. Chapter 2 sets out the general objectives of this thesis. The research in Chapter 3 describes the synthesis of a series of glycolipids that presents modifications either in the pyranose ring or in the aglycone moiety and their evaluation as potent inhibitors, together with multivalent systems that presents glycolipids, against glycosidases. It was found that modifications in the aglycone moiety and in the pyranose ring played important role in potency. Moreover, glycocluster that presents 4 glycolipids monomers gave the best inhibitor potency per sugar. The research in Chapter 4 describes the synthesis of multivalent structures with two different central cores (hyperbranched polymers and dendrimers) that allow the presentation of carbohydrate residues in a polydispers or monodispers manner. Binding was detected using DLS and SPR techniques. Strong interactions in a non-saturated protein concentration, revealed by aggregates formation and binding, were found for polydispers multivalent systems. The research in Chapter 5 explores a novel strategy for the design of multivalent inhibitors based on glycodendriprotein-based nanocapsules. In order to explore how the different glycodendrimer architecture affects the binding properties, BLI experiments were carried out to determine the IC50 of the tested glycodendrimers. The site selective protein modification was also studied for a further glycodendriprotein-based nanocapsules formation. The research in Chapter 6 explores the synthesis of fluorosugar reagents for the construction of well-defined fluoroglycoproteins. A general strategy to access a wide range of fluorosugars, via a glycosyl iodide intermediate, that are useful reagents for chemical-site selective protein glycosylation were disclosed. Chapter 7 presents the final remarks and conclusions extracted from the results obtained in this thesis.