Abstract:
« This thesis is part of a large research program related to the synthesis and controlled self-assembly of glycoamphiphiles for numerous applications such as biomedical, diagnostic, catalysis, cosmetic, etc. Here, we targeted glycoamphiphiles or glyco-hydrogelators which have the ability to hierarchically self-assemble in aqueous solution to form interpenetrating glyco-nanostructures and in-fine supramolecular hydrogels. Thus, two families of glycoamphiphiles were prepared according to a synthesis scheme including, for the b–C-glycosylbarbiturates family, the Knoevenagel condensation reaction with barbituric acid derivatives in water and, for the b–O-glycosylcarbamates family, the b-stereoselective carbamation reaction between sugars possessing the free anomeric hydroxyl function and fatty chain isocyanates. After a screening of carbohydrate derivatives varying the hydrophilic/hydrophobic balance (HLB), we found molecules allowing the gelation of aqueous solutions. Sodium salts of b–C-glycosylbarbiturates enabled the gelation of water in acidic medium and in the presence of calcium ions, to give different self-assembled glyco-nanostructures according to their shape parameters. Selective oxidative hydroxylation of the C-5 carbon of the barbiturate ring with hydrogen peroxide led to gelation of water at neutral pH. Moreover, we have shown the possibility of inducing gelation by the action of an a-glucosidase, thus giving perspectives in the treatment of pancreatic cancer. For b–O-glycosylcarbamates, we identified the right HLB ratio to form supramolecular hydrogels where glyco-nanostructures display maltose or melibiose on their surfaces. The melibiose-based hydrogel was considered as a mimic of the bacterial biofilm of Pseudomonas aeruginosa. We showed that the soluble lectin LecA produced by P. aeruginosa promoted gelation at low concentrations of the melibiose-based hydrogelator and to destabilize the hydrogel at higher concentrations. By transposition, these data provide valuable information on the role of the lectin concentration during the maturation of the bacterial biofilm. »
