Thesis defense: Aicha ABDALLAH

This work investigates the development of novel Glycoamphiphiles (GAs) integrated into a Liquid Crystal (LC)-based biosensor to detect nosocomial infections and plant pathogens through carbohydrate-lectin interactions. Healthcare-associated infections, caused by pathogenic microorganisms, pose a significant challenge to patient safety. These pathogens use lectins, proteins that specifically recognize carbohydrate structures on host cells, to initiate infection. GAs were explored as potential anti-adhesive self-assembled agents and diagnostic tools for pathogen detection, focusing on opportunistic bacteria such as Pseudomonas aeruginosa and plant pathogens like Ralstonia solanacearum. The research aimed to address a simple and low-cost diagnostic method by leveraging the selectivity and sensitivity of LC-based biosensors, which offer a rapid, simple, and efficient approach to biomolecular detection with amplified output signals observable by the naked eye. A key aspect of this work was the development of a streamlined synthetic approach to GAs, utilizing non-reductive amination of protecting group-free carbohydrates with readily accessible ortho-substituted aniline derivatives from isatoic anhydride. Microwave-assisted b-N-arylation of unprotected carbohydrates was efficient in terms of improved yields and shortened reaction time. The resulting GAs self-assembled into intriguing glyconanostructures of various morphologies in solution, which we attempted to rationalize with packing parameters. A positional isomeric and solvent effect on morphological transitions was observed, featuring dynamic supramolecular structures. Biophysical characterization of these GAs revealed their binding affinities to lectins from pathogenic bacteria. Finally, the thesis validated the proof-of-concept by building an LC-based biosensor with GAs adsorbed at the surface of LCs, allowing optical detection of pathogenic lectins through specific carbohydrate-lectin interactions.