Abstract
The growth of multidrug resistance is one of the major public health issues of the 21st century. Pseudomonas aeruginosa (PA) ranks among the top five virulent bacterial pathogens. Many strategies have been developed to fight them and among them we investigated the use of glycoclusters to block PA virulence factors leading to the reduction of biofilm, adhesion and internalization. For this goal, we have particularly targeted the two soluble PA lectins: LecA and LecB that recognize specifically D-galactose and L-fucose respectively. Certain glycoclusters are able to decrease the biofilm formation of PAO1 strain and to reduce the internalization of PA in epithelial cells.On other hand, iron play an important role in growth and survival mechanisms in PA. In order to catch this mineral compound, microorganisms produce low molecular weight molecules named siderophores. Fe3+-siderophore complex is transported across membrane by sophisticated active transport. In goal to improve anti-infective activity of glycoclusters, it was imagined to combine glycoclusters with pseudo-siderophores. This «Trojan Horse» strategy could help glycoclusters to cross bacteria membrane and target the lectins that are located there. To this end, we have developed a synthesis strategy based on nucleic acid chemistry and click chemistry starting from simple building blocks. In this thesis, we will present the synthesis of these conjugates and their efficiency to target LecA and LecB.