From glycodyn[n]arenes to dynamic polymers as multivalent ligand for lectins ; Des glycodyn[n]arènes aux polymères dynamiques comme ligands multivalents de lectines

Pseudomonas aeruginosa has developed increased resistance to antibiotics. Alternatives are being developed, including the study of anti-adhesive agents. This strategy aims to the inhibition of bacterial adhesion to host cells. In our laboratory, anti-adhesive glycoclusters have been designed and validated in vivo. The combination of multivalence and dynamic combinatorial chemistry could allow us to identify new glycoclusters of biological interest. Glycosylated dithiophenol building blocks were studied for the recognition of bacterial lectins. These dithiophenols had showed the preferential formation of glycodyn[3]arenes and glycodyn[4]arenes macrocycles. Biological studies are underway to evaluate their binding properties and toxicity in vitro. An additional generation of building blocks has been designed using a double dynamic combinatorial chemistry to allow the polymerisation of glycodyn[n]arenes into glycodynamers. A dithiophenol building block incorporating a polymerisable function (aldehyde/hydrazide) will be required to reach the glycodynamers, as well as water-soluble spacer arms for polymerisation. This will allow the transition from the lectin scale (glycodyn[n]arenes) to the bacterial scale (glycodynamers). Two dynamic orthogonal combinatorial chemistries will then be involved based on dithiophenol and aldehyde/hydrazide building blocks. ; La bactérie Pseudomonas aeruginosa a développé une résistance accrue aux antibiotiques. Des alternatives se développent, notamment l’étude d’agents antiadhésifs. Cette stratégie vise à bloquer les protéines à la surface de la bactérie pour empêcher son adhésion sur les cellules hôtes. Au sein du laboratoire, des glycoclusters antiadhésifs ont déjà été synthétisés et ont fait leurs preuves in vivo. L’alliance de la multivalence et de la chimie combinatoire dynamique pourrait nous permettre d’identifier de nouveaux glycoclusters d’intérêt biologique. Des briques moléculaires dithiophénol glycosylées ont été étudiées pour la reconnaissance de lectines bactériennes. ...