Supramolecular Glycosciences and Applications.
Pseudomonas aeruginosa is apathogen responsible for numerous diseases, mostly found in hospitals as acause for nosocomial infections. While the bacterium is rather inoffensive forhealthy people, immuno-compromised patients are much more exposed to suchinfections, which can be lethal. Moreover, it is quite difficult to cure aninfection involving Pseudomonasaeruginosa due to its high resistance to antibiotics. Anti-adhesivestrategies are inhibiting the adhesion of bacteria to host cells. Two solublemultivalent lectins (LecA and LecB) have been identified in this process.
Wehave studied the multivalent effect and designed several multivalentglycoclusters to inhibit these lectins with applications in vivo towards potential therapeutic anti-infectious agents. Nonetheless,whilea typical medicinal chemistry approach goes through the syntheses andinhibition assays of individual inhibitor candidates, dynamic combinatorialchemistry provides a rapid access to an equilibrating mixture of inhibitorcandidates through reversible covalent bonds under thermodynamic control. Wehave designed dynamic combinatorial libraries (DCLs) of glycoclustersself-assembling through disulfide bonds which composition can be modified uponan external stimulus such as lectins.
We have also demonstrated the influence of a modellectin (ConA) and its amplification of tri- and four-member ring macrocyles. Weperformed the same study with LecA and LecB toward potential therapeuticapplications.