916849-20-2Relevant articles and documents
Evaluation of the carbohydrate recognition domain of the bacterial adhesin FimH: Design, synthesis and binding properties of mannoside ligands
Sperling, Oliver,Fuchs, Andreas,Lindhorst, Thisbe K.
, p. 3913 - 3922 (2006)
Fimbriae are proteinogeneous appendages on the surface of bacteria, which mediate bacterial adhesion to the host cell glycocalyx. The so-called type 1 fimbriae exhibit specificity for α-d-mannosides and, therefore, they are assumed to mediate bacterial adhesion via the interaction of a fimbrial lectin and α-d-mannosyl residues exposed on the host cell surface. This carbohydrate-specific adhesive protein subunit of type 1 fimbriae has been identified as a protein called FimH. The crystal structure of this lectin is known and, based on this information, the molecular details of the interaction of mannoside ligands and FimH are addressed in this paper. Computer-based docking methods were used to evaluate known ligands as well as to design new ones. Then, a series of new mannosides with extended aglycon was synthesized and tested as inhibitors of type 1 fimbriae-mediated bacterial adhesion in an ELISA. The results obtained were compared to the predictions and findings as delivered by molecular modeling. This study led to an improved understanding of the ligand-receptor interactions under investigation. The Royal Society of Chemistry 2006.
