Design, synthesis and biological evaluation of mannosyl triazoles as FimH antagonists

X-ray structures of FimH co-crystallized with two different ligands, the physiological binding epitope oligomannose-3 and a biphenyl α-d-mannoside revealed different binding modes, an in-docking-mode and an out-docking-mode, respectively. To accomplish the in-docking-mode, that is the docking mode where the ligand is hosted by the so-called tyrosine gate, FimH antagonists with increased flexibility were designed, synthesized and evaluated.