Mannosylated G(0) dendrimers with nanomolar affinities to Escherichia coli FimH

Pentaerythritol and bis-pentaerythritol scaffolds were used for the preparation of first generation glycodendrimers bearing aryl alpha-D-mannopyranoside residues assembled using single-step Sonogashira and click chemistry. The carbohydrate precursors were built with either para-iodophenyl, propargyl, or 2-azidoethyl aglycones whereas the pentaerythritol moieties were built with terminal azide or propargyl groups, respectively. Cross-linking abilities of this series of glycodendrimers were first evaluated with the lectin from Canavalia ensiformis (Concaavalin A). Surface plasmon resonance measurements showed these two families of monnosylated clusters as the best ligands known to date toward Escherichia coli K12 FimH with subnanomolar affinities. Tetramer 4 had a K-d of 0.45 nm. These clusters were 7000 times more potent than mannose for their capacity to inhibit the binding of E. coli to erythrocytes in vitro.