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 (Concanavalin A). Surface plasmon resonance measurements showed these two families of mannosylated 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 1000 times more potent than mannose for their capacity to inhibit the binding of E. coli to erythrocytes in vitro.
Touaibia
Mohamed
M
Equipe PharmaQAM, Department of Chemistry, Université du Québec à Montréal, P.O. Box 8888 Succ centre-ville Montréal, Québec, H3C 3P8, Canada.
Wellens
Adinda
A
Shiao
Tze Chieh
TC
Wang
Qingan
Q
Sirois
Suzanne
S
Bouckaert
Julie
J
Roy
René
R
D018830:Adhesins, Escherichia coli / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry*; D036781:Fimbriae Proteins / Q000737:chemistry*; D008358:Mannose / Q000737:chemistry*; D036103:Nanotechnology
D018830:Adhesins, Escherichia coli; D050091:Dendrimers; C058769:fimH protein, E coli; D036781:Fimbriae Proteins; D008358:Mannose