Synthesis and hemagglutination inhibitory properties of mannose-tipped ligands: The effect of terminal phenyl groups and the linker between the mannose residue and the triazole moiety

Abstract

Two families (A, B) of triazole conjugates derived from d-mannose possessing reversed linkage functionality were easily assembled by Cu(I) catalyzed azide-alkyne cycloaddition reaction (CuAAC). The mannose precursors were built with either 3-azidopropyl or propargyl aglycones whereas the phenyl moieties were built with terminal azide or propargyl groups, respectively. In a hemagglutination inhibition (HAI) assay, family A (7a-11a), where the linker between the mannose residue and the triazole ring is three carbons displayed a 3-5 fold enhancement in activity compared to family B (13a-17a) having methyl-triazolyl moiety. The representative ligand 7a, where the terminal phenyl ring is substituted with an ester group and Cl atom exhibited the highest inhibitory activity with an HAI titer of 8 μM. This compound could be a good candidate for the further design of potent mannosyl ligands targeting FimH fimbrial lectin.

Keywords: Click chemistry; FimH; Hemagglutination; Mannoconjugate; Urinary tract infection.