Comparative Study of Aryl <i>O</i>-, <i>C</i>-, and <i>S</i>-Mannopyranosides as Potential Adhesion Inhibitors toward Uropathogenic <i>E. coli</i> FimH

Abstract

A set of three mannopyranoside possessing identical 1,1′-biphenyl glycosidic pharmacophore but different aglyconic atoms were synthesized using either a palladium-catalyzed Heck cross coupling reaction or a metathesis reaction between their corresponding allylic glycoside derivatives. Their X-ray structures, together with their calculated 3D structures, showed strong indicators to explain the observed relative binding abilities against E. coli FimH as measured by a improved surface plasmon resonance (SPR) method. Amongst the O-, C-, and S-linked analogs, the C-linked analog showed the best ability to become a lead candidate as antagonist against uropathogenic E. coli with a Kd of 11.45 nM.

Keywords

• carbohydrate
• d-mannosides
• uropathogenic infections
• <i>e. coli</i>
• lectin
• fimh
• heck reaction
• metathesis
• spr
• x-ray