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Clustering of Escherichia coli type-1 fimbrial adhesins by using multimeric heptyl α-D-mannoside probes with a carbohydrate core.
Almant, Mehdi; Moreau, Vincent; Kovensky, José; Bouckaert, Julie; Gouin, Sébastien G.
Afiliación
  • Almant M; Laboratoire des Glucides UMR CNRS 6219, Institut de Chimie de Picardie, UFR des Sciences, Université de Picardie Jules Verne, 33 rue Saint-Leu, 80039 Amiens Cedex 1, France.
Chemistry ; 17(36): 10029-38, 2011 Aug 29.
Article en En | MEDLINE | ID: mdl-21774001
ABSTRACT
Heptyl α-D-mannoside (HM) is a strong inhibitor of the FimH lectin that mediates the initial adhesion of the uropathogenic Escherichia coli (E. coli) to the bladder cells. We designed a set of multivalent HM ligands based on carbohydrate cores with structural valencies that range from 1 to 7. The chemical strategy used to construct the regular hydrophilic structures consisted of the repetition of a critical glucoside fragment. A primary amino group was grafted at the sugar reducing end to couple the multimers to a fluorescent label. A one-pot synthetic approach was developed to tether the ligands and the fluorescein isothiocyanate (FITC) probe to the scaffold simultaneously. Isothermal calorimetry with the monomeric FimH lectin revealed nanomolar affinities and saturation of all structurally available binding sites on the multivalent HM ligands. Direct titrations domain showed almost strict correlation of enthalpy-entropy compensation with increasing valency of the ligand, whereas reverse titration calorimetry demonstrated negative cooperativity between the first and the second binding site of the divalent heptyl mannoside. A multivalency effect was nevertheless observed by inhibiting the haemagglutination of type-1 piliated UTI89 E. coli, with a titer as low as 60 nM for the heptavalent HM ligand. An FITC-labeled HM trimer showed capture and cross-linking of living bacteria in solution, a phenomenon not previously described with low-valency ligands.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fluoresceína-5-Isotiocianato / Adhesinas de Escherichia coli / Proteínas Fimbrias / Escherichia coli / Colorantes Fluorescentes / Manósidos Idioma: En Revista: Chemistry Asunto de la revista: QUIMICA Año: 2011 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fluoresceína-5-Isotiocianato / Adhesinas de Escherichia coli / Proteínas Fimbrias / Escherichia coli / Colorantes Fluorescentes / Manósidos Idioma: En Revista: Chemistry Asunto de la revista: QUIMICA Año: 2011 Tipo del documento: Article País de afiliación: Francia