Synthesis of Multivalent Carbohydrate-Centered Glycoclusters as Nanomolar Ligands of the Bacterial Lectin LecA from Pseudomonas aeruginosa

Authors

  • Dr. Marina L. Gening,

    1. Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow (Russia), Fax: (+7) 499-1358784
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  • Dr. Denis V. Titov,

    1. Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow (Russia), Fax: (+7) 499-1358784
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  • Dr. Samy Cecioni,

    1. Centre de Recherche sur les Macromolécules Végétales (CERMAV–CNRS UPR 5301), affiliated with Grenoble Université and ICMG, BP 53, 38041 Grenoble (France), Fax: (+33) 476-037-636
    2. Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique 2–Glycochimie, UMR 5246, CNRS, Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne (France), Fax: (+33) 472-448-109
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  • Dr. Aymeric Audfray,

    1. Centre de Recherche sur les Macromolécules Végétales (CERMAV–CNRS UPR 5301), affiliated with Grenoble Université and ICMG, BP 53, 38041 Grenoble (France), Fax: (+33) 476-037-636
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  • Dr. Alexey G. Gerbst,

    1. Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow (Russia), Fax: (+7) 499-1358784
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  • Dr. Yury E. Tsvetkov,

    1. Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow (Russia), Fax: (+7) 499-1358784
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  • Dr. Vadim B. Krylov,

    1. Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow (Russia), Fax: (+7) 499-1358784
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  • Dr. Anne Imberty,

    Corresponding author
    1. Centre de Recherche sur les Macromolécules Végétales (CERMAV–CNRS UPR 5301), affiliated with Grenoble Université and ICMG, BP 53, 38041 Grenoble (France), Fax: (+33) 476-037-636
    • Centre de Recherche sur les Macromolécules Végétales (CERMAV–CNRS UPR 5301), affiliated with Grenoble Université and ICMG, BP 53, 38041 Grenoble (France), Fax: (+33) 476-037-636
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  • Prof. Nikolay E. Nifantiev,

    Corresponding author
    1. Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow (Russia), Fax: (+7) 499-1358784
    • Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow (Russia), Fax: (+7) 499-1358784
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  • Dr. Sébastien Vidal

    Corresponding author
    1. Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique 2–Glycochimie, UMR 5246, CNRS, Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne (France), Fax: (+33) 472-448-109
    • Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique 2–Glycochimie, UMR 5246, CNRS, Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne (France), Fax: (+33) 472-448-109
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Abstract

A family of fifteen glycoclusters based on a cyclic oligo-(1→6)-β-D-glucosamine core has been designed as potential inhibitors of the bacterial lectin LecA with various valencies (from 2 to 4) and linkers. Evaluation of their binding properties towards LecA has been performed by a combination of hemagglutination inhibition assays (HIA), enzyme-linked lectin assays (ELLA), and isothermal titration microcalorimetry (ITC). Divalent ligands displayed dissociation constants in the sub-micromolar range and tetravalent ligands displayed low nanomolar affinities for this lectin. The influence of the linker could also be demonstrated; aromatic moieties are the best scaffolds for binding to the lectin. The affinities observed in vitro were then correlated with molecular models to rationalize the possible binding modes of these glycoclusters with the bacterial lectin.

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