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Multivalent Presentation of Mannose on Hyperbranched Polyglycerol and their Interaction with Concanavalin A Lectin

Authors

  • Ilona Papp,

    1. Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195 Berlin (Germany), Fax: (+49) 30-83853357
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  • Dr. Jens Dernedde,

    1. Charité-Universitätsmedizin Berlin, CBF, Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Hindenburgdamm 30, 12203 Berlin (Germany)
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  • Dr. Sven Enders,

    1. Charité-Universitätsmedizin Berlin, CBF, Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Hindenburgdamm 30, 12203 Berlin (Germany)
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  • Sebastian B. Riese,

    1. Charité-Universitätsmedizin Berlin, CBF, Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Hindenburgdamm 30, 12203 Berlin (Germany)
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  • Tze Chieh Shiao,

    1. Université du Québec à Montréal, Department of Chemistry, P.O. Box 8888, Succ. Centre-Ville, Montréal (QC), H3C 3P8 (Canada)
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  • Prof. René Roy,

    1. Université du Québec à Montréal, Department of Chemistry, P.O. Box 8888, Succ. Centre-Ville, Montréal (QC), H3C 3P8 (Canada)
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  • Prof. Rainer Haag

    Corresponding author
    1. Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195 Berlin (Germany), Fax: (+49) 30-83853357
    • Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195 Berlin (Germany), Fax: (+49) 30-83853357
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Abstract

We describe the synthesis of multivalent mannose derivatives by using hyperbranched polyglycerols (hPG) as a scaffold with different linker structures. Grafting of protected mannose (Man) units is achieved by using CuI-catalyzed Huisgen click chemistry with either an anomeric azide or propargyl ether onto complementarily functionalized alkyne or azido polymer surfaces. NMR spectroscopy, dynamic light scattering (DLS), IR spectroscopy, size-exclusion chromatography (SEC), and elemental analysis have been used to characterize the hPG–Man compounds. The surface availability and bioactivity of Man-modified polymers were evaluated by using a competitive surface plasmon resonance (SPR)-based binding assay by interactions of the glycopolymers with concanavalin A (Con A), a lectin that binds mannose containing molecules. The results indicated that the novel glycoarchitectures presented in this work are efficient inhibitors of Con A–mannose recognition and resulted in inhibitor concentrations (mean IC50) from the micro- to the nanomolar range, whereas the corresponding monovalent mannoside (methyl-Man) requires millimolar concentrations. The results provide an interesting structure–activity relationship for libraries of materials that differ in the linkage of the sugar moiety presented on a biocompatible polyglycerol scaffold.

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