Multivalent presentation of mannose on hyperbranched polyglycerol and their interaction with concanavalin A lectin |
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Authors: | Papp Ilona Dernedde Jens Enders Sven Riese Sebastian B Shiao Tze Chieh Roy René Haag Rainer |
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Affiliation: | 1. Freie Universit?t Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195 Berlin (Germany), Fax: (+49)?30‐83853357;2. Charité‐Universit?tsmedizin Berlin, CBF, Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Hindenburgdamm 30, 12203 Berlin (Germany);3. Université du Québec à Montréal, Department of Chemistry, P.O. Box 8888, Succ. Centre‐Ville, Montréal (QC), H3C 3P8 (Canada) |
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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 Cu(I) -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 IC(50)) 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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Keywords: | click chemistry Con A lectin glycopolymers glycosylation multivalency |
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