title: Multivalent presentation of mannose on hyperbranched polyglycerol and their interaction with concanavalin A lectin.
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.
authors.affiliation: Freie Universität Berlin, Institut für Chemie und Biochemie, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Papp
authors.forename: Jens
authors.initials: J
authors.lastname: Dernedde
authors.forename: Sven
authors.initials: S
authors.lastname: Enders
authors.forename: Sebastian B
authors.initials: SB
authors.lastname: Riese
authors.forename: Tze Chieh
authors.initials: TC
authors.lastname: Shiao
authors.forename: René
authors.initials: R
authors.lastname: Roy
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
mesh_terms: D003208:Concanavalin A / Q000737:chemistry* / Q000378:metabolism; D005990:Glycerol / Q000737:chemistry* / Q000378:metabolism; D008358:Mannose / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D011108:Polymers; D003208:Concanavalin A; C043941:polyglycerol; D005990:Glycerol; D008358:Mannose