title: A focused sulfated glycoconjugate Ugi library for probing heparan sulfate-binding angiogenic growth factors.
abstract: A library of small molecule heparan sulfate (HS) mimetics was synthesized by employing the Ugi four-component condensation of d-mannopyranoside-derived isocyanides with formaldehyde as the carbonyl component and a selection of carboxylic acids and amines, followed by sulfonation. The library was used to probe the subtle differences surrounding the ionic binding sites of three HS-binding angiogenic growth factors (FGF-1, FGF-2 and VEGF). Each compound features 3 or 4 sulfo groups which serve to anchor the ligand to the HS-binding site of the protein, with a diverse array of functionality in place extending from C-1 or C-6 to probe for adjacent favorable binding interactions. Selectivity of binding to these proteins was clearly observed and supported by molecular docking calculations.
authors.affiliation: Progen Pharmaceuticals Limited, Brisbane, Qld 4076, Australia; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld 4072, Australia. l.liu@imb.uq.edu.au
authors.forename: Ligong
authors.initials: L
authors.lastname: Liu
authors.forename: Caiping
authors.initials: C
authors.lastname: Li
authors.forename: Siska
authors.initials: S
authors.lastname: Cochran
authors.forename: Daniel
authors.initials: D
authors.lastname: Feder
authors.forename: Luke W
authors.initials: LW
authors.lastname: Guddat
authors.forename: Vito
authors.initials: V
authors.lastname: Ferro
mesh_terms: D001665:Binding Sites; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry*; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry*; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry*; D013431:Sulfates / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry*
chemical_list: D006001:Glycoconjugates; D008024:Ligands; D054852:Small Molecule Libraries; D013431:Sulfates; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1