Abstract
Mono- and disaccharide-containing glycopolymers were synthesized by cyanoxyl-mediated polymerization of acrylamide with acrylate-derivatized mono- and disaccharides. We demonstrate that a glycopolymer bearing pendant, fully sulfated lactose units effectively replaces heparin and heparan sulfate as a molecular chaperone for fibroblast growth factor-2 (FGF-2). Specifically, a compound was identified that protects FGF-2 from proteolytic, acid, and heat-induced degradation, while selectively promoting growth factor and receptor dimerization. Significantly, the capacity of this heparin-mimic to promote an FGF-2 specific proliferative cell response was confirmed and suggests potential applications for this compound and related derivatives in areas related to therapeutic angiogenesis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acids
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Animals
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Cell Division / drug effects
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Cells, Cultured
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Chromatography, Thin Layer
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Fibroblast Growth Factor 2 / chemistry*
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Hot Temperature
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Hydrolysis
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Indicators and Reagents
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Mice
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Molecular Chaperones / chemical synthesis*
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Molecular Chaperones / chemistry
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Molecular Mimicry
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Polymers / chemical synthesis*
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Polymers / chemistry
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Receptor Protein-Tyrosine Kinases / drug effects
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptor, Fibroblast Growth Factor, Type 1
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Receptors, Fibroblast Growth Factor / drug effects
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Receptors, Fibroblast Growth Factor / metabolism
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Solvents
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Trypsin
Substances
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Acids
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Indicators and Reagents
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Molecular Chaperones
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Polymers
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Receptors, Fibroblast Growth Factor
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Solvents
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Fibroblast Growth Factor 2
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Fgfr1 protein, mouse
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 1
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Trypsin