Sulfonated Copolymers as Heparin-Mimicking Stabilizer of Fibroblast Growth Factor: Size, Architecture, and Monomer Distribution Effects

Fibroblast growth factors (FGF) are involved in a wide range of biological processes such as cell proliferation and differentiation. In living organisms, the binding of FGF to its receptors are mediated through electrostatic interactions between FGF and naturally occurring heparin. Despite its preva...

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Veröffentlicht in:Biomacromolecules 2019-01, Vol.20 (1), p.285-293
Hauptverfasser: Bray, Caroline, Gurnani, Pratik, Mansfield, Edward D. H, Peltier, Raoul, Perrier, Sébastien
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Sprache:eng
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Zusammenfassung:Fibroblast growth factors (FGF) are involved in a wide range of biological processes such as cell proliferation and differentiation. In living organisms, the binding of FGF to its receptors are mediated through electrostatic interactions between FGF and naturally occurring heparin. Despite its prevalent use in medicine, heparin carries notable limitations; namely, its extraction from natural sources (expensive, low yield and extensive purification), viral contamination, and batch-to-batch heterogeneity. In this work a range of synthetic homopolymers and copolymers of sodium 2-acrylamido-2-methylpropanesulfonate were evaluated as potential FGF stabilizers. This was studied by measuring the proliferation of BaF3-FR1c cells, as a model assay, and the results will be compared with the natural stabilization and activation of FGF by heparin. This study explores the structure–activity relationship of these polysulfonated polymers with a focus on the effect of molecular weight, comonomer type, charge dispersion, and polymer architecture on protein stabilization.
ISSN:1525-7797
1526-4602
DOI:10.1021/acs.biomac.8b01451