A glycopolymer chaperone for fibroblast growth factor-2

Bioconjug Chem. 2004 Jan-Feb;15(1):145-51. doi: 10.1021/bc034138t.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acids
  • Animals
  • Cell Division / drug effects
  • Cells, Cultured
  • Chromatography, Thin Layer
  • Fibroblast Growth Factor 2 / chemistry*
  • Hot Temperature
  • Hydrolysis
  • Indicators and Reagents
  • Mice
  • Molecular Chaperones / chemical synthesis*
  • Molecular Chaperones / chemistry
  • Molecular Mimicry
  • Polymers / chemical synthesis*
  • Polymers / chemistry
  • Receptor Protein-Tyrosine Kinases / drug effects
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptors, Fibroblast Growth Factor / drug effects
  • Receptors, Fibroblast Growth Factor / metabolism
  • Solvents
  • Trypsin

Substances

  • Acids
  • Indicators and Reagents
  • Molecular Chaperones
  • Polymers
  • Receptors, Fibroblast Growth Factor
  • Solvents
  • Fibroblast Growth Factor 2
  • Fgfr1 protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • Trypsin