Synthesis of a heparan sulfate mimetic disaccharide with a conformationally locked residue from a common intermediate

Carbohydr Res. 2009 Nov 23;344(17):2394-8. doi: 10.1016/j.carres.2009.09.012. Epub 2009 Sep 19.

Abstract

A simple mimetic of a heparan sulfate disaccharide sequence that binds to the growth factors FGF-1 and FGF-2 was synthesized by coupling a 2-azido-2-deoxy-D-glucopyranosyl trichloroacetimidate donor with a 1,6-anhydro-2-azido-2-deoxy-beta-D-glucopyranose acceptor. Both the donor and acceptor were obtained from a common intermediate readily obtained from D-glucal. Molecular docking calculations showed that the predicted locations of the disaccharide sulfo groups in the binding site of FGF-1 and FGF-2 are similar to the positions observed for co-crystallized heparin-derived oligosaccharides obtained from published crystal structures.

MeSH terms

  • Biomimetics*
  • Calcium Gluconate / chemistry
  • Computer Simulation
  • Disaccharides / chemical synthesis*
  • Fibroblast Growth Factor 1 / metabolism*
  • Fibroblast Growth Factor 2 / metabolism*
  • Heparitin Sulfate / chemical synthesis*
  • Heparitin Sulfate / metabolism
  • Molecular Conformation

Substances

  • Disaccharides
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 1
  • Heparitin Sulfate
  • Calcium Gluconate