The synthesis and biological evaluation of chondroitin sulfate E glycodendrimers

Future Med Chem. 2019 Jun;11(12):1403-1415. doi: 10.4155/fmc-2019-0011. Epub 2019 Jul 15.

Abstract

Aim: Chondroitin sulfate (CS) is a class of highly sulfated polysaccharides that possess many important biological functions. The heterogeneity of CS limits pharmacological research and leads to ambiguous mechanisms. Thus, glycomimetics are demanded as replacement of natural polysaccharides to explore important biological processes. Results & methodology: Here the preparation of CS glycodendrimers is reported as well as their use as CS mimetics to regulate the NF-κB pathway. Multivalent presentation of sugar epitopes on appropriate dendrimer scaffolds increased the suppression of the NF-κB pathway. The interaction between CS-E molecules and TNF-α was examined by nuclear magnetic resonance technology. Conclusion: Overall, the glycodendrimer reported here may be potentially employed as molecular tool to investigate the biological functions of CS.

Keywords: NF-κB; chondroitin sulfate E; dendrimers; glycomimetics; multivalent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chondroitin Sulfates / chemical synthesis*
  • Chondroitin Sulfates / chemistry
  • Chondroitin Sulfates / pharmacology
  • Dendrimers / chemical synthesis*
  • Dendrimers / chemistry
  • Dendrimers / pharmacology
  • Gene Expression / drug effects
  • Genes, Reporter
  • Glycosides / chemical synthesis*
  • Glycosides / chemistry
  • Glycosides / pharmacology
  • Mice
  • Molecular Structure
  • NF-kappa B / genetics
  • RAW 264.7 Cells
  • Transcriptional Activation / drug effects
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Dendrimers
  • Glycosides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Chondroitin Sulfates