Synthetic heparan sulfate ligands for vascular endothelial growth factor to modulate angiogenesis

Chem Commun (Camb). 2021 Apr 11;57(28):3516-3519. doi: 10.1039/d1cc00964h. Epub 2021 Mar 11.

Abstract

We report the discovery of a potential heparan sulfate (HS) ligand to target several growth factors using 13 unique HS tetrasaccharide ligands. By employing an HS microarray and SPR, we deciphered the crucial structure-binding relationship of these glycans with the growth factors BMP2, VEGF165, HB-EGF, and FGF2. Notably, GlcNHAc(6-O-SO3-)-IdoA(2-O-SO3-) (HT-2,6S-NAc) tetrasaccharide showed strong binding with the VEGF165 growth factor. In vitro vascular endothelial cell proliferation, migration and angiogenesis was inhibited in the presence of VEGF165 and HT-2,6S-NAc or HT-6S-NAc, revealing the potential therapeutic role of these synthetic HS ligands.

MeSH terms

  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Heparitin Sulfate / chemical synthesis
  • Heparitin Sulfate / chemistry
  • Heparitin Sulfate / pharmacology*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Ligands
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Ligands
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Heparitin Sulfate