The impact of structural modification of sulfated polysaccharides on bone morphogenic protein 2 and inhibition of endothelial cell angiogenesis

Carbohydr Res. 2020 Oct:496:108093. doi: 10.1016/j.carres.2020.108093. Epub 2020 Jul 19.

Abstract

Sulfated polysaccharides play important roles in angiogenesis. However, the impact of structural alteration of sulfated polysaccharide on the bioactivity is still vague. In this study, binding between different sulfated polysaccharides and bone morphogenic protein 2 (BMP2) was measured to understand the sense of this motif transformation. The results showed that binding between sulfated α-1,4-glucan and BMP2 was the most intensive. The branch of α-1,4-glucan was important for the binding. The affinity of sulfated polysaccharides to BMP2 increased as the molecular weight (MW) and degree of substitution (DS) increased. DS that exceeded 1.05 impaired binding and played more important role in polysaccharide BMP2 interaction than MW. The reservation of partial 6-OH would benefit its binding ability to BMP2. Further, we showed that sulfated polysaccharides with strong binding to BMP2 blocked phosphorylation of Smad 1/5/8 and expression of Id1 to a greater extent than those not strongly bind to BMP2. The binding strength of polysaccharides to BMP2 increased, so did the potency of the anti-angiogenesis effects.

Keywords: Angiogenesis; Bone morphogenic protein 2; Structure and activity relationship; Sulfated polysaccharides.

MeSH terms

  • Bone Morphogenetic Protein 2 / metabolism*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Humans
  • Neovascularization, Physiologic / drug effects*
  • Polysaccharides / chemistry*
  • Polysaccharides / pharmacology*
  • Structure-Activity Relationship
  • Sulfates / chemistry*

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Polysaccharides
  • Sulfates