A holistic approach to unravelling chondroitin sulfation: Correlations between surface charge, structure and binding to growth factors

Carbohydr Polym. 2018 Dec 15:202:211-218. doi: 10.1016/j.carbpol.2018.08.120. Epub 2018 Aug 30.

Abstract

Chondroitin sulfate (CS) is a relevant family of polysaccharides that participates in a large variety of biological events that are related to neural processes by regulating various growth factors through the pattern and degree of sulfation of the polysaccharide. However, their own complexity makes their optimization for biomedical applications a difficult undertaking. Thus, a different perspective has to be taken. Herein, we show that the particular sulfate distribution within the disaccharide repeating-unit plays a key role in the binding of growth factors (GFs). In particular, this disposition modulates the surface charge of the helical structure that, interestingly, has a significant influence on the binding capacity of CSs with several GFs. This fact should be carefully considered in the design of new ligands with improved activity as GFs ligands.

Keywords: Chondroitin sulfate; Glycosaminoglycan; Protein interactions; Structure-activity relationships.

MeSH terms

  • Animals
  • Binding Sites
  • Carbohydrate Conformation
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chondroitin Lyases / metabolism
  • Chondroitin Sulfates / chemical synthesis
  • Chondroitin Sulfates / chemistry*
  • Chondroitin Sulfates / pharmacology
  • Fibroblast Growth Factors / chemistry*
  • Humans
  • Ligands
  • Particle Size
  • Rats
  • Spectrometry, Fluorescence
  • Surface Properties

Substances

  • Ligands
  • Fibroblast Growth Factors
  • Chondroitin Sulfates
  • Chondroitin Lyases