Synthesis of hyaluronic acid oligosaccharides with a GlcNAc-GlcA repeating pattern and their binding affinity with CD44

Che-Jui Yeh, Medel Manuel L. Zulueta, Yaw-Kuen Li, Shang-Cheng Hung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Hyaluronic acid (HA) is a ubiquitous glycosaminoglycan in the extracellular matrix and a ligand of CD44, a transmembrane glycoprotein that is important in cell migration. Crystal and NMR studies found a hexasaccharide of the pattern (GlcA-GlcNAc)(3)as the shortest HA that could bind to CD44, but molecular dynamics simulations indicated that a tetrasaccharide of the pattern (GlcNAc-GlcA)(2)is the key structure interacting with CD44. Access to oligomers with such a repeat pattern is crucial in binding studies with CD44. Here we developed a synthetic procedure to afford the HA oligosaccharides with the GlcNAc-GlcA repeating unit and measured the binding interaction between these sugars and human CD44 by isothermal titration calorimetry (ITC). During the chemical synthesis, we successfully generated the beta-glycosidic bond in the absence of neighbouring group participation and overcome the issues in the oxidation step. In addition, ammonia-free dissolving metal reduction for debenzylation and azido reduction has been applied in carbohydrate synthesis for the first time. ITC analysis revealed that the HA tetrasaccharide (GlcNAc-GlcA)(2)could indeed interact and bind to the human CD44.

Original languageEnglish
Pages (from-to)5370-5387
Number of pages18
JournalOrganic and Biomolecular Chemistry
Volume18
Issue number28
DOIs
StatePublished - 28 Jul 2020

Keywords

  • SOLID-PHASE SYNTHESIS
  • GLUCURONIC-ACID
  • DOMAIN
  • SITE
  • PARTICIPATION
  • DISACCHARIDES
  • SACCHARIDES
  • FRAGMENT
  • COMPLEX
  • TETRA

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