Synthesis of hyaluronic acid oligosaccharides with a GlcNAc–GlcA repeating pattern and their binding affinity with CD44
| Autor: | Shang-Cheng Hung, Che-Jui Yeh, Medel Manuel L. Zulueta, Yaw-Kuen Li |
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| Rok vydání: | 2020 |
| Předmět: |
Binding Sites
Stereochemistry Organic Chemistry Carbohydrate synthesis Oligosaccharides Isothermal titration calorimetry Ligand (biochemistry) Biochemistry Chemical synthesis chemistry.chemical_compound Hyaluronan Receptors Solid-phase synthesis chemistry Hyaluronic acid Carbohydrate Conformation Neighbouring group participation Humans Tetrasaccharide Hyaluronic Acid Physical and Theoretical Chemistry Oxidation-Reduction |
| Zdroj: | Organic & Biomolecular Chemistry. 18:5370-5387 |
| ISSN: | 1477-0539 1477-0520 |
| Popis: | 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 β-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. |
| Databáze: | OpenAIRE |
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