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The First Simplified Heparan Sulphate-Alginate Hybrid Trisaccharides: Synthesis and Biological Effects on Human
Katalin Kútvölgyi1,2,3, Zsófia Peleskei1,2, Fruzsina Demeter1
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
International Journal of Molecular Sciences
|September 13, 2025
Summary
Researchers synthesized novel heparan sulfate analogues containing d-mannuronic acid. Some trisaccharide derivatives demonstrated anti-inflammatory effects by suppressing interleukin-6 release in human dermal fibroblasts.
Area of Science:
- Biochemistry
- Carbohydrate Chemistry
- Immunology
Background:
- Glycosaminoglycans (GAGs) are vital heteropolysaccharides with uronic acid building blocks.
- Alginates, composed of d-mannuronic and α-l-guluronic acids, possess biological activities.
- d-mannuronic acid analogues in GAGs were previously unknown.
Purpose of the Study:
- To synthesize novel heparan sulfate analogue trisaccharides incorporating d-mannuronic acid.
- To investigate the biological effects of these synthesized trisaccharides on human dermal fibroblasts.
- To explore potential anti-inflammatory properties and effects on collagen production.
Main Methods:
- Chemical synthesis of heparan sulfate analogue trisaccharides with d-mannuronic acid.
- Culturing primary human dermal fibroblasts.
- Assessing cell viability, spontaneous collagen production, and poly(I:C)-induced interleukin-6 release.
Main Results:
- None of the synthesized trisaccharides affected fibroblast viability or spontaneous collagen production at 10 μM.
- Certain d-mannuronic acid-containing trisaccharide derivatives exhibited anti-inflammatory activity.
- These active derivatives suppressed the release of interleukin-6 induced by poly(I:C).
Conclusions:
- Novel d-mannuronic acid-containing trisaccharides were successfully synthesized.
- These compounds show potential as anti-inflammatory agents, specifically by modulating interleukin-6 release.
- Further research into alginate and GAGs analogues could yield new therapeutic strategies.
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