Hyaluronan (HA)-inspired glycopolymers as molecular tools for studying HA functions
| Autor: | Alessandra Monaco, Gokhan Yilmaz, Guy Ochbaum, Helena S. Azevedo, Dominic W. P. Collis, Richard M. Napier, Veselina Uzunova, Yichen Yuan, C. Remzi Becer, Yejiao Shi, Ronit Bitton, Clare O'Malley |
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| Rok vydání: | 2021 |
| Předmět: |
Glycan
02 engineering and technology 010402 general chemistry 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) Biochemistry Glycosaminoglycan chemistry.chemical_compound Glucosamine Hyaluronic acid Monosaccharide Surface plasmon resonance Molecular Biology chemistry.chemical_classification biology Chemical glycosylation 021001 nanoscience & nanotechnology Glucuronic acid QP 3. Good health 0104 chemical sciences Chemistry chemistry Chemistry (miscellaneous) biology.protein 0210 nano-technology |
| Zdroj: | RSC Chemical Biology |
| ISSN: | 2633-0679 |
| DOI: | 10.1039/d0cb00223b |
| Popis: | Hyaluronic acid (HA), the only non-sulphated glycosaminoglycan, serves numerous structural and biological functions in the human body, from providing viscoelasticity in tissues to creating hydrated environments for cell migration and proliferation. HA is also involved in the regulation of morphogenesis, inflammation and tumorigenesis through interactions with specific HA-binding proteins. Whilst the physicochemical and biological properties of HA have been widely studied for decades, the exact mechanisms by which HA exerts its multiple functions are not completely understood. Glycopolymers offer a simple and precise synthetic platform for the preparation of glycan analogues, being an alternative to the demanding synthetic chemical glycosylation. A library of homo, statistical and alternating HA glycopolymers were synthesised by reversible addition–fragmentation chain transfer polymerisation and post-modification utilising copper alkyne–azide cycloaddition to graft orthogonal pendant HA monosaccharides (N-acetyl glucosamine: GlcNAc and glucuronic acid: GlcA) onto the polymer. Using surface plasmon resonance, the binding of the glycopolymers to known HA-binding peptides and proteins (CD44, hyaluronidase) was assessed and compared to carbohydrate-binding proteins (lectins). These studies revealed potential structure-binding relationships between HA monosaccharides and HA receptors and novel HA binders, such as Dectin-1 and DEC-205 lectins. The inhibitory effect of HA glycopolymers on hyaluronidase (HAase) activity was also investigated suggesting GlcNAc- and GlcA-based glycopolymers as potential HAase inhibitors. Glycopolymers based on hyaluronan (HA) were synthesised as homopolymers and alternating copolymers and used as probes to study the interactions with known HA-binding proteins and peptides. |
| Databáze: | OpenAIRE |
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