Hyaluronan (HA)-inspired glycopolymers as molecular tools for studying HA functions

Dominic W.P. Collis, Gokhan Yilmaz, Yichen Yuan, Alessandra Monaco, Guy Ochbaum, Yejiao Shi, Clare O'Malley, Veselina Uzunova, Richard Napier, Ronit Bitton, C. Remzi Becer, Helena S. Azevedo

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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. This journal is

Original languageEnglish
Pages (from-to)568-576
Number of pages9
JournalRSC Chemical Biology
Volume2
Issue number2
DOIs
StatePublished - 1 Apr 2021

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Chemistry (miscellaneous)

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