Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides having a Domain Structure

Lifeng Sun, Pradeep Chopra, Geert-Jan Boons

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Heparan sulfate (HS) has a domain structure in which regions that are modified by epimerization and sulfonation (NS domains) are interspersed by unmodified fragments (NA domains). There is data to support that domain organization of HS can regulate binding of proteins, however, such model has been difficult to probe. Here, we report a chemoenzymatic methodology that can provide HS oligosaccharides composed of two or more NS domains separated by NA domains of different length. It is based on the chemical synthesis of a HS oligosaccharide that enzymatically was extended by various GlcA-GlcNAc units and terminated in GlcNAc having an azido moiety at C-6 position. HS oligosaccharides having an azide and alkyne moiety could be assembled by copper catalyzed alkyne-azide cycloaddition to give compounds having various NS domains separated by unsulfonated regions. Competition binding studies showed that the length of an NA domain modulates the binding of the chemokines CCL5 and CXCL8.

Original languageEnglish
Article numbere202211112
Pages (from-to)1-9
JournalAngewandte Chemie-International Edition
Volume61
Issue number47
Early online date23 Sept 2022
DOIs
Publication statusPublished - 21 Nov 2022

Keywords

  • Carbohydrates
  • Chemokine
  • Enzyme Catalysis
  • Glycomimetic
  • Glycosylation

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