Details

Autor(en) / Beteiligte

• Sun, Lifeng
• Chopra, Pradeep
• Boons, Geert‐Jan

Titel

Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides having a Domain Structure

Ist Teil von

• Angewandte Chemie (International ed.), 2022-11, Vol.61 (47), p.e202211112-n/a

Auflage

International ed. in English

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Well‐defined heparan sulfate mimetics having a domain structure were synthesized by copper catalyzed alkyne‐azide cycloaddition of HS oligosaccharide having a terminal alkyne or azide moiety. Competition binding experiments demonstrated that the length of NA domains modulates the binding of the chemokines CCL5 and CXCL8.