Synthesis of 3-O-Sulfated Heparan Sulfate Oligosaccharides Using 3-O-Sulfotransferase Isoform 4

• DOI: 10.1021/acschembio.1c00474
• Publication Date: 2021-08-05T20:31:10Z
• Authors: Jine Li; Guowei Su; Yongmei Xu; Katelyn Arnold; Vijayakanth Pagadala; Chunyu Wang; Jian Liu
• Keywords: Sulfotransferase; Oligosaccharide; Iduronic acid

Heparan sulfate (HS) 3-O-sulfotransferase isoform 4 (3-OST-4) is a specialized carbohydrate sulfotransferase participating in the biosynthesis of heparan sulfate. Here, we report expression and purification recombinant 3-OST-4 enzyme use it for synthesis library 3-O-sulfated hexasaccharides octasaccharides. The unique structural feature that each oligosaccharide contains disaccharide domain with 2-O-sulfated glucuronic acid (GlcA2S) glucosamine (GlcNS3S). By rearranging order enzymatic modification steps, demonstrate oligosaccharides different saccharide sequences. characterization was completed by electrospray ionization mass spectrometry NMR. These show weak to very anti-Factor Xa activity, measurement anticoagulant activity. We discovered HSoligo 7 (HS 7), octasaccharide, binds high mobility group box 1 protein (HMGB1) tau protein, both believed be involved process inflammation. Access expands capability chemoenzymatic method synthesize novel oligosaccharides. will become valuable reagents probe biological functions HS develop HS-based therapeutic agents.