Open AccessSynthesis of 3-O-Sulfated Heparan Sulfate Oligosaccharides Using 3-O-Sulfotransferase Isoform 4
Author(s) -
Jine Li,
Guowei Su,
Yongmei Xu,
Katelyn Arnold,
Vijayakanth Pagadala,
Chunyu Wang
Publication year - 2021
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/acschembio.1c00474
Subject(s) - sulfation , heparan sulfate , sulfotransferase , chemistry , oligosaccharide , iduronic acid , biochemistry , glucuronic acid , glycosaminoglycan , polysaccharide
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 the expression and purification of the recombinant 3-OST-4 enzyme and use it for the synthesis of a library of 3- O -sulfated hexasaccharides and 3- O -sulfated octasaccharides. The unique structural feature of the library is that each oligosaccharide contains a disaccharide domain with a 2- O -sulfated glucuronic acid (GlcA2S) and 3- O -sulfated glucosamine (GlcNS3S). By rearranging the order of the enzymatic modification steps, we demonstrate the synthesis of oligosaccharides with different saccharide sequences. The structural characterization was completed by electrospray ionization mass spectrometry and NMR. These 3- O -sulfated oligosaccharides show weak to very weak anti-Factor Xa activity, a measurement of anticoagulant activity. We discovered that HSoligo 7 (HS oligosaccharide 7 ), a 3- O -sulfated octasaccharide, binds to high mobility group box 1 protein (HMGB1) and tau protein, both believed to be involved in the process of inflammation. Access to the recombinant 3-OST-4 expands the capability of the chemoenzymatic method to synthesize novel 3- O -sulfated oligosaccharides. The oligosaccharides will become valuable reagents to probe the biological functions of 3- O -sulfated HS and to develop HS-based therapeutic agents.