title: Discovery of a heparan sulfate 3-O-sulfation specific peeling reaction.
abstract: Heparan sulfate (HS) 3-O-sulfation determines the binding specificity of HS/heparin for antithrombin III and plays a key role in herpes simplex virus (HSV) infection. However, the low natural abundance of HS 3-O-sulfation poses a serious challenge for functional studies other than the two cases mentioned above. By contrast, multiple distinct isoforms of 3-O-sulfotranserases exist in mammals (up to seven isoenzymes). Here we describe a novel peeling reaction that specifically degrades HS chains with 3-O-sulfated glucosamine at the reducing-end. When HS/heparin is enzymatically depolymerized for compositional analysis, 3-O-sulfated glucosamine at the reducing ends appears to be susceptible to degradation under mildly basic conditions. We propose a 3-O-desulfation initiated peeling reaction mechanism based on the intermediate and side-reaction products observed. Our discovery calls for the re-evaluation of the natural abundance and functions of HS 3-O-sulfation by taking into consideration the negative impact of this novel peeling reaction.
authors.affiliation: Department of Biochemistry, Boston University Medical Campus , 670 Albany Street, Boston, Massachusetts 02118, United States.
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Yang
authors.initials: Y
authors.lastname: Mao
authors.forename: Chengli
authors.initials: C
authors.lastname: Zong
authors.forename: Cheng
authors.initials: C
authors.lastname: Lin
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Boons
authors.forename: Joseph
authors.initials: J
authors.lastname: Zaia
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D009844:Oligosaccharides / Q000378:metabolism; D011485:Protein Binding; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism*; D015238:Sulfotransferases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D005944:Glucosamine; D006493:Heparin; D006497:Heparan Sulfate; D009844:Oligosaccharides; D013431:Sulfates; D015238:Sulfotransferases; C065632:glucosamine 3-O-sulfate