title: Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus type 1 host-cell interaction.
abstract: Cell surface carbohydrates play significant roles in a number of biologically important processes. Heparan sulfate, for instance, is a ubiquitously distributed polysulfated polysaccharide that is involved, among other things, in the initial step of herpes simplex virus type 1 (HSV-1) infection. The virus interacts with cell-surface heparan sulfate to facilitate host-cell attachment and entry. 3-O-Sulfonated heparan sulfate has been found to function as an HSV-1 entry receptor. Achieving a complete understanding of these interactions requires the chemical synthesis of such oligosaccharides, but this remains challenging. Here, we present a convenient approach for the synthesis of two irregular 3-O-sulfonated heparan sulfate octasaccharides, making use of a key disaccharide intermediate to acquire different building blocks for the oligosaccharide chain assembly. Despite substantial structural differences, the prepared 3-O-sulfonated sugars blocked viral infection in a dosage-dependent manner with remarkable similarity to one another.
authors.affiliation: Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei 115, Taiwan.
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Hu
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Lin
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Huang
authors.forename: Medel Manuel L
authors.initials: MM
authors.lastname: Zulueta
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Chang
authors.forename: Shang-Cheng
authors.initials: SC
authors.lastname: Hung
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002522:Chlorocebus aethiops; D015195:Drug Design; D006497:Heparan Sulfate / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000737:chemistry; D013450:Sulfones / Q000737:chemistry*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D006497:Heparan Sulfate; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D013450:Sulfones