Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus type 1 host-cell interaction

Nat Chem. 2011 Jun 19;3(7):557-63. doi: 10.1038/nchem.1073.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Chlorocebus aethiops
  • Drug Design*
  • Heparitin Sulfate / chemical synthesis*
  • Heparitin Sulfate / chemistry
  • Heparitin Sulfate / pharmacology*
  • Herpesvirus 1, Human / drug effects*
  • Host-Pathogen Interactions / drug effects*
  • Humans
  • Molecular Structure
  • Oligosaccharides / chemical synthesis*
  • Oligosaccharides / chemistry
  • Oligosaccharides / pharmacology
  • Receptors, Cell Surface / chemistry
  • Sulfones / chemistry*
  • Vero Cells

Substances

  • Antiviral Agents
  • Oligosaccharides
  • Receptors, Cell Surface
  • Sulfones
  • Heparitin Sulfate

Associated data

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