Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus ty

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. Oligosaccharides displayed at cell surfaces have important biological functions — such as controlling the entry of viruses — but a full understanding of this behaviour requires the synthesis of such compounds, which remains challenging. Here, two synthetic octasaccharides were shown to have remarkably similar inhibition of herpes simplex virus type 1 infection of cell cultures to the natural oligosaccharide identified in enzymatic studies.

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Hu, YP., Lin, SY., Huang, CY. et al. Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus type 1 host–cell interaction. Nature Chem 3, 557–563 (2011). https://doi.org/10.1038/nchem.1073

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