Copeland R, Balasubramaniam A, Tiwari V, Zhang F, Bridges A, Linhardt RJ, Shukla D, Liu J
Using a 3-O-Sulfated Heparin Octasaccharide To Inhibit the Entry of Herpes Simplex Virus Type 1. [JOURNAL ARTICLE]
Biochemistry 2008 May 6.
Heparan sulfate (HS) is a highly sulfated polysaccharide and is present in large quantities on the cell surface and in the extracellular matrix. Herpes simplex virus type 1 (HSV-1) utilizes a specialized cell surface HS, known as 3- O-sulfated HS, as an entry receptor to establish infection. Here, we exploit an approach to inhibiting HSV-1 infection by using a 3- O-sulfated octasaccharide, mimicking the active domain of the entry receptor. The 3- O-sulfated octasaccharide was synthesized by incubating a heparin octasaccharide (3-OH octasaccharide) with HS 3- O-sulfotransferase isoform 3. The resultant 3- O-sulfated octasaccharide has a structure of DeltaUA2S-GlcNS6S-IdoUA2S-GlcNS6S-IdoUA2S-GlcNS3S6S-IdoUA2S-GlcNS6S (where DeltaUA is 4-deoxy-alpha- l- threo-hex-4-enopyranosyluronic acid, GlcN is d-glucosamine, and IdoUA is l-iduronic acid). Results from cell-based assays revealed that the 3- O-sulfated octasaccharide has stronger activity in blocking HSV-1 infection than that of the 3-OH octasaccharide, suggesting that the inhibition of HSV-1 infection requires a unique sulfation moiety. Our results suggest the feasibility of inhibiting HSV-1 infection by blocking viral entry with a specific oligosaccharide.
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