Using a 3-O-Sulfated Heparan Sulfate Octasaccharide to Inhibit the Entry of Herpes Simplex Virus 1

Copeland, R.
Balasubramaniam, A.
Tiwari, Vaibhav
Zhang, F.
Bridges, A.
Linhardt, Robert J.
Shukla, D.
Liu, J.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Using a 3-O-Sulfated Heparan Sulfate Octasaccharide to Inhibit the Entry of Herpes Simplex Virus 1, R. Copeland, A. Balasubramaniam, V. Tiwari, F. Zhang, A. Bridges, R. J. Linhardt, D. Shukla, J. Liu, Biochemistry, 47, 5774–5783, 2008.
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 inhibit 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 ΔUA2S-GlcNS6S-IdoUA2S-GlcNS6S-IdoUA2S-GlcNS3S6S-IdoUA2S-GlcNS6S (where ΔUA is 4-deoxy-α-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.
Biochemistry, 47, 5774–5783
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
American Chemical Society (ACS)
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
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