Using a 3-O-Sulfated Heparan Sulfate Octasaccharide to Inhibit the Entry of Herpes Simplex Virus 1
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Authors
Copeland, R.
Balasubramaniam, A.
Tiwari, Vaibhav
Zhang, F.
Bridges, A.
Linhardt, Robert J.
Shukla, D.
Liu, J.
Issue Date
2008
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
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.
Description
Biochemistry, 47, 5774–5783
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
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.
Publisher
American Chemical Society (ACS)