| Title | Using a 3-O-Sulfated Heparin Octasaccharide To Inhibit the Entry of Herpes Simplex Virus Type 1. | | Author(s) | Copeland R, Balasubramaniam A, Tiwari V, Zhang F, Bridges A, Linhardt RJ, Shukla D, Liu J | | Institution | Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, Division of Molecular Pharmaceutics, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, Department of Ophthalmology and Visual Sciences and Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, and Departments of Chemistry and Chemical Biology, Biology, and Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180 jian_liu@unc.edu. | | Source | Biochemistry 2008 May 6. | | 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 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18457417 |
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