期刊
BIOCHEMISTRY
卷 47, 期 21, 页码 5774-5783出版社
AMER CHEMICAL SOC
DOI: 10.1021/bi800205t
关键词
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资金
- NCRR NIH HHS [R41 RR023764-02, R41 RR023764] Funding Source: Medline
- NHLBI NIH HHS [R01 HL062244, R01 HL062244-05A1, R01 HL062244-07, HL62244, R01 HL052622-05, R01 HL052622] Funding Source: Medline
- NIAID NIH HHS [R01 AI050050, AI50050, AI057860, R01 AI050050-06, R01 AI057860] Funding Source: Medline
- NIGMS NIH HHS [R01 GM038060, GM38060, R01 GM038060-19] Funding Source: Medline
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 Delta UA2S-GleNS6S-IdoUA2S-GIcNS6S-IdoUA2S-GIcNS3S6S-IdoUA2S-GIcNS6S (where Delta UA 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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