Using a 3-O-sulfated heparin octasaccharide to inhibit the entry of herpes simplex virus type 1
Using a 3-O-sulfated heparin octasaccharide to inhibit the entry of herpes simplex virus type 1
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DOI：
10.1021/bi800205t
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发表时间：
2008-05-27
期刊：
影响因子：
2.9
通讯作者：
Liu, Jian
中科院分区：
文献类型：
--
作者：
Copeland, Ronald;Balasubramaniam, Arun;Liu, Jian
硫酸乙酰肝素(HS)是一种高度硫酸化的多糖，大量存在于细胞表面和细胞外基质中。单纯疱疹病毒1型(HSV-1)利用一种特殊的细胞表面HS，称为3-O-硫酸HS，作为进入受体来确定感染。在这里，我们开发了一种方法，通过使用3-O-硫酸盐八糖，模拟进入受体的活性区域来抑制HSV-1感染。肝素八糖(3-OH八糖)与HS3-O-磺基转移酶亚型3温育得到3-O-磺化八糖，其结构为Delta UA2S-GleNS6S-IdoUA2S-GIcNS6S-IdoUA2S-GIcNS3S6S-IdoUA2S-GIcNS6S(其中Delta UA为4-deoxy-alpha-L-threo-hex-4-enopyranosyluronic酸，GlcN为D-氨基葡萄糖，IdoUA为L-艾杜糖醛酸)。细胞检测结果表明，3-O-磺化八糖比3-羟基八糖具有更强的阻断HSV-1感染的活性，提示抑制HSV-1感染需要一种独特的硫化部分。我们的结果表明，通过用特定的寡糖阻断病毒进入来抑制HSV-1感染是可行的。
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.