Genomics Research Center, Academia Sinica, 128, Section 2, Academia Road, Taipei 115, Taiwan.
Nat Chem. 2011 Jun 19;3(7):557-63. doi: 10.1038/nchem.1073.
Cell surface carbohydrates play significant roles in a number of biologically important processes. Heparan sulfate, for instance, is a ubiquitously distributed polysulfated polysaccharide that is involved, among other things, in the initial step of herpes simplex virus type 1 (HSV-1) infection. The virus interacts with cell-surface heparan sulfate to facilitate host-cell attachment and entry. 3-O-Sulfonated heparan sulfate has been found to function as an HSV-1 entry receptor. Achieving a complete understanding of these interactions requires the chemical synthesis of such oligosaccharides, but this remains challenging. Here, we present a convenient approach for the synthesis of two irregular 3-O-sulfonated heparan sulfate octasaccharides, making use of a key disaccharide intermediate to acquire different building blocks for the oligosaccharide chain assembly. Despite substantial structural differences, the prepared 3-O-sulfonated sugars blocked viral infection in a dosage-dependent manner with remarkable similarity to one another.
细胞表面碳水化合物在许多重要的生物学过程中发挥着重要作用。例如，硫酸乙酰肝素是一种广泛分布的多硫酸化多糖，除其他外，它参与单纯疱疹病毒 1 型 (HSV-1) 感染的初始步骤。该病毒与细胞表面硫酸乙酰肝素相互作用，以促进宿主细胞附着和进入。已经发现 3-O-磺化硫酸乙酰肝素作为 HSV-1 进入受体发挥作用。要完全了解这些相互作用，需要对这些寡糖进行化学合成，但这仍然具有挑战性。在这里，我们提出了一种方便的方法来合成两种不规则的 3-O-磺化硫酸乙酰肝素八糖，利用关键的二糖中间体获得寡糖链组装的不同构建块。尽管存在显著的结构差异，但所制备的 3-O-磺化糖以剂量依赖的方式阻断病毒感染，彼此之间具有惊人的相似性。
