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Sialyllactose-Modified Three-Way Junction DNA as Binding Inhibitor of Influenza Virus Hemagglutinin
Bioconjugate Chemistry ( IF 4.7 ) Pub Date : 2018-03-22 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00045
Miyuki Yamabe 1 , Kunihiro Kaihatsu 2 , Yasuhito Ebara 1
Affiliation  

Sialic acid present on the cell surface is recognized by hemagglutinin (HA) on the influenza virus in the first step of infection. Therefore, a compound that can efficiently interfere with the interaction between sialic acid and HA might inhibit infection and allow detection of the influenza virus. We focused on the spatial arrangement of sialic acid binding sites on HA and developed 2,3-sialyllactose (2,3-SL)-modified three-way junction (3WJ) DNA molecules with a topology similar to that of sialic acid binding sites. 3WJ DNA with three 2,3-SL residues on each DNA strand showed (8.0 × 104)-fold higher binding affinity for influenza virus A/Puerto Rico/08/34 (H1N1) compared to the 2,3-SL. This result indicated that the glycocluster effect due to clustering on one DNA arm and optimal spatial arrangement of the 3WJ DNA improved the weak interactions between a sialic acid and its binding site on HA. This 3WJ DNA compound has possible application as an inhibitor of influenza infection and for virus sensing.

中文翻译:

唾液酸乳糖修饰的三向连接DNA作为流感病毒血凝素的结合抑制剂

在感染的第一步,存在于细胞表面的唾液酸被流感病毒上的血凝素(HA)识别。因此,可以有效干扰唾液酸和HA之间相互作用的化合物可以抑制感染并可以检测流感病毒。我们专注于HA上唾液酸结合位点的空间排列,并开发了具有类似于唾液酸结合位点的拓扑结构的2,3-唾液酸乳糖(2,3-SL)修饰的三向连接(3WJ)DNA分子。在每个DNA链上带有3个2,3-SL残基的3WJ DNA显示(8.0×10 4与2,3-SL相比,对A / Puerto Rico / 08/34(H1N1)流感病毒的结合亲和力高1倍。该结果表明,由于在一个DNA臂上聚集和3WJ DNA的最佳空间排列而引起的糖簇作用改善了唾液酸与其在HA上的结合位点之间的弱相互作用。该3WJ DNA化合物可能会用作流感感染的抑制剂和病毒感测。
更新日期:2018-03-22
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