Novel trivalent anti-influenza reagent
Novel trivalent anti-influenza reagent
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DOI：
10.1016/j.bmcl.2010.04.060
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发表时间：
2010-06-15
影响因子：
2.7
通讯作者：
Nishimura, Shin-Ichiro
中科院分区：
文献类型：
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作者：
Feng, Fei;Miura, Nobuaki;Nishimura, Shin-Ichiro
我们设计并合成了新型三价抗流感病毒试剂。唾液酸乳糖位于每个价的末端，旨在阻断病毒表面上的血凝素（HA）三聚体的每个受体结合位点。结构分析进行了一个模型，这是用计算机模拟构建。先前报道的环状糖肽阻断剂[Ohta，T.; Miura，N.; Fujitani，N.; Nakajima，F.; Niikura，K.; Sadamoto，R.;郭，C.- T.; Suzuki，T.; Suzuki，Y.; Monde，K.; Nishimura，S.- I. Angew.化学国际版，2003，42，5186]结合到模型中的HA。分析表明，带有Neu 5A α 2，3Gal β 1，4Glc三糖的环肽中的谷氨酰胺残基通过接头与HA中的Gln 189通过氢键相互作用。本发明的抗流感试剂可能与Gln 189附近包含的谷氨酰胺残基相互作用。在MDCK细胞中进行流感病毒A/PR/8/1934（H1N1）的鼠疫减少测定，以评价合成的化合物抑制病毒复制。其中一种化合物在4 ℃下浓度为400 μ M时显示出约85%的抑制作用。(C)2010爱思唯尔有限公司版权所有。
We designed and synthesized novel trivalent anti-influenza reagents. Sialyllactose was located at the terminal of each valence which aimed to block each receptor-binding site of the hemagglutinin (HA) trimer on the surface of the virus. Structural analyses were carried out with a model which was constructed with a computer simulation. A previously reported cyclic glycopeptide blocker [Ohta, T.; Miura, N.; Fujitani, N.; Nakajima, F.; Niikura, K.; Sadamoto, R.; Guo, C.-T.; Suzuki, T.; Suzuki, Y.; Monde, K.; Nishimura, S.-I. Angew. Chem. Int. Ed., 2003, 42, 5186] bound to the HA in the model. The analyses suggest that the glutamine residue in the cyclic peptide bearing Neu5A alpha 2,3Gal beta 1,4Glc trisaccharide via a linker interacts with the Gln189 in HA through hydrogen bonding. The present anti-influenza reagents likely interact with a glutamine residue included in the vicinity of Gln189. A plague reduction assay of the influenza virus, A/PR/8/1934 (H1N1),was performed in MDCK cells to evaluate for the synthesized compounds to inhibit viral replication. One of the compounds showed approximately 85% inhibition at the concentration of 400 mu M at 4 degrees C. (C) 2010 Elsevier Ltd. All rights reserved.