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首页> 外文期刊>Antiviral chemistry & chemotherapy >Mesoionic heterocyclic compounds as candidate messenger RNA cap analogue inhibitors of the influenza virus RNA polymerase cap-binding activity.
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Mesoionic heterocyclic compounds as candidate messenger RNA cap analogue inhibitors of the influenza virus RNA polymerase cap-binding activity.

机译：中性杂环化合物作为流感病毒RNA聚合酶帽结合活性的候选信使RNA帽类似物抑制剂。

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摘要

BACKGROUND: An unusual feature of influenza viral -messenger RNA (mRNA) synthesis is its dependence upon host cell mRNAs as a source of capped RNA primers. A crucial activity of the influenza polymerase is to steal these primers by binding and cleaving the caps from host mRNAs. The recent structural analysis of the cap-binding fragment of the influenza virus PB2 protein has highlighted the importance of the mesoionic properties of the N7-methylguanine (N(7m)G) component of the mRNA cap in this interaction. METHODS: A series of mesoionic heterocycles with 5,6-fused ring systems analogous to the N(7m)G component of mRNA cap structures were synthesized and examined for the ability to inhibit the cap-binding activity of the influenza virus RNA polymerase complex using a bead-based in vitro cap-binding assay. RESULTS: None of the compounds tested were able to significantly inhibit binding and subsequent endonucleolytic cleavage of a synthetic radiolabelled capped mRNA substrate by recombinant influenza virus polymerase in vitro. CONCLUSIONS: Compounds analogous to the mesoionic N(7m)G component of mRNA cap structures comprise a large class of potential inhibitors of the influenza virus polymerase. Although this preliminary assessment of a small group of related analogues was unsuccessful, further screening of this class of compounds is warranted.
机译：背景：流感病毒信使RNA（mRNA）合成的不寻常特征是其依赖宿主细胞mRNAs作为封端RNA引物的来源。流感聚合酶的一项关键活动是通过结合并从宿主mRNA上切割帽来窃取这些引物。流感病毒PB2蛋白的帽结合片段的最新结构分析突出了在这种相互作用中，mRNA帽的N7-甲基鸟嘌呤（N（7m）G）组分的介电特性的重要性。方法：合成一系列具有5,6-稠环系统的介导杂环，类似于mRNA帽结构的N（7m）G成分，并使用以下方法检测其抑制流感病毒RNA聚合酶帽结合活性的能力。基于珠的体外帽结合测定。结果：测试的化合物均不能在体外通过重组流感病毒聚合酶显着抑制合成放射标记的带帽mRNA底物的结合和随后的核酸内切裂解。结论：类似于mRNA帽结构的中性N（7m）G成分的化合物包含一类潜在的流感病毒聚合酶抑制剂。尽管对一小组相关类似物的初步评估没有成功，但仍需进一步筛选此类化合物。

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