Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge, CB2 1EW, U.K.
Biochemistry. 2013 Dec 23;52(51):9269-74. doi: 10.1021/bi401270d. Epub 2013 Dec 10.
RNA-protein interactions are vital throughout the HIV-1 life cycle for the successful production of infectious virus particles. One such essential RNA-protein interaction occurs between the full-length genomic viral RNA and the major structural protein of the virus. The initial interaction is between the Gag polyprotein and the viral RNA packaging signal (psi or Ψ), a highly conserved RNA structural element within the 5'-UTR of the HIV-1 genome, which has gained attention as a potential therapeutic target. Here, we report the application of a target-based assay to identify small molecules, which modulate the interaction between Gag and Ψ. We then demonstrate that one such molecule exhibits potent inhibitory activity in a viral replication assay. The mode of binding of the lead molecules to the RNA target was characterized by ¹H NMR spectroscopy.
RNA-蛋白质相互作用在 HIV-1 生命周期的各个阶段对于成功产生感染性病毒颗粒至关重要。这种必不可少的 RNA-蛋白质相互作用发生在全长基因组病毒 RNA 和病毒的主要结构蛋白之间。最初的相互作用发生在 Gag 多蛋白和病毒 RNA 包装信号（psi 或 Ψ）之间，这是 HIV-1 基因组 5'UTR 中高度保守的 RNA 结构元件，已作为潜在的治疗靶点引起关注。在这里，我们报告了应用基于靶标的测定法来鉴定调节 Gag 和 Ψ 之间相互作用的小分子。然后，我们证明了其中一种分子在病毒复制测定中表现出很强的抑制活性。通过 ¹H NMR 光谱学表征了先导分子与 RNA 靶标的结合模式。
