靶向HIV-1 TAR RNA环的环状和发夹PNAs抑制HIV复制

IF 1.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Journal of Nucleic Acids Pub Date : 2012-01-01 Epub Date: 2012-09-17 DOI:10.1155/2012/591025
Gregory Upert, Audrey Di Giorgio, Alok Upadhyay, Dinesh Manvar, Nootan Pandey, Virendra N Pandey, Nadia Patino
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引用次数: 10

摘要

人类免疫缺陷病毒-1 (HIV-1)的复制和基因表达需要病毒蛋白Tat与其交互激活应答元件(TAR)的特异性相互作用,形成高度稳定的茎突环结构。之前,我们描述了基于三苯基磷(TPP)阳离子的载体,可以有效地将核苷酸类似物(PNAs)递送到细胞的细胞质中。特别是,我们发现,在体外和细胞培养系统中,针对TAR的顶端茎环区域的线性16聚PNA的TPP偶联物阻碍了tat介导的HIV-1 LTR的转激活。在这篇文章中,我们将TPP与靶向HIV-1 TAR环区的环状和发夹状PNAs结合,并在细胞培养系统中评估了它们的抗病毒效果。我们发现,与含有12或16个残基的发夹PNAs相比,仅含有8个残基的tpp环状PNAs表现出更高的抗病毒效力。我们进一步注意到,8-聚环状PNA和16-聚线性PNA的tpp偶联物表现出相似的抗病毒效果。然而,环状PNAs被证明对其靶序列具有高度特异性。这篇文章强调了小的受限环状PNAs在线性和发夹结构上对靶向生物学相关RNA发夹的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Inhibition of HIV Replication by Cyclic and Hairpin PNAs Targeting the HIV-1 TAR RNA Loop.

Inhibition of HIV Replication by Cyclic and Hairpin PNAs Targeting the HIV-1 TAR RNA Loop.

Inhibition of HIV Replication by Cyclic and Hairpin PNAs Targeting the HIV-1 TAR RNA Loop.

Inhibition of HIV Replication by Cyclic and Hairpin PNAs Targeting the HIV-1 TAR RNA Loop.

Human immunodeficiency virus-1 (HIV-1) replication and gene expression entails specific interaction of the viral protein Tat with its transactivation responsive element (TAR), to form a highly stable stem-bulge-loop structure. Previously, we described triphenylphosphonium (TPP) cation-based vectors that efficiently deliver nucleotide analogs (PNAs) into the cytoplasm of cells. In particular, we showed that the TPP conjugate of a linear 16-mer PNA targeting the apical stem-loop region of TAR impedes Tat-mediated transactivation of the HIV-1 LTR in vitro and also in cell culture systems. In this communication, we conjugated TPP to cyclic and hairpin PNAs targeting the loop region of HIV-1 TAR and evaluated their antiviral efficacy in a cell culture system. We found that TPP-cyclic PNAs containing only 8 residues, showed higher antiviral potency compared to hairpin PNAs of 12 or 16 residues. We further noted that the TPP-conjugates of the 8-mer cyclic PNA as well as the 16-mer linear PNA displayed similar antiviral efficacy. However, cyclic PNAs were shown to be highly specific to their target sequences. This communication emphasizes on the importance of small constrained cyclic PNAs over both linear and hairpin structures for targeting biologically relevant RNA hairpins.

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来源期刊
Journal of Nucleic Acids
Journal of Nucleic Acids BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
3.10
自引率
21.70%
发文量
5
审稿时长
12 weeks
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