Antisense-lnduced Guanine Quadruplexes Inhibit Reverse ranscription by HlV-1 Reverse Transcriptase

Masaki Hagihara; Lisa Yamauchi; Akiko Seo; Keisuke Yoneda; Mayo Senda; Kazuhiko Nakatani

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Antisense-lnduced Guanine Quadruplexes Inhibit Reverse ranscription by HlV-1 Reverse Transcriptase

机译：反义诱导鸟嘌呤四联体抑制HiV-1逆转录酶逆转录。

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Guanine quadruplex structures in DNA and RNA affect normal cellular processes such as replication, recombination, and translation. Thus, controlling guanine quadruplex structures could make it possible to manipulate the biological function of nucleic acids. Here, we report a novel antisense strategy using guanine-tethered antisense oligonucleotides (g-ASs) that introduces an RNA-DNA heteroquadruplex structure on RNA templates in a predictable and sequence-specific manner, which in practice effectively inhibited reverse transcription on a variety of RNA sequences, including the HIV-1 RNA genome. Reverse transcriptase-mediated enzymatic analysis, together with other biophysical analyses, elucidated a cooperative binding of duplex and quadruplex in g-AS-RNA complexes. The remarkable ability of g-ASs to inhibit reverse transcription could make possible the development of novel anti-retroviral gene therapies based on blocking the replication of RNA genomes to complementary DNA, which is a critical step for integration into the host's genome.

机译：DNA和RNA中的鸟嘌呤四链体结构会影响正常的细胞过程，如复制，重组和翻译。因此，控制鸟嘌呤四链体结构可使操纵核酸的生物学功能成为可能。在这里，我们报告了一种新的使用鸟嘌呤束缚的反义寡核苷酸（g-ASs）的反义策略，该策略以可预测和特定于序列的方式在RNA模板上引入了RNA-DNA异四倍体结构，在实践中有效地抑制了多种RNA序列，包括HIV-1 RNA基因组。逆转录酶介导的酶分析以及其他生物物理分析，阐明了g-AS-RNA复合物中双链体和四链体的协同结合。 g-AS具有显着的抑制逆转录的能力，从而有可能基于阻止RNA基因组复制到互补DNA的基础上开发出新的抗逆转录病毒基因疗法，这是整合到宿主基因组中的关键步骤。

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《Journal of the American Chemical Society》 |2010年第32期|p.11171-11178|共8页
作者
Masaki Hagihara; Lisa Yamauchi; Akiko Seo; Keisuke Yoneda; Mayo Senda; Kazuhiko Nakatani;
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作者单位

Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Osaka, Japan;

rnDepartment of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Osaka, Japan;

rnDepartment of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Osaka, Japan;

rnDepartment of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Osaka, Japan;

rnDepartment of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Osaka, Japan;

rnDepartment of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Osaka, Japan;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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1. Antisense-Induced Guanine Quadruplexes Inhibit Reverse Transcription by HIV-1 Reverse Transcriptase [J] . Masaki Hagihara Lisa Yamauchi Akiko Seo Keisuke Yoneda Mayo Senda and Kazuhiko Nakatani Journal of the American Chemical Society . 2010,第32期

机译：反义诱导鸟嘌呤四联体抑制HIV-1逆转录酶逆转录。
2. Nucleoside reverse transcriptase inhibitor-sparing regimen (nonnucleoside reverse transcriptase inhibitor + protease inhibitor) was more likely associated with resistance comparing to nonnucleoside reverse transcriptase inhibitor or protease inhibitor + nucleoside reverse transcriptase inhibitor in the randomized ANRS 121 trial. [J] . Soulie C, Assoumou L, Ghosn J AIDS . 2009,第12期

机译：在随机ANRS 121试验中，与非核苷类逆转录酶抑制剂或蛋白酶抑制剂+核苷类逆转录酶抑制剂相比，保留核苷类逆转录酶抑制剂的方案（非核苷类逆转录酶抑制剂+蛋白酶抑制剂）更可能与耐药相关。
3. Simultaneous quantification of a non-nucleoside reverse transcriptase inhibitor efavirenz, a nucleoside reverse transcriptase inhibitor emtricitabine and a nucleotide reverse transcriptase inhibitor tenofovir in plasma by liquid chromatography positive ion electrospray tandem mass spectrometry. [J] . Nirogi R, Bhyrapuneni G, Kandikere V Biomedical Chromatography: An International Journal Devoted to Research in Chromatographic Methodologies and Their Applications in the Biosciences . 2009,第4期

机译：通过液相色谱正离子电喷雾串联质谱法同时定量测定血浆中的非核苷类逆转录酶抑制剂依非韦伦，核苷类逆转录酶抑制剂恩曲他滨和核苷酸类逆转录酶抑制剂替诺福韦。
4. The Combination of Inhibitors of Lymphocyte Activation Hydroxyurea (HU), Didox (DX), and Trimidox (TX)) in Combination with the Reverse Transcriptase Inhibitors (RTI): Abacavir (ABC), Didanosine (ddI), and Tenofovir (TFV) in the Murine Model of Immun [C] . R. Sumpter, M. Inayat, C. Mayhew International AIDS Conference . 2004

机译：淋巴细胞活化羟基脲（HU），牛（DX）和三苯并（TX）的抑制剂的组合与逆转录酶抑制剂（RTI）组合：ABACAVIR（ABC），脱氨酸（DDI）和替诺福韦（TFV） IMMUN的鼠模型
5. Mechanisms by which nonnucleoside reverse transcriptase inhibitors block HIV-1 replication alone and in combination with other reverse transcriptase inhibitors [D] . Radzio, Jessica Ann 2010

机译：非核苷类逆转录酶抑制剂单独或与其他逆转录酶抑制剂合用可阻断HIV-1复制的机制
6. Structural insights into the recognition of nucleoside reverse transcriptase inhibitors by HIV‐1 reverse transcriptase: First crystal structures with reverse transcriptase and the active triphosphate forms of lamivudine and emtricitabine [O] . Nicole Bertoletti, Albert H. Chan, Raymond F. Schinazi, 2019

机译：通过HIV-1逆转录酶的结构见解核苷逆转录酶抑制剂：具有逆转录酶的第一晶体结构和Lamivudine和Emtrickamine的活性三磷酸酯形式
7. Impact of reverse transcriptase resistance on the efficacy of TMC125 (etravirine) with two nucleoside reverse transcriptase inhibitors in protease inhibitor-naïve, nonnucleoside reverse transcriptase inhibitor-experienced patients: study TMC125-C227* [O] . K Ruxrungtham, RJ Pedro, GH Latiff, 2008

机译：逆转录酶抗性对TMC125（etravirine）的疗效对蛋白酶抑制剂中的核苷逆转录酶抑制剂的影响 - 抗核苷逆转录酶抑制剂，无核苷逆转录酶抑制剂 - 经验丰富的患者：研究TMC125-C227 *

Antisense-lnduced Guanine Quadruplexes Inhibit Reverse ranscription by HlV-1 Reverse Transcriptase

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