• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

LTR-III 中的四重态-二联体连接：对与 BMH-21、奈拉滨和阿霉素复合物的分子洞察。

Quadruplex-duplex junction in LTR-III: A molecular insight into the complexes with BMH-21, namitecan and doxorubicin.

机构信息

Department of Food, Environmental and Nutritional Sciences (DEFENS), University of Milan, Milan, Italy.

Scientia Advice di Roberto Artali, Cesano Maderno (MB), Italy.

出版信息

PLoS One. 2024 Jul 24;19(7):e0306239. doi: 10.1371/journal.pone.0306239. eCollection 2024.

DOI:10.1371/journal.pone.0306239
PMID:39046961
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11268700/
Abstract

Quadruplex-Duplex (Q-D) junctions are unique structural motifs garnering increasing interest as drug targets, due to their frequent occurrence in genomic sequences. The viral HIV LTR-III sequence was chosen as a Q-D junction model to study the affinity of the selected compounds BMH-21, namitecan (ST-1968), and doxorubicin (DOXO), all containing a planar polycyclic aromatic moiety, linked to either one short aminoalkyl or an aminoglycosyl group. A multidisciplinary approach that combines NMR spectroscopy, molecular modelling, circular dichroism (CD) and fluorescence spectroscopy was employed. The studied ligands induced moderate but clear stabilization to the Q-D junction by interacting with the interfacial tetrad. DOXO was found to be the best Q-D junction binder. Interestingly, the removal of the aminoglycosyl group significantly changed the pattern of the interactions, indicating that highly polar substituents have a stronger affinity with the exposed regions of the Q-D junction, particularly at the level of the interfacial tetrad.

摘要

四链体-双链（Q-D）接头是具有独特结构的基序，由于它们在基因组序列中频繁出现，因此作为药物靶点引起了越来越多的关注。选择病毒 HIV LTR-III 序列作为 Q-D 接头模型，研究所选化合物 BMH-21、纳米替康（ST-1968）和多柔比星（DOXO）的亲和力，所有这些化合物都含有一个平面多环芳烃部分，分别连接到一个短的氨基烷基或氨基糖基上。采用了一种结合了 NMR 光谱学、分子建模、圆二色性（CD）和荧光光谱学的多学科方法。研究的配体通过与界面四联体相互作用，对 Q-D 接头产生了适度但明显的稳定作用。发现 DOXO 是最好的 Q-D 接头结合物。有趣的是，氨基糖基的去除显著改变了相互作用的模式，表明高极性取代基与 Q-D 接头的暴露区域具有更强的亲和力，特别是在界面四联体的水平上。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/13a743d9b3a7/pone.0306239.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/8fd15f254031/pone.0306239.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/f617d2183dee/pone.0306239.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/99f7fbc84849/pone.0306239.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/58cc9289df4e/pone.0306239.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/5cb84882aba0/pone.0306239.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/740f353ab856/pone.0306239.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/13a743d9b3a7/pone.0306239.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/8fd15f254031/pone.0306239.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/f617d2183dee/pone.0306239.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/99f7fbc84849/pone.0306239.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/58cc9289df4e/pone.0306239.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/5cb84882aba0/pone.0306239.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/740f353ab856/pone.0306239.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda0/11268700/13a743d9b3a7/pone.0306239.g007.jpg

相似文献

1
Quadruplex-duplex junction in LTR-III: A molecular insight into the complexes with BMH-21, namitecan and doxorubicin.LTR-III 中的四重态-二联体连接：对与 BMH-21、奈拉滨和阿霉素复合物的分子洞察。
PLoS One. 2024 Jul 24;19(7):e0306239. doi: 10.1371/journal.pone.0306239. eCollection 2024.
2
De Novo Design of Selective Quadruplex-Duplex Junction Ligands and Structural Characterisation of Their Binding Mode: Targeting the G4 Hot-Spot.从头设计选择性四链体-双链连接配体及其结合模式的结构特征：靶向 G4 热点。
Chemistry. 2021 Apr 7;27(20):6204-6212. doi: 10.1002/chem.202005026. Epub 2021 Jan 22.
3
High-affinity binding at quadruplex-duplex junctions: rather the rule than the exception.四链体-双链体连接的高亲和力结合：是规则而不是例外。
Nucleic Acids Res. 2022 Nov 11;50(20):11948-11964. doi: 10.1093/nar/gkac1088.
4
Quadruplex-Duplex Junction: A High-Affinity Binding Site for Indoloquinoline Ligands.四重-双链连接：吲咯喹啉配体的高亲和结合位点。
Chemistry. 2020 Dec 15;26(70):16910-16922. doi: 10.1002/chem.202003540. Epub 2020 Nov 16.
5
Duplex formation in a G-quadruplex bulge.发夹结构在 G-四链体凸起处的形成。
Nucleic Acids Res. 2020 Oct 9;48(18):10567-10575. doi: 10.1093/nar/gkaa738.
6
Probing GFP Chromophore Analogs as Anti-HIV Agents Targeting LTR-III G-Quadruplex.探针对 HIV 药物靶点 LTR-III G-四链体的 GFP 生色团类似物的研究。
Biomolecules. 2021 Sep 26;11(10):1409. doi: 10.3390/biom11101409.
7
Nemorubicin and doxorubicin bind the G-quadruplex sequences of the human telomeres and of the c-MYC promoter element Pu22.奈莫柔比星和多柔比星与人端粒的G-四链体序列以及c-MYC启动子元件Pu22结合。
Biochim Biophys Acta. 2016 Jun;1860(6):1129-38. doi: 10.1016/j.bbagen.2016.02.011. Epub 2016 Feb 23.
8
Phenanthroline-bis-oxazole ligands for binding and stabilization of G-quadruplexes.菲咯啉-双-恶唑配体用于结合和稳定 G-四链体。
Biochim Biophys Acta Gen Subj. 2017 May;1861(5 Pt B):1281-1292. doi: 10.1016/j.bbagen.2016.11.024. Epub 2016 Nov 17.
9
Diarylethynyl amides that recognize the parallel conformation of genomic promoter DNA G-quadruplexes.能够识别基因组启动子DNA G-四链体平行构象的二芳基乙炔酰胺。
J Am Chem Soc. 2008 Nov 26;130(47):15950-6. doi: 10.1021/ja8046552.
10
Major G-Quadruplex Form of HIV-1 LTR Reveals a (3 + 1) Folding Topology Containing a Stem-Loop.HIV-1长末端重复序列的主要G-四链体形式揭示了一种包含茎环的(3 + 1)折叠拓扑结构。
J Am Chem Soc. 2018 Oct 24;140(42):13654-13662. doi: 10.1021/jacs.8b05332. Epub 2018 Oct 9.

引用本文的文献

1
Bridged Azobenzene Exhibits Fully Reversible Photocontrolled Binding to a G‑Quadruplex DNA/Duplex Junction.桥连偶氮苯对G-四链体DNA/双链体连接体表现出完全可逆的光控结合。
JACS Au. 2025 Aug 7;5(8):3846-3857. doi: 10.1021/jacsau.5c00532. eCollection 2025 Aug 25.
2
CUT&Tag reveals unconventional G-quadruplex landscape in Mycobacterium tuberculosis in response to oxidative stress.CUT&Tag技术揭示了结核分枝杆菌在应对氧化应激时非常规的G-四链体景观。
Nat Commun. 2025 Aug 6;16(1):7253. doi: 10.1038/s41467-025-62485-4.

本文引用的文献

1
High-affinity binding at quadruplex-duplex junctions: rather the rule than the exception.四链体-双链体连接的高亲和力结合：是规则而不是例外。
Nucleic Acids Res. 2022 Nov 11;50(20):11948-11964. doi: 10.1093/nar/gkac1088.
2
Indoloquinoline Ligands Favor Intercalation at Quadruplex-Duplex Interfaces.吲哚喹啉配体有利于在四链体-双链体界面处嵌入。
Chemistry. 2022 Feb 1;28(7):e202103718. doi: 10.1002/chem.202103718. Epub 2022 Jan 5.
3
G-Quadruplexes and Their Ligands: Biophysical Methods to Unravel G-Quadruplex/Ligand Interactions.
G-四链体及其配体：解析G-四链体/配体相互作用的生物物理方法
Pharmaceuticals (Basel). 2021 Aug 5;14(8):769. doi: 10.3390/ph14080769.
4
G-quadruplex binding properties of a potent PARP-1 inhibitor derived from 7-azaindole-1-carboxamide.一种源自 7-氮杂吲哚-1-甲酰胺的强效 PARP-1 抑制剂的 G-四链体结合特性。
Sci Rep. 2021 Feb 16;11(1):3869. doi: 10.1038/s41598-021-83474-9.
5
De Novo Design of Selective Quadruplex-Duplex Junction Ligands and Structural Characterisation of Their Binding Mode: Targeting the G4 Hot-Spot.从头设计选择性四链体-双链连接配体及其结合模式的结构特征：靶向 G4 热点。
Chemistry. 2021 Apr 7;27(20):6204-6212. doi: 10.1002/chem.202005026. Epub 2021 Jan 22.
6
Quadruplex-Duplex Junction: A High-Affinity Binding Site for Indoloquinoline Ligands.四重-双链连接：吲咯喹啉配体的高亲和结合位点。
Chemistry. 2020 Dec 15;26(70):16910-16922. doi: 10.1002/chem.202003540. Epub 2020 Nov 16.
7
Doxorubicin exhibits strong and selective association with VEGF Pu G-quadruplex.多柔比星与 VEGF Pu G-四链体具有强的和选择性的结合。
Biochim Biophys Acta Gen Subj. 2020 Dec;1864(12):129720. doi: 10.1016/j.bbagen.2020.129720. Epub 2020 Aug 27.
8
Selective targeting of mutually exclusive DNA G-quadruplexes: HIV-1 LTR as paradigmatic model.选择性靶向相互排斥的 DNA G-四链体：HIV-1 LTR 作为典范模型。
Nucleic Acids Res. 2020 May 21;48(9):4627-4642. doi: 10.1093/nar/gkaa186.
9
Stabilization of c-KIT G-Quadruplex DNA Structures by the RNA Polymerase I Inhibitors BMH-21 and BA-41.RNA 聚合酶 I 抑制剂 BMH-21 和 BA-41 稳定 c-KIT G-四链体 DNA 结构。
Int J Mol Sci. 2019 Oct 4;20(19):4927. doi: 10.3390/ijms20194927.
10
Major G-Quadruplex Form of HIV-1 LTR Reveals a (3 + 1) Folding Topology Containing a Stem-Loop.HIV-1长末端重复序列的主要G-四链体形式揭示了一种包含茎环的(3 + 1)折叠拓扑结构。
J Am Chem Soc. 2018 Oct 24;140(42):13654-13662. doi: 10.1021/jacs.8b05332. Epub 2018 Oct 9.