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用于平行 G-四链体的荧光猝灭配体。

Fluorescence Turn-Off Ligand for Parallel G-Quadruplexes.

机构信息

Department of Bioanalytical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland.

Laboratory of Molecular Assays and Imaging, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.

出版信息

Molecules. 2024 Aug 18;29(16):3907. doi: 10.3390/molecules29163907.

DOI:10.3390/molecules29163907
PMID:39202986
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11357100/
Abstract

Parallel-stranded G-quadruplex structures are found to be common in the human promoter sequences. We tested highly fluorescent 9-methoxyluminarine ligand (9-MeLM) binding interactions with different parallel G-quadruplexes DNA by spectroscopic methods such as fluorescence and circular dichroism (CD) titration as well as UV melting profiles. The results showed that the studied 9-MeLM ligand interacted with the intramolecular parallel G-quadruplexes (G4s) with similar affinity. The binding constants of 9-methoxyluminarine with different parallel G4s were determined. The studies upon oligonucleotides with different flanking sequences on c- G-quadruplex suggest that 9-methoxyluminarine may preferentially interact with 3'end of the c- promoter. The high decrease in 9-MeLM ligand fluorescence upon binding to all tested G4s indicates that 9-methoxyluminarine molecule can be used as a selective fluorescence turn-off probe for parallel G-quadruplexes.

摘要

平行股 G-四链体结构在人类启动子序列中很常见。我们通过荧光和圆二色性(CD)滴定以及紫外熔融曲线等光谱方法测试了高荧光 9-甲氧基呫吨(9-MeLM)配体与不同平行 G-四链体 DNA 的结合相互作用。结果表明,研究的 9-MeLM 配体与分子内平行 G-四链体(G4s)具有相似的亲和力。确定了 9-甲氧基呫吨与不同平行 G4 的结合常数。对具有不同侧翼序列的寡核苷酸的研究表明,9-甲氧基呫吨可能优先与 c-启动子的 3'端相互作用。结合所有测试的 G4 后,9-MeLM 配体荧光的高降低表明 9-甲氧基呫吨分子可以用作平行 G-四链体的选择性荧光关闭探针。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcbd/11357100/f0633a241efe/molecules-29-03907-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcbd/11357100/fd33683c326c/molecules-29-03907-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcbd/11357100/a71cdb4246ea/molecules-29-03907-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcbd/11357100/4b1dec6b0320/molecules-29-03907-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcbd/11357100/415fc101e061/molecules-29-03907-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcbd/11357100/f0633a241efe/molecules-29-03907-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcbd/11357100/fd33683c326c/molecules-29-03907-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcbd/11357100/a71cdb4246ea/molecules-29-03907-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcbd/11357100/4b1dec6b0320/molecules-29-03907-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcbd/11357100/415fc101e061/molecules-29-03907-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcbd/11357100/f0633a241efe/molecules-29-03907-g005.jpg

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本文引用的文献

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Molecules. 2022 Jun 29;27(13):4165. doi: 10.3390/molecules27134165.
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Role and significance of c-KIT receptor tyrosine kinase in cancer: A review.c-KIT 受体酪氨酸激酶在癌症中的作用和意义:综述。
Bosn J Basic Med Sci. 2022 Sep 16;22(5):683-698. doi: 10.17305/bjbms.2021.7399.
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G4LDB 2.2: a database for discovering and studying G-quadruplex and i-Motif ligands.
G4LDB 2.2:一个用于发现和研究 G-四链体和 i-Motif 配体的数据库。
Nucleic Acids Res. 2022 Jan 7;50(D1):D150-D160. doi: 10.1093/nar/gkab952.
4
Interaction of 9-Methoxyluminarine with Different G-Quadruplex Topologies: Fluorescence and Circular Dichroism Studies.9-甲氧基喜树碱与不同 G-四链体拓扑结构的相互作用:荧光和圆二色性研究。
Int J Mol Sci. 2021 Sep 27;22(19):10399. doi: 10.3390/ijms221910399.
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A Minimalistic Coumarin Turn-On Probe for Selective Recognition of Parallel G-Quadruplex DNA Structures.一种简约香豆素型荧光探针,用于选择性识别平行 G-四链体 DNA 结构。
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On the Road to Fight Cancer: The Potential of G-quadruplex Ligands as Novel Therapeutic Agents.在抗癌之路上:G-四链体配体作为新型治疗剂的潜力。
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G-quadruplexes: a promising target for cancer therapy.四链体:癌症治疗的有前景靶点。
Mol Cancer. 2021 Feb 25;20(1):40. doi: 10.1186/s12943-021-01328-4.
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Loop-mediated fluorescent probes for selective discrimination of parallel and antiparallel G-Quadruplexes.用于选择性区分平行和反平行 G-四链体的环介导荧光探针。
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