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近红外荧光配体的分子工程用于追踪线粒体 DNA G-四链体。

Molecular engineering of a near-infrared fluorescent ligand for tracking mitochondrial DNA G-quadruplexes.

机构信息

School of Pharmaceutical Sciences, Shenzhen University Health Science Center, Shenzhen, 518060, China; International Cancer Center, Shenzhen University Health Science Center, Shenzhen, 518060, China.

出版信息

Anal Chim Acta. 2021 Jul 18;1169:338600. doi: 10.1016/j.aca.2021.338600. Epub 2021 May 13.

DOI:10.1016/j.aca.2021.338600
PMID:34088367
Abstract

G-quadruplexes are supposed to exist in mitochondrial DNA, which may participate in the regulation of mitochondrial metabolism. However, their formation dynamics and cellular roles are still unknown, calling for the development of promising small-molecule fluorescent probes for detecting mitochondrial DNA (mtDNA) G4s in live cells. In this study, we engineered a NIR fluorescent probe termed IZIN-1 by conjugating a typical G4 ligand and a mitochondrion-targeting AIE luminogen, which was then found to be able to emit NIR fluorescence by binding to mtDNA G4s via a distinctive mode. Cell-based experiments demonstrated that IZIN-1 may track mtDNA G4 formation in live cells. Collectively, this work provides a promising example about how to design a fluorescent probe targeting mtDNA G4s, and also offers a feasible chemical tool for investigating mtDNA G4s in live cells.

摘要

四链体被认为存在于线粒体 DNA 中,可能参与线粒体代谢的调节。然而,它们的形成动力学和细胞作用仍然未知,这就需要开发有前途的小分子荧光探针来检测活细胞中的线粒体 DNA(mtDNA)G4。在本研究中,我们通过连接一个典型的 G4 配体和一个线粒体靶向的 AIE 发光体,设计了一个近红外荧光探针,命名为 IZIN-1,通过一种独特的模式与 mtDNA G4 结合,从而可以发出近红外荧光。基于细胞的实验表明,IZIN-1 可以在活细胞中追踪 mtDNA G4 的形成。总的来说,这项工作为设计靶向 mtDNA G4 的荧光探针提供了一个有前景的范例,也为研究活细胞中的 mtDNA G4 提供了一种可行的化学工具。

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A rapid investigation of near-infrared (NIR) fluorescent switch-on probes for detection and in cellulo tracking of G-quadruplex and double-stranded DNA.用于检测和细胞内追踪G-四链体及双链DNA的近红外(NIR)荧光开启型探针的快速研究。
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Enhanced mitochondrial G-quadruplex formation impedes replication fork progression leading to mtDNA loss in human cells.
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