The interactions between a small molecule and G-quadruplexes are visualized by fluorescence lifetime imaging microscopy

被引：185

作者：

Shivalingam, Arun ^{[1
]}

Izquierdo, M. Angeles ^{[1
]}

Le Marois, Alix ^{[2
]}

Vysniauskas, Aurimas ^{[1
]}

Suhling, Klaus ^{[2
]}

Kuimova, Marina K. ^{[1
]}

Vilar, Ramon ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Dept Chem, London SW7 2AZ, England

[2] Kings Coll London, Dept Phys, London WC2R 2LS, England

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

英国工程与自然科学研究理事会;

关键词：

PHOTOINDUCED ELECTRON-TRANSFER; AZATRIANGULENIUM SALTS; LIVING CELLS; DNA; TELOMERES; PROMOTER; BINDING; DUPLEX; PROBES;

D O I：

10.1038/ncomms9178

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Guanine-rich oligonucleotides can fold into quadruple-stranded helical structures known as G-quadruplexes. Mounting experimental evidence has gathered suggesting that these non-canonical nucleic acid structures form in vivo and play essential biological roles. However, to date, there are no small-molecule optical probes to image G-quadruplexes in live cells. Herein, we report the design and development of a small fluorescent molecule, which can be used as an optical probe for G-quadruplexes. We demonstrate that the fluorescence lifetime of this new probe changes considerably upon interaction with different nucleic acid topologies. Specifically, longer fluorescence lifetimes are observed in vitro for G-quadruplexes than for double-and single-stranded nucleic acids. Cellular studies confirm that this molecule is cell permeable, has low cytotoxicity and localizes primarily in the cell nucleus. Furthermore, using fluorescence lifetime imaging microscopy, live-cell imaging suggests that the probe can be used to study the interaction of small molecules with G-quadruplexes in vivo.

引用

页数：10

共 42 条

[1] Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? [J].