Citation: Cai Honglian, Zhou Cuisong, Yang Qiufang, Ai Tingting, Huang Yuqin, Lv You, Geng Jia, Xiao Dan. Single-molecule investigation of human telomeric G-quadruplex interactions with Thioflavin T[J]. Chinese Chemical Letters, ;2018, 29(3): 531-534. doi: 10.1016/j.cclet.2017.09.010 shu

Single-molecule investigation of human telomeric G-quadruplex interactions with Thioflavin T

Cai Honglian ^a ,
Zhou Cuisong ^a,, ,
Yang Qiufang ^a ,
Ai Tingting ^a ,
Huang Yuqin ^a ,
Lv You ^a ,
Geng Jia ^b ,
Xiao Dan ^a,,

a.
College of Chemistry, Sichuan University, Chengdu 610064, China
b.
Department of Laboratory Medicine, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China

Corresponding author: Zhou Cuisong, zcs@scu.edu.cn Xiao Dan, xiaodan@scu.edu.cn
Received Date: 29 June 2017
Revised Date: 14 August 2017
Accepted Date: 4 September 2017
Available Online: 6 March 2017

Figures(4)

G-quadruplex ligands have been accepted as potential therapeutic agents for anticancer treatment. Thioflavin T (ThT), a highly selective G-quadruplex ligand, can bind G-quadruplex with a fluorescent light-up signal change and high specificity against DNA duplex. However, there are still different opinions that ThT induces/stabilizes G-quadruplex foldings/topologies in human telomere sequence. Here, a sensitive single-molecule nanopore technology was utilized to analyze the interactions between human telomeric DNA (Tel DNA) and ThT. Both translocation time and current blockade were measured to investigate the translocation behaviors. Furthermore, the effects of metal ion (K⁺ and Na⁺) and pH on the translocation behaviors were studied. Based on the single-molecule level analysis, there are some conclusions:(1) In the electrolyte solution containing 50 mmol/L KCl and 450 mmol/L NaCl, ThT can bind strongly with Tel DNA but nearly does not change the G-quadruplex form; (2) In the presence of high concentration K⁺, the ThT binding induces the structural change of hybrid G-quadruplex into antiparallel topology with an enhanced structural stability; (3) In either alkaline or acidic buffer, G-quadruplex form will change in certain degree. All above conclusions are helpful to deeply understand the interaction behaviors between Tel DNA and ThT. This nanopore platform, investigating G-quadruplex ligands at the single-molecule level, has great potential for the design of new drugs and sensors.
- α-Hemolysin nanopore,
- Interaction,
- Human telomere sequence,
- Thioflavin T,
- G-Quadruplex ligand
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