The interaction of a structural flexible small molecule with nucleic acid structures: Investigation of the origin of fluorescence signal discrimination in sensing and the utilization in live cell imaging
The interaction of a structural flexible small molecule with nucleic acid structures: Investigation of the origin of fluorescence signal discrimination in sensing and the utilization in live cell imaging
复制标题
结构柔性小分子与核酸结构的相互作用：传感中荧光信号辨别的起源及其在活细胞成像中的应用的研究
DOI：
10.1016/j.snb.2017.05.018
复制
发表时间：
2017-10-01
影响因子：
8.4
通讯作者：
Chow, Cheuk-Fai
中科院分区：
文献类型：
--
作者：
Sun, Ning;Wang, Cong;Chow, Cheuk-Fai
噻唑橙(TO)对大多数核酸进行染色，非特异性地发出强烈的荧光信号。为了解决TO在DNA三级结构中的分辨能力差的问题，设计了一种平面和可旋转的pi共轭小分子，用乙烯取代亚甲基桥，略微增加了其结构灵活性，同时保持了关键的共轭共面双环体系。本研究探讨了该分子与不同DNA结构结合时信号识别的来源，结果表明该分子在DNA G-四链体和其他DNA三级结构之间表现出良好的荧光信号识别能力。在一个典型的染色实验中，该分子与Pu27结合时诱导的荧光信号比与ssDNA和dsDNA结合时强30倍。分子模拟研究也支持双环体系之间的柔性乙烯桥是诱导对G-四链体选择性的关键因素。此外，还用多种技术考察了该分子的选择性、灵敏度和稳定性。并考察了该分子作为G-四链显像剂在人前列腺癌PC3细胞和小鼠成纤维细胞L929中的应用。在细胞核中强烈观察到的绿色荧光信号表明，该分子能够进入细胞核，然后与G-四链体结合。(C)2017爱思唯尔B.V.保留所有权利。
Thiazole orange (TO) stains most nucleic acids giving strong fluorescence signal non-specifically. To resolve the poor discriminating ability of TO among tertiary structures of DNAs, a planar and rotatable pi-conjugated small molecule designed by replacing the methylene bridge with an ethylene that slightly increases its structural flexibility, while maintain the crucial conjugated co-planar two-ring system. The study addressed the origin of signal discrimination for the molecule upon binding with different DNA structures and the results demonstrate that the molecule exhibits excellent fluorescence signal discrimination between the DNA G-quadruplexes and other DNA tertiary structures. In a typical staining assay, the molecule induced 30-fold greater fluorescence signal upon binding with Pu27 than that of ssDNA and dsDNA. Molecular modelling studies also support that the flexible ethylene bridge between the two-ring system is the crucial factor for inducing selectivity towards G-quadruplexes. Furthermore, the selectivity, sensitivity, and stability of the molecule were investigated with various techniques. The application of the molecule as a selective staining agent for imaging of G-quadruplex in human prostate cancer cells PC3 and mouse fibroblast L929 was also investigated. The strongly observed green fluorescence signal in the cell nucleus suggests that the molecule is able to enter into the nucleus and then binding with G-quadruplexes. (C) 2017 Elsevier B.V. All rights reserved.