Selective visualization of DNA G-quadruplex structures in live cells with 1-methylquinolinium-based molecular probes: The importance of indolyl moiety position towards specificity
Selective visualization of DNA G-quadruplex structures in live cells with 1-methylquinolinium-based molecular probes: The importance of indolyl moiety position towards specificity
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使用基于 1-甲基喹啉鎓的分子探针选择性可视化活细胞中的 DNA G 四链体结构：吲哚基部分位置对特异性的重要性
DOI：
10.1016/j.dyepig.2017.04.038
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发表时间：
2017-08
影响因子：
4.5
通讯作者：
Wong WL
中科院分区：
文献类型：
--
作者：
Lu Yu-Jing;Guo Xiao-Lu;Xu Miao-Han;Chen Wei-Wu;Zhang Kun;Zhang Kun;Wong Wing-Leung;Wong Wing-Leung;Chow Cheuk-Fai;Lu YJ;Zhang K;Wong WL
通过与吲哚基的结构包合，开发了一类基于 1-甲基喹啉的小分子荧光探针，在活细胞 DNA G 四链体结构成像中具有高特异性。研究表明，1-甲基喹啉鎓和吲哚环的支架是新型探针分子设计的独特组合，具有有效且灵敏的荧光信号开启功能，特别是用于识别端粒DNA、识别启动子中的G-四链体以及对来自其他DNA结构的DNA G-四链体进行成像或可视化。此外，实验结果表明，在分子探针设计和合成中，吲哚基部分及其通过亚乙基桥与 1-甲基喹啉鎓支架结合时的重要性是一个很少被研究的因素；这些因素被确定为导致在活人前列腺癌细胞（PC-3细胞）实验中 DNA G 四链体与其他核酸特异性区分的优异荧光信号开启特性的关键根源。通过荧光滴定、非变性 PAGE 实验和 CD 分析对新探针的特性进行了全面研究，以验证与 DNA G 四链体结构相互作用时的选择性、灵敏度和稳定性。
A class of small 1-methylquinolinium-based molecular fluorescent probes with high specificity in DNA G-quadruplex structures imaging in live cells was developed through the structural inclusion with an indolyl moiety. The study reveals that the scaffold of 1-methylquinolinium and indole ring is a distinctive combination for molecular design of new probes with effective and sensitive fluorescent signal switch-on functionality, particularly for identifying telomeric DNA, recognizing G-quadruplexes in promoters, and imaging or visualization of DNA G-quadruplex from other DNA structures. In addition, the experimental results demonstrate a rarely investigated factor on the importance of the indolyl moiety and its position when conjugating with a 1-methylquinolinium scaffold though a ethylene bridge in molecular probe design and synthesis; and these factors are determined as the crucial root leading to the excellent fluorescent signal switch-on property for the specific discrimination of DNA G-quadruplexes against other nucleic acids in live human prostate cancer cells (PC-3 cells) experiments. The characteristics of the new probes were comprehensively investigated with fluorescence titration, native PAGE experiments, and CD analysis to validate the selectivity, sensitivity, and stability while interacting with DNA G-quadruplex structures.
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