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一种能够选择性识别 G-四链体 DNA 的吡嗪-咪唑鎓衍生物。

A pyrene-imidazolium derivative that selectively recognizes G-quadruplex DNA.

机构信息

Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Republic of Korea.

出版信息

Biomaterials. 2012 Mar;33(7):2282-8. doi: 10.1016/j.biomaterials.2011.11.073. Epub 2011 Dec 21.

DOI:10.1016/j.biomaterials.2011.11.073
PMID:22196901
Abstract

G-quadruplexes, formed of four stranded guanine bases stabilized by monovalent cations, serve important role in cancer cell growth and control gene expression in telomere. Since there are various types of quadruplex structures, rapid and simple screening methods with high selectivity, sensitivity and nontoxicity are required for understanding about the biological roles of quadruplex DNA as well as in designing therapeutics. Herein, we report a pyrene-imidazolium derivative, JY-1, which can with high selectivity recognize G-quadruplex using fluorescence and NMR spectroscopy. This is the first example based on the imidazolium derivative, which can detect the G-quadruplex directly to utilize the excimer/monomer emission change in pyrene fluorophore. The selectivity of strong binding to a specific sequence can allow for quadruplex sensing and the detection method presented here is very simple, using fluorescence and NMR study. Also, the groove binding characteristic of JY-1 to the G-quadruplex has a relatively low nonspecific toxicity and the structure-specific differences in fluorescent character between DNA duplex and G-quadruplex may offer more discovery and application in biological study.

摘要

G-四链体由单价阳离子稳定的四个链状鸟嘌呤碱基组成,在癌细胞生长和端粒中控制基因表达方面发挥着重要作用。由于存在多种类型的四链体结构,因此需要快速、简单、具有高选择性、灵敏度和非毒性的筛选方法,以便了解四链体 DNA 的生物学作用,并设计治疗方法。在此,我们报告了一种基于芘-咪唑衍生物 JY-1 的方法,该方法可以使用荧光和 NMR 光谱高选择性地识别 G-四链体。这是首例基于咪唑衍生物的方法,它可以直接检测 G-四链体,利用芘荧光团的激基/单体发射变化。与特定序列强结合的选择性允许四链体传感,并且这里呈现的检测方法非常简单,使用荧光和 NMR 研究。此外,JY-1 与 G-四链体的沟结合特性具有相对较低的非特异性毒性,并且 DNA 双链体和 G-四链体之间荧光特性的结构特异性差异可能为生物研究提供更多的发现和应用。

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