Jiangsu Key Laboratory of New Power Batteries, Jiangsu Key Laboratory of Biofunctional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210097, China.
Molecules. 2012 Nov 28;17(12):14159-73. doi: 10.3390/molecules171214159.
Pyrene derivatives can be carcinogenic, teratogenic and mutagenic, thus having the potential to cause malignant diseases. In this work, the interactions of two selected pyrene derivatives (1-OHP and 1-PBO) and human tumor-related DNA (p53 DNA and C-myc DNA) are investigated by spectroscopic and non-native polyacrylamide gel electrophoresis (PAGE) methods. Using fluorescence spectrometry and circular dichroism (CD), DNA interactions of pyrene derivatives are confirmed to occur mainly via the groove binding mode supported by the intercalation into the base pairs of DNA. There is an obvious binding order of pyrene derivatives to the targeted DNA, 1-OHP > 1-PBO. The binding constants of 1-OHP are 1.16 × 10(6) L × mol(-1) and 4.04 × 10(5) L × mol(-1) for p53 DNA and C-myc DNA, respectively, while that of 1-PBO are only 2.04 × 10(3) L × mol(-1) and 1.39 × 10(3) L × mol(-1) for p53 DNA and C-myc DNA, respectively. Besides, the binding of pyrene derivatives to p53 DNA is stronger than that for C-myc DNA. CD and PAGE results indicate that the binding of pyrene derivatives can affect the helical structures of DNA and further induce the formation of double-chain antiparallel G-quadruplex DNA of hybrid G-rich sequences.
芘衍生物具有致癌性、致畸性和致突变性，因此有可能导致恶性疾病。在这项工作中，通过光谱和非天然聚丙烯酰胺凝胶电泳（PAGE）方法研究了两种选定的芘衍生物（1-OHP 和 1-PBO）与人肿瘤相关 DNA（p53 DNA 和 C-myc DNA）的相互作用。荧光光谱和圆二色性（CD）证实，芘衍生物与 DNA 的相互作用主要通过沟槽结合模式发生，该模式得到了 DNA 碱基对中嵌入的支持。芘衍生物与靶向 DNA 的结合顺序明显，1-OHP>1-PBO。1-OHP 与 p53 DNA 和 C-myc DNA 的结合常数分别为 1.16×10^6 L×mol^(-1)和 4.04×10^5 L×mol^(-1)，而 1-PBO 与 p53 DNA 和 C-myc DNA 的结合常数仅分别为 2.04×10^3 L×mol^(-1)和 1.39×10^3 L×mol^(-1)。此外，芘衍生物与 p53 DNA 的结合比与 C-myc DNA 的结合更强。CD 和 PAGE 结果表明，芘衍生物的结合可以影响 DNA 的螺旋结构，并进一步诱导杂交 G-富含序列的双链反平行 G-四链体 DNA 的形成。
