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Published on: January 20, 2016
Studies on the interaction mechanism of pyrene derivatives with human tumor-related DNA
1Jiangsu Key Laboratory of New Power Batteries, Jiangsu Key Laboratory of Biofunctional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210097, China.
Abstract:
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.
Insights
Pyrene derivatives interact with tumor DNA, primarily through groove binding and intercalation. 1-OHP shows stronger binding than 1-PBO, potentially altering DNA structure and forming G-quadruplexes.
Area of Science:
- Environmental Chemistry
- Molecular Biology
- Biochemistry
Background:
- Pyrene derivatives are known carcinogens with mutagenic and teratogenic potential.
- Understanding their interaction with human tumor DNA is crucial for assessing health risks.
- Specific DNA targets include tumor suppressor genes like p53 and oncogenes like C-myc.
Purpose of the Study:
- To investigate the binding interactions between pyrene derivatives (1-OHP and 1-PBO) and human tumor-related DNA (p53 DNA and C-myc DNA).
- To elucidate the binding modes and affinities of these interactions.
- To assess the impact of these interactions on DNA structure.
Main Methods:
- Spectroscopic techniques, including fluorescence spectrometry and circular dichroism (CD).
- Non-native polyacrylamide gel electrophoresis (PAGE) for structural analysis.
- Quantitative analysis of binding constants.
Main Results:
- Pyrene derivatives bind to DNA via groove binding and intercalation.
- 1-OHP exhibits significantly stronger binding affinity to both p53 DNA and C-myc DNA compared to 1-PBO.
- Binding to p53 DNA is stronger than to C-myc DNA for both derivatives.
- DNA structural changes and induction of G-quadruplex formation were observed.
Conclusions:
- The binding affinity follows the order: 1-OHP > 1-PBO.
- Pyrene derivatives can alter DNA helical structures and induce G-quadruplex formation.
- These findings provide insights into the molecular mechanisms of pyrene derivative genotoxicity.
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