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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Interaction of adenine adducts with thymine: a computational study
Prabhat K Sahu1, Chang-Wang Kuo, Shyi-Long Lee
1Department of Chemistry and Biochemistry, National Chung Cheng University, Chia-Yi, 621 Taiwan.
The Journal of Physical Chemistry. B
|March 29, 2007
Summary
DNA adducts like 1,N6-ethenoadenine (epsilonA) and 1,N6-ethanoadenine (EA) can cause cancer by mispairing with thymine. This study reveals EA(2)-T(I) and EA(1)-T(II) exhibit stronger interactions with thymine than the standard A-T base pair.
Area of Science:
- Computational Chemistry
- Molecular Biology
- Toxicology
Background:
- DNA adducts, such as 1,N6-ethenoadenine (epsilonA) and 1,N6-ethanoadenine (EA), pose a risk of carcinogenesis due to potential mispairing with DNA bases.
- Understanding the molecular interactions of these adducts with thymine is crucial for assessing DNA damage.
Purpose of the Study:
- To investigate the molecular interactions between adenine adducts (epsilonA and EA) and thymine (T).
- To compare the structural, energetic, and hydrogen-bonding properties of these adducts with the Watson-Crick adenine-thymine (A-T) base pair.
Main Methods:
- Utilized computational methods, including B3LYP/6-31+G* for geometry optimization and MP2/6-311++G** for single-point energy calculations.
- Analyzed various stable conformers of epsilonA-T and EA-T complexes.
- Calculated basis set superposition error (BSSE)-corrected hydrogen-bonding strengths and reaction enthalpies.
Main Results:
- Identified multiple stable conformers for epsilonA-T and EA-T interactions.
- Determined that certain ethano adducts (EA) form stronger hydrogen bonds with thymine than the canonical A-T base pair, with EA(2)-T(I) showing the highest strength (15.30 kcal/mol).
- Calculated reaction enthalpies indicated that epsilonA(2)-T(I) and EA(1)-T(II) interactions are significantly stronger than the A-T base pair.
Conclusions:
- Adenine adducts, particularly ethano derivatives, can form more stable complexes with thymine compared to the natural A-T base pair.
- These findings provide fundamental insights into the molecular mechanisms underlying DNA damage caused by adenine adducts.
- The study aids in future experimental investigations into the genotoxic potential of these adducts.
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