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摘要
Reactions of a hydroxyl radical with nucleotides may lead to DNA damage formation. In this study the emphasis was placed on the double helix structure deformation, forced by 5';R and 5';S diastereomers of 5';,8-cyclo-2';-deoxyadenosine (cdA). It should be pointed out that (5';R)cdA and (5';S)cdA are formed in cells with different frequencies. Moreover both diastereomers showed different biological/biochemical behaviours. The results of theoretical QM/MM studies, presented in this article, show the slight influence of (5';S)cdA on the spatial geometry of ds-DNA opposite to (5';R)cdA. The structure of the double helix containing (5';R)cdA adopted the three dimensional shape similar to the 3D structure of ds-DNA containing cisplatin. Probably due to this fact, (5';R)cdA was found as a better substrate for NER system than (5';S)cdA. w3DNA analyses revealed that the 5';R diastereomer left the ds-DNA in natural B form instead of 5';S, which disrupted the internal parameters of the double helix in both directions. Probably, due to this, (5';R)cdA was not found as an inhibitor of polymerase-η activity opposite to (5';S)cdA, which was recognised as a stop point of the DNA elongation process. Therefore, the presented results are in good agreement with previous experimental data. Additionally, the strength of individual hydrogen bonds formed by 5';R and 5';S 5';,8-cyclo-2';-deoxyadenosines in ds-DNA structures, vertical electron affinity and vertical ionisation potential as well as stacking interaction were taken into consideration.
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