Substituting CF2 for O4' in Components of Nucleic Acids: Towards Systems with Reduced Propensity to Form Abasic Lesions

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Authors

YURENKO Yevgen NOVOTNÝ Jan SKLENÁŘ Vladimír MAREK Radek

Year of publication 2015
Type Article in Periodical
Magazine / Source Chemistry - A European Journal
MU Faculty or unit

Central European Institute of Technology

Citation
Web DOI: 10.1002/chem.201502977
Doi http://dx.doi.org/10.1002/chem.201502977
Field Physical chemistry and theoretical chemistry
Keywords density functional calculations; DNA; fluorinated compounds; G-quadruplexes; relaxed force constants
Attached files
Description Intrinsic structural features and energetics of nucleotides containing variously fluorinated sugars as potential building blocks of DNA duplexes and quadruplexes are explored systematically using the modern methods of density functional theory (DFT) and quantum chemical topology (QCT). Our results suggest that fluorination at the 2'-B or 2'-A,B positions somewhat stabilizes in vacuo the AI relative to the BI conformations. In contrast, substitution of the CF2 group for the O4' atom (O4'-CF2 modification) leads to a preference of the BI relative to AI DNA-like conformers. All the studied modifications result in a noticeable increase in the stability of the glycosidic bond [estimated by the relaxed force constants (RFC) approach], with particularly encouraging results for the O4'-CF2 derivative. Consequently, the O4'-CF2 modified systems are suggested and explored as promising scaffolds for the development of duplex and quadruplex structures with reduced propensity to form abasic lesions and to undergo DNA damage.
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