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

Autor: Yurenko YP; CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno (Czech Republic). yevgen.yurenko@ceitec.muni.cz., Novotný J; CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno (Czech Republic)., Sklenář V; CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno (Czech Republic).; National Center for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno (Czech Republic).; Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno (Czech Republic)., Marek R; CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno (Czech Republic). radek.marek@ceitec.muni.cz.; National Center for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno (Czech Republic). radek.marek@ceitec.muni.cz.; Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, 62500 Brno (Czech Republic). radek.marek@ceitec.muni.cz.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2015 Dec 01; Vol. 21 (49), pp. 17933-43. Date of Electronic Publication: 2015 Oct 23.
DOI: 10.1002/chem.201502977
Abstrakt: 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'-β or 2'-α,β 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.
(© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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