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

YURENKO, Yevgen, Jan NOVOTNÝ, Vladimír SKLENÁŘ and Radek MAREK. Substituting CF2 for O4' in Components of Nucleic Acids: Towards Systems with Reduced Propensity to Form Abasic Lesions. Chemistry - A European Journal. WEINHEIM: Wiley, 2015, vol. 21, No 49, p. 17933-17943. ISSN 0947-6539. Available from: https://dx.doi.org/10.1002/chem.201502977.

Basic information

• Original name: Substituting CF2 for O4' in Components of Nucleic Acids: Towards Systems with Reduced Propensity to Form Abasic Lesions
• Authors: YURENKO, Yevgen (804 Ukraine, belonging to the institution), Jan NOVOTNÝ (203 Czech Republic, belonging to the institution), Vladimír SKLENÁŘ (203 Czech Republic, belonging to the institution) and Radek MAREK (203 Czech Republic, guarantor, belonging to the institution).
• Edition: Chemistry - A European Journal, WEINHEIM, Wiley, 2015, 0947-6539.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10403 Physical chemistry
• Country of publisher: Germany
• Confidentiality degree: is not subject to a state or trade secret
• WWW: DOI: 10.1002/chem.201502977
• Impact factor: Impact factor: 5.771
• RIV identification code: RIV/00216224:14740/15:00084338
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1002/chem.201502977
• UT WoS: 000367185700049
• Keywords in English: density functional calculations; DNA; fluorinated compounds; G-quadruplexes; relaxed force constants
• Tags: rivok
• Tags: International impact, Reviewed

Abstract

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.

Links

• ED1.1.00/02.0068, research and development project: Name: CEITEC - central european institute of technology
• 286154, interní kód MU: Name: SYLICA - Synergies of Life and Material Sciences to Create a New Future (Acronym: SYLICA)

Investor: European Union, Capacities