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A Density Functional Theory Study on the Kinetics and Thermodynamics of N-Glycosidic Bond Cleavage in 5-Substituted 2'- Deoxycytidines.
- Source :
-
Biochemistry . 8/14/2012, Vol. 51 Issue 32, p6458-6462. 5p. - Publication Year :
- 2012
-
Abstract
- B3LYP/6-311+G(2d,p)//B3LYP/6-31+G(d) density functional theory calculations were employed to explore the kinetics and thermodynamics of gas-phase N-glycosidic bond cleavage induced by nucleophilic attack of C1' with a hydroxide ion in 5-substituted 2'-deoxycytidines. The results showed that, among the 5-substituted 2'-deoxycytidine derivatives examined [XdC, where X = H (dC), CH3 (medC), CH2OH (hmdC), CHO (fmdC), COOH (cadC), F (FdC), or Br (BrdC)], fmdC and cadC exhibited the lowest energy barrier and largest exothermicity for N-glycosidic bond cleavage. These results paralleled previously reported nucleobase excision activities of human thymine DNA glycosylase (hTDG) toward duplex DNA substrates harboring a thymine and 5-substituted cytosine derivatives when paired with a guanine. Our study suggests that the inherent chemistry associated with the nucleophilic cleavage of N-glycosidic bond constitutes a major factor contributing to the selectivity of hTDG toward 5-substituted dC derivatives. These findings provided novel insights into the role of TDG in active cytosine demethylation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00062960
- Volume :
- 51
- Issue :
- 32
- Database :
- Academic Search Index
- Journal :
- Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 86149554
- Full Text :
- https://doi.org/10.1021/bi300797q