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Mismatch base pairing of the mutagen 8‐oxoguanine and its derivatives with adenine: A theoretical search for possible antimutagenic agents
Author(s) -
Singh A. K.,
Mishra P. C.
Publication year - 2004
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.20395
Subject(s) - chemistry , steric effects , stacking , hydrogen bond , molecule , base pair , stereochemistry , nucleobase , base (topology) , molecular structure of nucleic acids: a structure for deoxyribose nucleic acid , computational chemistry , crystallography , dna , organic chemistry , mathematical analysis , biochemistry , mathematics
Molecular geometries of 8‐oxoguanine (8OG), those of its substituted derivatives with the substitutions CH 2 , CF 2 , CO, CNH, O, and S in place of the N7H7 group, adenine (A), and the base pairs of 8OG and its substituted derivatives with adenine were optimized using the RHF/6‐31+G* and B3LYP/6‐31+G* methods in gas phase. All the molecules and their hydrogen‐bonded complexes were solvated in aqueous media employing the polarized continuum model (PCM) of the self‐consistent reaction field (SCRF) theory using the RHF/6‐31+G* and B3LYP/6‐31+G* methods. The optimized geometrical parameters of the 8OG‐A base pair at the RHF/6‐31+G* and B3LYP/6‐31+G* levels of theory agree satisfactorily with those of an oligonucleotide containing the base pair found from X‐ray crystallography. The pattern of hydrogen bonding in the CF 2 ‐ and O‐substituted 8OG‐A base pair is of Watson–Crick type and that in the unsubstituted and CH 2 ‐, CNH‐, and S‐substituted base pairs is of Hoogsteen type. In the CO‐substituted base pair, the hydrogen bonding pattern is of neither Watson–Crick nor Hoogsteen type. The CF 2 ‐substitution appears to introduce steric hindrance for stacking of DNA bases. On the basis of these results, it appears that among all the substituted 8OG molecules considered here, the O‐substituted derivative may be useful as an antimutagenic drug. It is, however, subject to experimental verification. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005