Mismatch Base Pairing of the Mutagen 8-Oxoguanine and Its Derivatives with Adenine:A Theoretical Search for Possible Antimutagenic Agents

摘要

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.