Mechanistic clues to the mutagenicity of alkylated DNA bases: a theoretical study.
Experiment indicates that the N7-guanine site in DNA is not "promutagenic" (mutation-inducing) on alkylation, while the O6-guanine and O4-thymine sites are so. These differences in nucleic acid template activity are attributed to corresponding differences in acidity of the Watson-Crick hydrogen bonding protons. Mechanistic indicators for ease of Watson-Crick proton loss are calculated using molecular orbital theory for DNA bases alkylated at the N7-guanine, O6-guanine and O4-thymine sites. Their values point to a definite favouring of the proton loss for the O-alkylated bases compared to the N7-alkylguanines. This may suggest the possibility that, at biological pH, the O-alkylated bases deprotonate readily while the N7-alkylguanines do not, thus accounting for observed differences in promutagenicity and nucleic acid template activity.
Duncan
R H
RH
Department of Chemistry, Indian Institute of Technology, Madras.
Davies
G S
GS
D000478:Alkylation; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004583:Electrons; D006860:Hydrogen Bonding; D009154:Mutation; D011522:Protons; D011685:Purine Nucleotides / Q000378:metabolism; D011742:Pyrimidine Nucleotides / Q000378:metabolism
D011522:Protons; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D004247:DNA