Chemical modification of deoxyribonucleic acids: a direct study by carbon-13 nuclear magnetic resonance spectroscopy

The chemical modifications of salmon sperm and salmon testes DNAs with 90% super(13)C-enriched methyl methanesulfonate have been directly studied by super(13)C NMR and super(31)P NMR. This direct stable isotope approach eliminates all tedious degradation and separation processes for determining the reactive sites and product distribution in studying the in vitro interaction between biological macromolecules and bioactive compounds. Seven methylated products, 7-methyleoxyguanosine, 1-methyldeoxyadenosine, 3-methyldeoxycytidine, 1-methyldeoxyguanosine, 3-methylthymidine, methyl phosphodiester, and methyl phosphotriester were determined by comparison with model compounds and extensive study of the chemical properties of the methylated DNA. The relative specificity of the methylation reactions may correlate with the DNA conformation.