Nucleic acids and alkylating agents: Carbon-13 magnetic resonance studies of the methylation of ribonucleic acid with methyl methanesulfonate

Abstract

Direct examination of the interaction of ribonucleic acid with the alkylating agent, methyl methanesulfonate, by carbon-13 magnetic resonance spectroscopy has demonstrated the potential usefulness of this new spectroscopic method in studying the interaction between nucleic acids and biologically active agents. By comparison with the model compounds isolated from the reactions of mononucleotides with methyl methanesulfonate, five methylated products, 7-methylguanosine (49.7%), 1-methyladenosine (21.2%), 3-methyl cytosine (12.7%), 1-methylguanosine (7.5%), and methyl phosphate (8.9%, tentative) have been identified in the alkylated RNA from the reaction without buffer, whose pH is maintained using a pH stat; three methylated products, 7-methylguanosine (61.1%), 1-methyladenosine (20.5%), and 3-methylcytosine (18.4%) have been identified from the reaction in phosphate buffer. These quantitative differences may account for the failure of previous structure-activity correlations. The limits of the biological interpretation of the present and previous chemical results are discussed.