Isolation and identification of products from alkylation of nucleic acids: ethyl- and isopropyl purines

Article abstract of DOI:10.1042/bj1450073

Ethylation and isopropylation of guanine in alkaline solution, or of adenine in formic acid, by alkyl methanesulphonates gave the following products: 1, N², 3, O⁶, 7 and 9 alkylguanines; 1, 3, 7 and 9 alkyladenines. The products were identified from their characteristic UV absorption spectra, by comparison with either known ethyladenines or with the corresponding known methyladenines, and were also characterized by mass spectrometry. Their chromatographic properties on paper, TLC and various columns were determined. DNA was alkylated in neutral solution with ¹⁴C labelled alkyl methanesulphonates and the ratios of the alkylpurines formed were obtained, and compared for alkylation by methyl, ethyl and isopropyl methanesulphonates and by N methyl N nitrosourea. The extents of alkylation at O 6 of guanine relative to those at N 7 of guanine varied with the reactivity of the methylating agents according to the predictions of Swain & Scott relating nucleophilicity of the groups alkylated with the substrate constants of the alkylating agents. The relative extents of alkylation at N 3 of adenine did not allow this correlation.