FURTHER STUDIES ON THE ALKYLATION OF NUCLEIC ACIDS AND THEIR CONSTITUENT NUCLEOTIDES

Publisher Website
Google Scholar
Abstract
Sites in the nucleic acids reactive towards alkylating agents are shown to be, in order of decreasing reactivity: for RNA, N-7 of guanine, N-1 of adenine, N-1 of cytosine and N-3 of adenine; for DNA, N-7 of guanine, N-3 of adenine, N-l of adenine and N-l of cytosine. Denatured DNA behaves in this respect like RNA. The observed differences between DNA and RNA are ascribed to the involvement of N-l of adenine and of cytosine in hydrogen-bond formation in DNA. In all cases alkylation results in destabilization of the nucleosides or the corresponding moieties inthe nucleic acids. At neutral pH, with DNA, 7-alkylguanines and 3-alkyladenines are slowly liberated by hydrolysis, the latter at the greater rate, whereas with RNA slow rearrangements occur, 1-alkyladenine moieties yielding 6-methylaminopurine moieties and 1-alkylcytosines giving the corresponding 1-alkyluracils. The influences of the nature of the 7-and 9-substituents on the rate of hydrolysis or ring-fission of 7,9-disubstituted guanines in the range of pH 5-10 was studied and their pK''a values were determined. Possible correlations between these reactions and the biological properties of the alkylating agents are discussed.