Reactions of β-propiolactone, β-butyrolactone and γ-butyrolactone with nucleic acids

Abstract Reactivity of β-propiolactone, β-butyrolactone and γ-butyrolactone with guanosine, RNA, DNA and 4-(p-nitrobenzyl)pyridine was studied. β-Propiolactone was 50–100 times more reactive with all the nucleophiles than β-butyrolactone whereas γ-butyrolactone was completely inactive. The rate of alkylation by the lactones was guanosine > RNA = denatured DNA > double-stranded DNA. The type of the adducts formed were characterized by fluorescence and ultraviolet spectroscopy. Similar alkylation products were formed by the two lactones. The main sites alkylated were N-1 at adenosine, N-3 at cytidine and N-7 at guanosine. The results suggest that the carcinogenic potency of the lactones correlates with their reactivity rather than with specificity of the adducts formed.