Reactions of beta-propiolactone, beta-butyrolactone and gamma-butyrolactone with nucleic acids

Reactivity of beta-propiolactone, beta-butyrolactone and gamma-butyrolactone with guanosine, RNA, DNA and 4-(p-nitrobenzyl)pyridine was studied. beta-Propiolactone was 50--100 times more reactive with all the nucleophiles than beta-butyrolactone whereas gamma-butyrolactone was completely inactive. The rate of alkylation by the lactones was guanosine greater than RNA = denatured DNA greater than 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.