Meso-α,β-diphenylsuccinate and Hydroxyurea as Inhibitors of Deoxycytidylate Synthesis in Extracts of Ehrlich Ascites and L Cells

Abstract

Abstract The formation of deoxycytidylate in soluble extracts of Ehrlich ascites cells grown in white Swiss mice and of L cells grown in monolayer cultures was shown to occur by ribonucleotide reduction without cleavage of the glycosidic bond. Meso-α,β-diphenylsuccinate, which had previously been described as a specific inhibitor for the activation of deoxyribose 5-phosphate aldolase, was found to block the nucleotide reductase reaction in these extracts. The inhibitory effectiveness was indistinguishable from that observed with hydroxyurea, and both agents affected the reduction reaction but not the kinases responsible for converting cytidine monophosphate to cytidine diphosphate and triphosphate.