Ribonucleotide reductase as a site of inhibition of DNA synthesis by the dialdehyde derivatives of purine nucleosides

Abstract

The dialdehyde derivatives of the purine nucleosides, prepared by the periodate-oxidation of the parent nucleoside, inhibit nucleic acid synthesis in Ehrlich tumor cells in vitro. The derivatives were shown to be inhibitors of ribonucleotide reductase activity in cell-free extracts prepared from Ehrlich tumor cells. It was shown that there was excellent correlation between the inhibition of DNA synthesis and the conversion of cytidine to deoxycytidine nucleotides via the ribonucleotide reductase step in intact cells. There was not a corresponding correlation with fluorodeoxyuridine, methotrexate, cytosine arabinoside and actinomycin-D.