5-MERCAPTODEOXYURIDINE - ITS ENZYMATIC SYNTHESIS AND MODE OF ACTION IN MICROBIOLOGICAL SYSTEMS

5-Mercapto-2′-deoxyuriCline (MUdR) was synthesized by enzymatic transfer of the deoxyribosyl group of thymidine (TdR) to 5-mercaptouracil (MU), by using the trans-N-deoxyribosylase from Lactobacillus helveticus. The acceptor and donor activities of MU, MUdR and their respective disulfides were studied in this enzyme system; the disulfides were found inactive as substrates, but they showed the same growth inhibitory activities as the corresponding thiols in the microbiological assays. MUdR was nearly as active as 5-fluoro-2′-deoxyuridine (FUdR) in the Lactobacillus leichmannii assay, but was considerably less active than FUdR in the Lactobacillus arabinosus and Streptococcus faecalis systems. Inhibition analysis studies indicated that MUdR, like FUdR, acts via inhibition of thymidylate synthetase. The significant differences found in the spectra of activities of MU and MUdR, as compared to those of 5-fluorouracil (FU) and FUdR, are related to differences in the routes and efficiency of their metabolic activation in which the mercapto analogs, due to the size of their 5-S- group, are restricted to the pathways available for the metabolic transformations of thymine and TdR, while the fluoro analogs may be converted to the nucleotide via the uracil pathway. Some synergism and cross-resistance studies are also reported. © 1969.