Synthese und photochemische Eigenschaften von l′-(2′-Desoxy-β-D-ribofuranosyl)-(4-³H)-5-äthyluracil

Abstract

Chemical synthesis of C-4 tritium labeled 1′-(2′-deoxy-β-ᴅ-ribofuranosyl) -5-ethyluracil, also named as 5-ethyl-2′-deoxyuridine, a virostatic compound of therapeutic value, is described. The β-configuration has been derived from its optical rotatory dispersion spectrum, NMR spectrum and from its enzymatic hydrolysis.Incorporation of 5-ethyluracil into DNA of phages, bacteria and of mammalian cells has been already demonstrated. To follow the photochemical behavior of 5-ethyluracil in DNA, valid information in vitro can be expected from experiments with the 5-ethyl-2′-deoxyuridine alone; because we have already shown that contrary to 5-ethyl-, 5-propyl- and 5-butyluracil their N-1 and/or N-3 substituted mono and/or di-alkyl derivatives undergo photodimerisation. Similarly, as expected 5-ethyl-2′-deoxyuridine dimerises upon U.V.-Irradiation also (48%). Under the same experimental conditions thymidine dimerises practically to same extent as well (49%). From these results in vitro it follows that replacement of thymidine with 5-ethyluracil into DNA should not essentially alter its normal behavior towards U.V.-light.

Differential Incorporation of Thymidylate Analogues into DNA by DNA Polymerase and by DNA Polymerases Specified by Two Herpes Simplex Viruses

“…The detail of the synthesis of 5-alkyl deoxyuridines and their corresponding monophosphates has been described previously (Gauri et al, 1969;Walter & Gauri, 1975). Triphosphates were synthesized according to the method of Walter & Gauri (1975) and Moffatt (1964).…”

Antiviral activity of 5-ethyl-2'-deoxyuridine against herpes simplex viruses in cell culture, mice, and guinea pigs

“…Antiviral properties of EdU are probably mediated by the HSV-encoded TK. After selective phosphorylation of the drug by the viral TK and further phosphorylation by cellular enzymes, EdU-5'-triphosphate may incorporate into virus DNA as counterfeit thymidine, although the evidence for this is not conclusive (19,26). To confirm the role of the viral TK in activating this drug, EdU-resistant HSV variants were prepared in cell culture.…”

Induction and inhibition of Friend erythroleukemia cell differentiation by pyrimidine analogs: analysis of the requirement for intracellular accumulation and incorporation into DNA.

“…This series of alkyldeoxyuridines has been synthesized for potential use in antiherpesvirus chemotherapy (8,9). They differ from thymidine in that the 5-methyl group is replaced by larger straight-chain or branched alkyl groups of two to six carbon atoms.…”

“…Originally the B8 and B8/7 cell lines were selected for their ability to grow in high concentrations (150 ,Lg/ml) of BrdU, and both were shown to be TK-. B8 has partially reverted, has a low level of TK activity, and is sensitive to growth in 20 ,ug of BrdU per ml (17, 22; unpublished data at 37°C in the presence of radiolabeled nucleosides which were prepared as described (9). An identical number of counts (107) was present in each assay, and unlabeled thymidine or BrdU was added to account for differences in specific activity.…”