1887

Abstract

SUMMARY

Several triphosphates (TP) of 5-substituted deoxyuridine (dU), like 5-ethyl (Et), 5-n-propyl (n-Pr), 5-iso-propyl (iso-Pr), 5-n-hexyl (n-Hx), and 5-trifluorothymidine (F-dT) were used as substrates for polymerase α and for two herpes simplex virus ()-coded polymerases isolated from HeLa cells infected with -1, strain C42 (wild-type), or its mutant resistant to phosphonoformate ( ). All polymerases were purified up to the DNA-cellulose column step and they showed comparable specific activities. The incorporation into DNA studied with all the alkyl analogues of dUTP is several times higher with the virus enzymes than with polymerase α. The polymerase of the mutant virus incorporates dUTP analogues to a lower extent than the wild-type polymerase. The two virus enzymes also differ in the and values for different substrates, indicating that the mutation to PFA has affected the structure of the virus DNA polymerase. Surprisingly, all three enzymes use F-dTTP as substrate for DNA synthesis to an equal but limited extent.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-62-1-29
1982-09-01
2024-11-04
Loading full text...

Full text loading...

/deliver/fulltext/jgv/62/1/JV0620010029.html?itemId=/content/journal/jgv/10.1099/0022-1317-62-1-29&mimeType=html&fmt=ahah

References

  1. Bilello J., Kühne J., Koch G., Gauri K. K. 1981 Alkyldeoxyuridine: transport, phosphorylation, incorporation and their biological effects. In Design of Inhibitors of Viral Functions pp. 111–121 Edited by Gauri K. K. New York & London: Academic Press;
    [Google Scholar]
  2. Bollum F. J. 1959; Thermal conversion of non-priming deoxyribonucleic acid to primer. Journal of Biological Chemistry 234:2733–2734
    [Google Scholar]
  3. Bollum F. J. 1975; Mammalian DNA polymerases. Progress in Nucleic Acids Research and Molecular Biology 15:109–145
    [Google Scholar]
  4. Cheng Y.-C., Hoffmann P. J., Ostrander M., Grill S., Caradonna S., Tsou J., Chen J. C., Gallagher M. R., Flanagan T. D. 1979; Properties of herpesvirus-specific thymidine kinase, DNA polymerase and DNase and their implication in the development of specific antiherpes agents. Advances in Ophthalmology 38:173–186
    [Google Scholar]
  5. Erikson B., ÖBerg B. 1979; Characteristics of herpesvirus mutants resistant to phosphonoformate and phosphonoacetate. Agents and Chemotherapy 15:758–762
    [Google Scholar]
  6. Gauri K. K. 1979; Anti-herpesvirus polychemotherapy. Advances in Ophthalmology 38:151–163
    [Google Scholar]
  7. Gauri K. K. (editor) 1981 HSV mutants and antiviral drugs. In Design of Inhibitors of Viral Functions pp. 171–178 New York & London: Academic Press;
    [Google Scholar]
  8. Gauri K. K., Malorny G. 1967; Chemotherapie der Herpes-Infektion. Mit neuen 5-Alkyluracildesoxy- ribosiden. Archives of Pharmacology and Experimental Pathology 257:21–22
    [Google Scholar]
  9. Gauri K. K., Walter R. D. 1973; Inhibition of deoxythymidine kinase activity by the virostatic 5-ethyl-2'-deoxyuridine. Chemotherapy 18:269–273
    [Google Scholar]
  10. Gauri K. K., Pflughaupt K. W., Müller R. 1969; Synthese und photochemische Eigenschaften von l'-(2'-Desoxy-β-D-ribofuranosyl)-(4-3H)-5-äthyluracil. Zeitschrift für Naturforschung 24 B:833–836
    [Google Scholar]
  11. Gauri K. K., Shif I., Wolford R. G. 1976; Failure of 5-ethyl-2-deoxyuridine to induce oncogenic RNA (ONCORNA) viruses in Fischer rat embryo cells and BALB/3T3 mouse cells. Biochemical Pharmacology 25:1809–1810
    [Google Scholar]
  12. Gauri K. K., Pressler K., Schenk K. D., Scheffler G., Rebling R. 1979; Antiviral activity of compounds modified from the imidazolidinone derivative impacarcinum. Advances in Ophthalmology 38:255–266
    [Google Scholar]
  13. Kaufmann H. E., Heidelberger C. 1964; Therapeutic antiviral action of 5-trifluoromethyl-2'-deoxyuridine in herpes simplex. Science 145:585–586
    [Google Scholar]
  14. Kaufmann H. E., Martola M. D., Dohlman C. 1962; Hostal use of 5-iodo-2'-deoxyuridine (IDU) in treatment of herpes simplex keratitis. Archives of Ophthalmology 68:235–239
    [Google Scholar]
  15. Keir H. M., Hay J., Morrison J. M., Subak-Sharpe H. 1966; Altered properties of deoxyribonucleic acid nucleotidyltransferase after infection of mammalian cells with herpes simplex virus. Nature, London 210:369–371
    [Google Scholar]
  16. Kit S. 1976; Thymidine kinase, DNA synthesis and cancer. Molecular and Cellular Biology 11:161–182
    [Google Scholar]
  17. Koch G., Kowalzick L., HennefrÜnd J., SchÄrli C., KÜHne J., Anders C., Gauri K. K. 1981 Selective alteration of membrane permeability in cells infected by herpes simplex virus. In Design of Inhibitors of Viral Functions pp. 99–109 Edited by Gauri K. K. New York & London: Academic Press;
    [Google Scholar]
  18. Litman R. M. 1968; A deoxyribonucleic acid polymerase from Micrococcus luteus isolated on deoxyribonucleic acid-cellulose. Journal of Biological Chemistry 243:6222–6233
    [Google Scholar]
  19. Moffatt J. G. 1964; Synthesis of nucleoside-5'-triphosphates. Canadian Journal of Chemistry 42:599–604
    [Google Scholar]
  20. Pedrali-Noy G., Weissbach A. 1977; HeLa cell DNA polymerases: the effect of cycloheximide in vivo and detection of a new form of DNA polymerase. Biochimica et biophysica acta 477:599–604
    [Google Scholar]
  21. Pedrali-Noy G., Spadari S., Miller-Faures A., Miller A. O. A., Kruppa J., Koch G. 1980; Synchronization of HeLa cell cultures by inhibition of DNA polymerase with aphidicolin. Nucleic Acids Research 8:377–387
    [Google Scholar]
  22. Sagi J., Nowak R., Zumundzka B., Szemzö A., ÖtvöS L. 1980; A study of substrate specificity of mammalian and bacterial DNA polymerases with 5-alkyl-2'-deoxyuridine 5' triphosphates. Biochimica et biophysica acta 606:196–201
    [Google Scholar]
  23. Schabel F. M. Jr 1968; The antiviral activity of 9-β-D-arabinofuranosyladenine (ara-A). Chemotherapy 13:321–338
    [Google Scholar]
  24. Spadari S., Weissbach A. 1974; HeLa cell R-deoxyribonucleic acid polymerases. Journal of Biological Chemistry 249:5809–5815
    [Google Scholar]
  25. Spadari S., Muller R., Weissbach A. 1974; The dissimilitude of the low and high molecular weight deoxyribonucleic acid-dependent deoxyribonucleic acid polymerases of HeLa cells. Journal of Biological Chemistry 249:2991–2992
    [Google Scholar]
  26. Walter R. D., Gauri K. K. 1975; 5-ethyl-2'-deoxyuridine-5'-monophosphate inhibition of the thymidylate synthetase from Escherichia coli. Biochemical Pharmacology 24:1025–1027
    [Google Scholar]
  27. Weissbach A. 1977; Eukaryotic DNA polymerases. Annual Review of Biochemistry 46:25–47
    [Google Scholar]
  28. Weissbach A., Hong S.-C. C., Aucker J., Muller R. 1973; Characterization of herpes simplex virus-induced deoxyribonucleic acid polymerase. Journal of Biological Chemistry 248:6270–6277
    [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-62-1-29
Loading
/content/journal/jgv/10.1099/0022-1317-62-1-29
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error