Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1984 Nov;26(5):778–780. doi: 10.1128/aac.26.5.778

Kinetics of the interaction of monophosphates of the antiviral nucleosides 2'-fluoro-1-beta-D-arabinofuranosylpyrimidine and (E)-5-(2-bromovinyl)-2'-deoxyuridine with thymidylate kinases from Vero cells and herpes simplex virus types 1 and 2.

M S Chen, L A Amico, D J Speelman
PMCID: PMC180014  PMID: 6083755

Abstract

The affinities of the monophosphates of 2'-fluoro-5-iodo-1-beta-D-arabinofuranosyluracil and its 5-methyl analog for cellular thymidylate kinase were two or more orders of magnitude greater than for the thymidine-thymidylate kinases from herpes simplex virus types 1 and 2. In contrast, the monophosphate of (E)-5-(2-bromovinyl)-2'-deoxyuridine was found to have a higher affinity for the viral enzymes than for the cellular enzyme.

Full text

PDF
778

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashton W. T., Karkas J. D., Field A. K., Tolman R. L. Activation by thymidine kinase and potent antiherpetic activity of 2'-nor-2'-deoxyguanosine (2'NDG). Biochem Biophys Res Commun. 1982 Oct 29;108(4):1716–1721. doi: 10.1016/s0006-291x(82)80109-5. [DOI] [PubMed] [Google Scholar]
  2. Chen M. S., Chang P. K., Prusoff W. H. Photochemical studies and ultraviolet sensitization of Escherichia coli thymidylate kinase by various halogenated substrate analogs. J Biol Chem. 1976 Nov 10;251(21):6555–6561. [PMC free article] [PubMed] [Google Scholar]
  3. Chen M. S., Prusoff W. H. Association of thymidylate kinase activity with pyrimidine deoxyribonucleoside kinase induced by herpes simplex virus. J Biol Chem. 1978 Mar 10;253(5):1325–1327. [PubMed] [Google Scholar]
  4. Chen M. S., Walker J., Prusoff W. H. Kinetic studies of herpes simplex virus type 1-encoded thymidine and thymidylate kinase, a multifunctional enzyme. J Biol Chem. 1979 Nov 10;254(21):10747–10753. [PubMed] [Google Scholar]
  5. Cheng Y. C., Dutschman G., Fox J. J., Watanabe K. A., Machida H. Differential activity of potential antiviral nucleoside analogs on herpes simplex virus-induced and human cellular thymidine kinases. Antimicrob Agents Chemother. 1981 Sep;20(3):420–423. doi: 10.1128/aac.20.3.420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cheng Y. C., Ostrander M. Deoxythymidine kinase induced in HeLa TK- cells by herpes simplex virus type I and type II. II. Purification and characterization. J Biol Chem. 1976 May 10;251(9):2605–2610. [PubMed] [Google Scholar]
  7. De Clercq E., Descamps J., De Somer P., Barr P. J., Jones A. S., Walker R. T. (E)-5-(2-Bromovinyl)-2'-deoxyuridine: a potent and selective anti-herpes agent. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2947–2951. doi: 10.1073/pnas.76.6.2947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Elion G. B., Furman P. A., Fyfe J. A., de Miranda P., Beauchamp L., Schaeffer H. J. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5716–5720. doi: 10.1073/pnas.74.12.5716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Frank K. B., Chiou J. F., Cheng Y. C. Interaction of herpes simplex virus-induced DNA polymerase with 9-(1,3-dihydroxy-2-propoxymethyl)guanine triphosphate. J Biol Chem. 1984 Feb 10;259(3):1566–1569. [PubMed] [Google Scholar]
  10. Furman P. A., St Clair M. H., Fyfe J. A., Rideout J. L., Keller P. M., Elion G. B. Inhibition of herpes simplex virus-induced DNA polymerase activity and viral DNA replication by 9-(2-hydroxyethoxymethyl)guanine and its triphosphate. J Virol. 1979 Oct;32(1):72–77. doi: 10.1128/jvi.32.1.72-77.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fyfe J. A. Differential phosphorylation of (E)-5-(2-bromovinyl)-2'-deoxyuridine monophosphate by thymidylate kinases from herpes simplex viruses types 1 and 2 and varicella zoster virus. Mol Pharmacol. 1982 Mar;21(2):432–437. [PubMed] [Google Scholar]
  12. Grant A. J., Feinberg A., Chou T. C., Watanabe K. A., Fox J. J., Philips F. S. Incorporation of metabolites of 2'-fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine into deoxyribonucleic acid of neoplastic and normal mammalian tissues. Biochem Pharmacol. 1982 Mar 15;31(6):1103–1108. doi: 10.1016/0006-2952(82)90349-5. [DOI] [PubMed] [Google Scholar]
  13. Lopez C., Watanabe K. A., Fox J. J. 2'-fluoro-5-iodo-aracytosine, a potent and selective anti-herpesvirus agent. Antimicrob Agents Chemother. 1980 May;17(5):803–806. doi: 10.1128/aac.17.5.803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miller W. H., Miller R. L. Phosphorylation of acyclovir (acycloguanosine) monophosphate by GMP kinase. J Biol Chem. 1980 Aug 10;255(15):7204–7207. [PubMed] [Google Scholar]
  15. Schinazi R. F., Peters J., Sokol M. K., Nahmias A. J. Therapeutic activities of 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine and -thymine alone and in combination with acyclovir and vidarabine in mice infected intracerebrally with herpes simplex virus. Antimicrob Agents Chemother. 1983 Jul;24(1):95–103. doi: 10.1128/aac.24.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Smith K. O., Galloway K. S., Kennell W. L., Ogilvie K. K., Radatus B. K. A new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxyl]methyl]guanine, highly active in vitro against herpes simplex virus types 1 and 2. Antimicrob Agents Chemother. 1982 Jul;22(1):55–61. doi: 10.1128/aac.22.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Trousdale M. D., Nesburn A. B., Su T. L., Lopez C., Watanabe K. A., Fox J. J. Activity of 1-(2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl)thymine against herpes simplex virus in cell cultures and rabbit eyes. Antimicrob Agents Chemother. 1983 Jun;23(6):808–813. doi: 10.1128/aac.23.6.808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Watanabe K. A., Reichman U., Hirota K., Lopez C., Fox J. J. Nucleosides. 110. Synthesis and antiherpes virus activity of some 2'-fluoro-2'-deoxyarabinofuranosylpyrimidine nucleosides. J Med Chem. 1979 Jan;22(1):21–24. doi: 10.1021/jm00187a005. [DOI] [PubMed] [Google Scholar]
  19. Yoshikawa M., Kato T., Takenishi T. A novel method for phosphorylation of nucleosides to 5'-nucleotides. Tetrahedron Lett. 1967 Dec;50:5065–5068. doi: 10.1016/s0040-4039(01)89915-9. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES