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Chemical Compound Review

Fosfonet sodium     2-phosphonoethanoic acid

Synonyms: Fosfonet, Fosfonoacetate, Lopac-P-6909, Abbott-38642, CHEMBL50300, ...
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Disease relevance of Disodium phosphonoacetate


High impact information on Disodium phosphonoacetate

  • After repeated absorption with PAA-treated B95-8, the serum remains reactive with the membranes of producer cell lines as judged by immunofluorescence or the 125I--Staphylococcal protein A radioimmunoassay [1].
  • Transformation of human lymphocytes by Epstein-Barr virus is inhibited by phosphonoacetic acid [6].
  • Three highly conserved regions of amino acid homology, found in several viral alpha-like DNA polymerases and in the luminal diameter 29 DNA polymerase, one of them proposed to be the PAA binding site, were also found in the T4 DNA polymerase [3].
  • In contrast, the chimeric gene consisting of tk sequence upstream of -16 fused to gamma 2 sequence downstream of -12 had the attributes of both beta and gamma 2 genes in that it was expressed both early and late in infection and was partially resistant to phosphonoacetate [7].
  • The enzyme differs from the cellular DNA polymerases, but resembles herpes-virus-induced DNA polymerase in its primer template preference, high monovalent cation requirement for activity, and sensitivity to phosphonoacetate [8].

Chemical compound and disease context of Disodium phosphonoacetate

  • Immunofluorescence studies showed that greater than or equal to 30 mug/ml of phosphonoacetic acid inhibited viral capsid antigen synthesis without affecting the expression of the nuclear antigen or the spontaneous and 5-iodo-2'-deoxyuridine-induced early antigens [9].
  • Other pyrophosphate analogs, such as phosphonoacetate, were substrates for the excision reaction with both terminated and nonterminated primers, whereas pamidronate, a bisphosphonate that prevents bone resorption, was not a substrate for these reactions and competitively inhibited the phosphorolytic activity of RT [10].
  • The inhibition of PGE2 biosynthesis was relieved when the experiments were conducted in presence of phosphonoacetic acid, an inhibitor of herpesviruses DNA polymerase, indicating that viral replication and/or neosynthesized viral proteins were involved in this process [11].
  • This enzyme has the characteristics of a typical Epstein-Barr virus DNA polymerase with regard to chromatographical pattern and biological properties: it is eluted from DEAE-cellulose at 0.08 M NaCl, has a high salt resistance, is sensitive to phosphonoacetic acid and phosphonoformate, and shows a substrate preference for poly(dC)-oligo(dG12-18) [12].
  • In virus-producing P3HR-1 cultures that were exposed for 11 days to phosphonoacetic acid or to acyclovir, the content of covalently closed circular EBV DNA was reduced ca. 70% relative to a control culture without drug [13].

Biological context of Disodium phosphonoacetate


Anatomical context of Disodium phosphonoacetate


Associations of Disodium phosphonoacetate with other chemical compounds


Gene context of Disodium phosphonoacetate


Analytical, diagnostic and therapeutic context of Disodium phosphonoacetate


  1. Characterization of cross-reacting antigens on the Epstein-Barr virus envelope and plasma membranes of producer cells. Thorley-Lawson, D.A. Cell (1979) [Pubmed]
  2. Effect of phosphonoacetate on Marek's disease virus replication. Lee, L.F., Nazerian, K., Leinbach, S.S., Reno, J.M., Boezi, J.A. J. Natl. Cancer Inst. (1976) [Pubmed]
  3. Structural and functional relationships between prokaryotic and eukaryotic DNA polymerases. Bernad, A., Zaballos, A., Salas, M., Blanco, L. EMBO J. (1987) [Pubmed]
  4. Homology between DNA polymerases of poxviruses, herpesviruses, and adenoviruses: nucleotide sequence of the vaccinia virus DNA polymerase gene. Earl, P.L., Jones, E.V., Moss, B. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  5. Resistance of herpes simplex virus to 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine: physical mapping of drug synergism within the viral DNA polymerase locus. Crumpacker, C.S., Kowalsky, P.N., Oliver, S.A., Schnipper, L.E., Field, A.K. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  6. Transformation of human lymphocytes by Epstein-Barr virus is inhibited by phosphonoacetic acid. Thorley-Lawson, D., Strominger, J.L. Nature (1976) [Pubmed]
  7. Delineation of regulatory domains of early (beta) and late (gamma 2) genes by construction of chimeric genes expressed in herpes simplex virus 1 genomes. Mavromara-Nazos, P., Roizman, B. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  8. Isolation of a herpesvirus-specific DNA polymerase from tissues of an American patient with Burkitt lymphoma. Allaudeen, H.S., Bertino, J.R. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  9. Differential effect of phosphonoacetic acid on the expression of Epstein-Barr viral antigens and virus production. Nyormoi, O., Thorley-Lawson, D.A., Elkington, J., Strominger, J.L. Proc. Natl. Acad. Sci. U.S.A. (1976) [Pubmed]
  10. Selective Excision of Chain-terminating Nucleotides by HIV-1 Reverse Transcriptase with Phosphonoformate as Substrate. Cruchaga, C., Ansó, E., Rouzaut, A., Martínez-Irujo, J.J. J. Biol. Chem. (2006) [Pubmed]
  11. EBV suppresses prostaglandin E2 biosynthesis in human monocytes. Savard, M., Bélanger, C., Tremblay, M.J., Dumais, N., Flamand, L., Borgeat, P., Gosselin, J. J. Immunol. (2000) [Pubmed]
  12. Epstein-Barr virus-specific DNA polymerase in virus-nonproducer Raji cells. Ooka, T., Lenoir, G.M., Decaussin, G., Bornkamm, G.W., Daillie, J. J. Virol. (1986) [Pubmed]
  13. The circular intracellular form of Epstein-Barr virus DNA is amplified by the virus-associated DNA polymerase. Shaw, J.E. J. Virol. (1985) [Pubmed]
  14. Phi 29 DNA polymerase active site. Residue ASP249 of conserved amino acid motif "Dx2SLYP" is critical for synthetic activities. Blasco, M.A., Lázaro, J.M., Blanco, L., Salas, M. J. Biol. Chem. (1993) [Pubmed]
  15. Identification of target antigen for antibody-dependent cellular cytotoxicity on cells carrying Epstein-Barr virus genome. Takaki, K., Harada, M., Sairenji, T., Hinuma, Y. J. Immunol. (1980) [Pubmed]
  16. Herpes simplex virus type 1 DNA polymerase. Mutational analysis of the 3'-5'-exonuclease domain. Kühn, F.J., Knopf, C.W. J. Biol. Chem. (1996) [Pubmed]
  17. Inhibition of Epstein-Barr virus DNA synthesis and late gene expression by phosphonoacetic acid. Summers, W.C., Klein, G. J. Virol. (1976) [Pubmed]
  18. Human cytomegalovirus. IV. Specific inhibition of virus-induced DNA polymerase activity and viral DNA replication by phosphonoacetic acid. Huang, E.S. J. Virol. (1975) [Pubmed]
  19. Mutational analysis of the ICP4 binding sites in the 5' transcribed noncoding domains of the herpes simplex virus 1 UL 49.5 gamma 2 gene. Romanelli, M.G., Mavromara-Nazos, P., Spector, D., Roizman, B. J. Virol. (1992) [Pubmed]
  20. Synthesis of herpes simplex virus, vaccinia virus, and adenovirus DNA in isolated HeLa cell nuclei. I. Effect of viral-specific antisera and phosphonoacetic acid. Bolden, A., Aucker, J., Weissbach, A. J. Virol. (1975) [Pubmed]
  21. De novo infection and serial transmission of Kaposi's sarcoma-associated herpesvirus in cultured endothelial cells. Lagunoff, M., Bechtel, J., Venetsanakos, E., Roy, A.M., Abbey, N., Herndier, B., McMahon, M., Ganem, D. J. Virol. (2002) [Pubmed]
  22. Identification of a unique Marek's disease virus gene which encodes a 38-kilodalton phosphoprotein and is expressed in both lytically infected cells and latently infected lymphoblastoid tumor cells. Chen, X.B., Sondermeijer, P.J., Velicer, L.F. J. Virol. (1992) [Pubmed]
  23. Motif A of bacteriophage T4 DNA polymerase: role in primer extension and DNA replication fidelity. Isolation of new antimutator and mutator DNA polymerases. Reha-Krantz, L.J., Nonay, R.L. J. Biol. Chem. (1994) [Pubmed]
  24. Identification, expression, and immunogenicity of Kaposi's sarcoma-associated herpesvirus-encoded small viral capsid antigen. Lin, S.F., Sun, R., Heston, L., Gradoville, L., Shedd, D., Haglund, K., Rigsby, M., Miller, G. J. Virol. (1997) [Pubmed]
  25. Promoter sequences required for reactivation of Epstein-Barr virus from latency. Binné, U.K., Amon, W., Farrell, P.J. J. Virol. (2002) [Pubmed]
  26. Herpes simplex virus 1 infection activates the endoplasmic reticulum resident kinase PERK and mediates eIF-2alpha dephosphorylation by the gamma(1)34.5 protein. Cheng, G., Feng, Z., He, B. J. Virol. (2005) [Pubmed]
  27. Evidence that the UL84 gene product of human cytomegalovirus is essential for promoting oriLyt-dependent DNA replication and formation of replication compartments in cotransfection assays. Sarisky, R.T., Hayward, G.S. J. Virol. (1996) [Pubmed]
  28. Novel activation of gamma-interferon in nonimmune cells during human cytomegalovirus replication. Boldogh, I., Bui, T.K., Szaniszlo, P., Bresnahan, W.A., Albrecht, T., Hughes, T.K. Proc. Soc. Exp. Biol. Med. (1997) [Pubmed]
  29. Effects of human alpha, beta and gamma interferons on varicella zoster virus in vitro. Balachandra, K., Thawaranantha, D., Ayuthaya, P.I., Bhumisawasdi, J., Shiraki, K., Yamanishi, K. Southeast Asian J. Trop. Med. Public Health (1994) [Pubmed]
  30. Architecture of replication compartments formed during Epstein-Barr virus lytic replication. Daikoku, T., Kudoh, A., Fujita, M., Sugaya, Y., Isomura, H., Shirata, N., Tsurumi, T. J. Virol. (2005) [Pubmed]
  31. Herpes simplex virus type 1 prereplicative sites are a heterogeneous population: only a subset are likely to be precursors to replication compartments. Lukonis, C.J., Burkham, J., Weller, S.K. J. Virol. (1997) [Pubmed]
  32. Identification, localization, and regulation of expression of the UL24 protein of herpes simplex virus type 1. Pearson, A., Coen, D.M. J. Virol. (2002) [Pubmed]
  33. Identification, analysis, and evolutionary relationships of the putative murine cytomegalovirus homologs of the human cytomegalovirus UL82 (pp71) and UL83 (pp65) matrix phosphoproteins. Cranmer, L.D., Clark, C.L., Morello, C.S., Farrell, H.E., Rawlinson, W.D., Spector, D.H. J. Virol. (1996) [Pubmed]
  34. Mapping of the vaccinia virus DNA polymerase gene by marker rescue and cell-free translation of selected RNA. Jones, E.V., Moss, B. J. Virol. (1984) [Pubmed]
  35. Identification and characterization of an equine herpesvirus 1 late gene encoding a potential zinc finger. Holden, V.R., Yalamanchili, R.R., Harty, R.N., O'Callaghan, D.J. Virology (1992) [Pubmed]
  36. Conserved core structure and active site residues in alkaline phosphatase superfamily enzymes. Galperin, M.Y., Jedrzejas, M.J. Proteins (2001) [Pubmed]
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