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. 1987 Sep 11;15(17):6991–7004. doi: 10.1093/nar/15.17.6991

Synthesis and resistance to enzymic hydrolysis of stereochemically-defined phosphonate and thiophosphate analogues of P1,P4-bis(5'-adenosyl) tetraphosphate.

G M Blackburn 1, G E Taylor 1, G R Thatcher 1, M Prescott 1, A G McLennan 1
PMCID: PMC306188  PMID: 2821489

Abstract

Novel analogues of P1,P4-bis(5'-adenosyl) tetraphosphate, Ap4A (1), have been prepared with sulphur substituents at P1 and P4 and either oxygen or methylene bridges at the P2,P3-position. Separation of three isomers of the ApspCH2ppsA species has been achieved by a combination of mplc and hplc and the Rp,Rp, Rp,Sp, and Sp,Sp diastereoisomers identified on the basis of selective enzymatic hydrolysis using snake venom phosphodiesterase. Each of these three isomers is a strong competitive inhibitor of the specific Ap4Aase from Artemia and is highly resistant to the asymmetric cleavage normally catalysed by this enzyme.

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Selected References

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  1. Baker J. C., Jacobson M. K. Alteration of adenyl dinucleotide metabolism by environmental stress. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2350–2352. doi: 10.1073/pnas.83.8.2350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baltzinger M., Ebel J. P., Remy P. Accumulation of dinucleoside polyphosphates in Saccharomyces cerevisiae under stress conditions. High levels are associated with cell death. Biochimie. 1986 Oct-Nov;68(10-11):1231–1236. doi: 10.1016/s0300-9084(86)80069-4. [DOI] [PubMed] [Google Scholar]
  3. Bambara R. A., Crute J. J., Wahl A. F. Is Ap4A an activator of eukaryotic DNA replication? Cancer Invest. 1985;3(5):473–479. doi: 10.3109/07357908509039809. [DOI] [PubMed] [Google Scholar]
  4. Baril E. F., Coughlin S. A., Zamecnik P. C. 5',5'''-P1, P4 diadenosine tetraphosphate (Ap4A): a putative initiator of DNA replication. Cancer Invest. 1985;3(5):465–471. doi: 10.3109/07357908509039808. [DOI] [PubMed] [Google Scholar]
  5. Barnes L. D., Culver C. A. Isolation and characterization of diadenosine 5',5"'-P1,P4-tetraphosphate pyrophosphohydrolase from Physarum polycephalum. Biochemistry. 1982 Nov 23;21(24):6123–6128. doi: 10.1021/bi00267a015. [DOI] [PubMed] [Google Scholar]
  6. Blanquet S., Plateau P., Brevet A. The role of zinc in 5',5'-diadenosine tetraphosphate production by aminoacyl-transfer RNA synthetases. Mol Cell Biochem. 1983;52(1):3–11. doi: 10.1007/BF00230583. [DOI] [PubMed] [Google Scholar]
  7. Bochner B. R., Lee P. C., Wilson S. W., Cutler C. W., Ames B. N. AppppA and related adenylylated nucleotides are synthesized as a consequence of oxidation stress. Cell. 1984 May;37(1):225–232. doi: 10.1016/0092-8674(84)90318-0. [DOI] [PubMed] [Google Scholar]
  8. Brevet A., Plateau P., Best-Belpomme M., Blanquet S. Variation of Ap4A and other dinucleoside polyphosphates in stressed Drosophila cells. J Biol Chem. 1985 Dec 15;260(29):15566–15570. [PubMed] [Google Scholar]
  9. Bryant F. R., Benkovic S. J. Stereochemical course of the reaction catalyzed by 5'-nucleotide phosphodiesterase from snake venom. Biochemistry. 1979 Jun 26;18(13):2825–2828. doi: 10.1021/bi00580a022. [DOI] [PubMed] [Google Scholar]
  10. Burgers P. M., Eckstein F. Absolute configuration of the diastereomers of adenosine 5'-O-(1-thiotriphosphate): consequences for the stereochemistry of polymerization by DNA-dependent RNA polymerase from Escherichia coli. Proc Natl Acad Sci U S A. 1978 Oct;75(10):4798–4800. doi: 10.1073/pnas.75.10.4798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cameselle J. C., Costas M. J., Günther Sillero M. A., Sillero A. Two low Km hydrolytic activities on dinucleoside 5',5"'-P1,P4-tetraphosphates in rat liver. Characterization as the specific dinucleoside tetraphosphatase and a phosphodiesterase I-like enzyme. J Biol Chem. 1984 Mar 10;259(5):2879–2885. [PubMed] [Google Scholar]
  12. Cameselle J. C., Costas M. J., Sillero M. A., Sillero A. Dinucleosidetetraphosphatase inhibition by Zn(II). Biochem Biophys Res Commun. 1983 Jun 15;113(2):717–722. doi: 10.1016/0006-291x(83)91785-0. [DOI] [PubMed] [Google Scholar]
  13. Chen J. T., Benkovic S. J. Synthesis and separation of diastereomers of deoxynucleoside 5'-O-(1-thio)triphosphates. Nucleic Acids Res. 1983 Jun 11;11(11):3737–3751. doi: 10.1093/nar/11.11.3737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Garrison P. N., Mathis S. A., Barnes L. D. In vivo levels of diadenosine tetraphosphate and adenosine tetraphospho-guanosine in Physarum polycephalum during the cell cycle and oxidative stress. Mol Cell Biol. 1986 Apr;6(4):1179–1186. doi: 10.1128/mcb.6.4.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goerlich O., Foeckler R., Holler E. Mechanism of synthesis of adenosine(5')tetraphospho(5')adenosine (AppppA) by aminoacyl-tRNA synthetases. Eur J Biochem. 1982 Aug;126(1):135–142. doi: 10.1111/j.1432-1033.1982.tb06757.x. [DOI] [PubMed] [Google Scholar]
  16. Grummt F. Diadenosine 5',5'''-P1,P4-tetraphosphate triggers initiation of in vitro DNA replication in baby hamster kidney cells. Proc Natl Acad Sci U S A. 1978 Jan;75(1):371–375. doi: 10.1073/pnas.75.1.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Grummt F., Waltl G., Jantzen H. M., Hamprecht K., Huebscher U., Kuenzle C. C. Diadenosine 5',5'''-P1,P4-tetraphosphate, a ligand of the 57-kilodalton subunit of DNA polymerase alpha. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6081–6085. doi: 10.1073/pnas.76.12.6081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Guranowski A., Blanquet S. Phosphorolytic cleavage of diadenosine 5',5'''-P1,P4-tetraphosphate. Properties of homogeneous diadenosine 5',5'''-P1,P4-tetraphosphate alpha, beta-phosphorylase from Saccharomyces cerevisiae. J Biol Chem. 1985 Mar 25;260(6):3542–3547. [PubMed] [Google Scholar]
  19. Guranowski A., Jakubowski H., Holler E. Catabolism of diadenosine 5',5"'-P1,P4-tetraphosphate in procaryotes. Purification and properties of diadenosine 5',5"'-P1,P4-tetraphosphate (symmetrical) pyrophosphohydrolase from Escherichia coli K12. J Biol Chem. 1983 Dec 25;258(24):14784–14789. [PubMed] [Google Scholar]
  20. Guédon G. F., Gilson G. J., Ebel J. P., Befort N. M., Remy P. M. Lack of correlation between extensive accumulation of bisnucleoside polyphosphates and the heat-shock response in eukaryotic cells. J Biol Chem. 1986 Dec 15;261(35):16459–16465. [PubMed] [Google Scholar]
  21. Holmes A. M., Cheriathundam E., Bollum F. J., Chang L. M. Initiation of DNA synthesis by the calf thymus DNA polymerase-primase complex. J Biol Chem. 1985 Sep 5;260(19):10840–10846. [PubMed] [Google Scholar]
  22. Höhn M., Albert W., Grummt F. Diadenosine tetraphosphate hydrolase from mouse liver. Purification to homogeneity and partial characterization. J Biol Chem. 1982 Mar 25;257(6):3003–3006. [PubMed] [Google Scholar]
  23. Jakubowski H., Guranowski A. Enzymes hydrolyzing ApppA and/or AppppA in higher plants. Purification and some properties of diadenosine triphosphatase, diadenosine tetraphosphatase, and phosphodiesterase from yellow lupin (Lupinus luteus) seeds. J Biol Chem. 1983 Aug 25;258(16):9982–9989. [PubMed] [Google Scholar]
  24. Lee P. C., Bochner B. R., Ames B. N. AppppA, heat-shock stress, and cell oxidation. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7496–7500. doi: 10.1073/pnas.80.24.7496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McLennan A. G., Prescott M. Diadenosine 5',5'"-P1,P4-tetraphosphate in developing embryos of Artemia. Nucleic Acids Res. 1984 Feb 10;12(3):1609–1619. doi: 10.1093/nar/12.3.1609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miller D., McLennan A. G. Changes in intracellular levels of Ap3A and Ap4A in cysts and larvae of Artemia do not correlate with changes in protein synthesis after heat-shock. Nucleic Acids Res. 1986 Aug 11;14(15):6031–6040. doi: 10.1093/nar/14.15.6031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Moreno A., Lobatón C. D., Sillero M. A., Sillero A. Dinucleosidetetraphosphatase from Ehrlich ascites tumour cells: inhibition by adenosine, guanosine and uridine 5'-tetraphosphates. Int J Biochem. 1982;14(7):629–634. doi: 10.1016/0020-711x(82)90047-7. [DOI] [PubMed] [Google Scholar]
  28. Morioka M., Shimada H. Nuclear AP4A-binding activity of sea urchin embryos changes in relation to the initiation of S phase. Exp Cell Res. 1986 Aug;165(2):429–440. doi: 10.1016/0014-4827(86)90596-3. [DOI] [PubMed] [Google Scholar]
  29. Ogilvie A., Antl W. Diadenosine tetraphosphatase from human leukemia cells. Purification to homogeneity and partial characterization. J Biol Chem. 1983 Apr 10;258(7):4105–4109. [PubMed] [Google Scholar]
  30. Plateau P., Fromant M., Brevet A., Gesquière A., Blanquet S. Catabolism of bis(5'-nucleosidyl) oligophosphates in Escherichia coli: metal requirements and substrate specificity of homogeneous diadenosine-5',5'''-P1,P4-tetraphosphate pyrophosphohydrolase. Biochemistry. 1985 Feb 12;24(4):914–922. doi: 10.1021/bi00325a016. [DOI] [PubMed] [Google Scholar]
  31. Rapaport E., Feldman L. Adenosine(5')tetraphospho(5')adenosine-binding protein of calf thymus. Eur J Biochem. 1984 Jan 2;138(1):111–115. doi: 10.1111/j.1432-1033.1984.tb07888.x. [DOI] [PubMed] [Google Scholar]
  32. Rapaport E., Zamecnik P. C., Baril E. F. Association of diadenosine 5',5"'-P1,P4-tetraphosphate binding protein with HeLa cell DNA polymerase alpha. J Biol Chem. 1981 Dec 10;256(23):12148–12151. [PubMed] [Google Scholar]
  33. Rapaport E., Zamecnik P. C. Presence of diadenosine 5',5''' -P1, P4-tetraphosphate (Ap4A) in mamalian cells in levels varying widely with proliferative activity of the tissue: a possible positive "pleiotypic activator". Proc Natl Acad Sci U S A. 1976 Nov;73(11):3984–3988. doi: 10.1073/pnas.73.11.3984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Segal E., Le Pecq J. B. Relationship between cellular diadenosine 5',5'''-P1,P4-tetraphosphate level, cell density, cell growth stimulation and toxic stresses. Exp Cell Res. 1986 Nov;167(1):119–126. doi: 10.1016/0014-4827(86)90209-0. [DOI] [PubMed] [Google Scholar]
  35. Surowy C. S., Berger N. A. Diadenosine 5', 5"'-P1,P4-tetraphosphate stimulates processing of adp-ribosylated poly(ADP-ribose) polymerase. J Biol Chem. 1983 Jan 10;258(1):579–583. [PubMed] [Google Scholar]
  36. Tanaka Y., Matsunami N., Itaya A., Yoshihara K. Histone-dependent ADP-ribosylation of low molecular nucleotide by poly(ADP-ribose) polymerase. J Biochem. 1981 Oct;90(4):1131–1139. doi: 10.1093/oxfordjournals.jbchem.a133565. [DOI] [PubMed] [Google Scholar]
  37. Vallejo C. G., Lobaton C. D., Quintanilla M., Sillero A., Sillero M. A. Dinucleosidasetetraphosphatase in rat liver and Artemia salina. Biochim Biophys Acta. 1976 Jun 7;438(1):304–309. doi: 10.1016/0005-2744(76)90246-1. [DOI] [PubMed] [Google Scholar]
  38. Varshavsky A. Do stalled replication forks synthesize a specific alarmone? J Theor Biol. 1983 Dec 21;105(4):707–714. doi: 10.1016/0022-5193(83)90228-x. [DOI] [PubMed] [Google Scholar]
  39. Weinmann-Dorsch C., Grummt F. Diadenosine tetraphosphate (Ap4A) is compartmentalized in nuclei of mammalian cells. Exp Cell Res. 1986 Aug;165(2):550–554. doi: 10.1016/0014-4827(86)90607-5. [DOI] [PubMed] [Google Scholar]
  40. Weinmann-Dorsch C., Hedl A., Grummt I., Albert W., Ferdinand F. J., Friis R. R., Pierron G., Moll W., Grummt F. Drastic rise of intracellular adenosine(5')tetraphospho(5')adenosine correlates with onset of DNA synthesis in eukaryotic cells. Eur J Biochem. 1984 Jan 2;138(1):179–185. doi: 10.1111/j.1432-1033.1984.tb07897.x. [DOI] [PubMed] [Google Scholar]
  41. Weinmann-Dorsch C., Pierron G., Wick R., Sauer H., Grummt F. High diadenosine tetraphosphate (Ap4A) level at initiation of S phase in the naturally synchronous mitotic cycle of Physarum polycephalum. Exp Cell Res. 1984 Nov;155(1):171–177. doi: 10.1016/0014-4827(84)90778-x. [DOI] [PubMed] [Google Scholar]
  42. Zamecnik P. C., Rapaport E., Baril E. F. Priming of DNA synthesis by diadenosine 5',5"'-P1,P4-tetraphosphate with a double-stranded octadecamer as a template and DNA polymerase alpha. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1791–1794. doi: 10.1073/pnas.79.6.1791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Zamecnik P. C., Stephenson M. L., Janeway C. M., Randerath K. Enzymatic synthesis of diadenosine tetraphosphate and diadenosine triphosphate with a purified lysyl-sRNA synthetase. Biochem Biophys Res Commun. 1966 Jul 6;24(1):91–97. doi: 10.1016/0006-291x(66)90415-3. [DOI] [PubMed] [Google Scholar]

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