Skip to main content
SpringerLink
Log in

Phosphorylating Enzymes Involved in Activation of Chemotherapeutic Nucleosides and Nucleotides

  • Conference paper
Molecular Aspects of Chemotherapy

Abstract

A brief survey is presented of the enzymes responsible for the activation (by phosphorylation) of chemotherapeutically active nucleoside analogues, including acyclonucleosides, dideoxynucleosides, and the recently reported oxetanocin and cyclobut (carbocyclic oxetanocin) nucleosides, and relevance to the latter of 3′-branched 2′-deoxynucleosides. Properties of the known cellular and viral-encoded nucleoside kinases, and nucleoside phosphotransferases (cytosolic 5′-nucleotidases) are described. Phosphates and cyclic phosphates of acyclonucleosides with more than one hydroxyl in the acyclic chain, and their behaviour towards a variety of enzymes, are examined in relation to the possible mechanism of antiviral activity of the cyclic phosphate of Ganciclovir, which is an analogue of cGMP. Reported observations on the role of cAMP and cGMP on viral replication are briefly reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kugmierek JT and Shugar D, Nucleotides, nucleoside phosphate diesters and phosphonates as antiviral and antineoplastic agents — an overview. In: Antiviral Mechanisms in the Control of Neoplasia (Chandra P, ed), pp. 481–498, Plenum Press, NY, 1979.

    Google Scholar 

  2. Martin JC (ed), Nucleotide Analogues as Antiviral Agents. ACS Symp Ser No. 401, American Chemical Society, Washington, 1989.

    Google Scholar 

  3. De Clercq E, Broad-spectrum anti-DNA virus and anti-retrovirus activity of phosphonylmethoxyalkylpurines and pyrimidines. Biochem. Pharmacol 42: 963–972, 1991.

    Article  PubMed  Google Scholar 

  4. Balzarini J and De Clercq E, 5-Phosphoribosyl 1-pyrophosphate synthetase converts the acyclic nucleoside phosphonates 9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and 9-(2-phs-phonylmethoxyethyl)adenine directly to their antivirally active diphosphate derivatives. J. Biol. Chem 266: 8686–8689, 1991.

    PubMed  CAS  Google Scholar 

  5. Rose WC, Crosswell AR, Bronson JJ and Martin JC, In vivo antitumour activity of 9-[(2-phosphonylmethoxy)ethyl]guanine and related phosphonate nucleotide analogues. J. Nat. Cancer Inst 82: 510–512, 1990.

    Article  PubMed  CAS  Google Scholar 

  6. Tanaka H, Baba M, Saito S, Miyasaka T, Takashima H, Sekiya K, Ubasawa M, Mitta I, Walker RT, Nakashima H and De Clercq E, Specific anti-HIV-1 acyclonucleosides which cannot be phosphorylated—Synthesis of some deoxy analogues of 1-[(2-hydroxyethoxy)methyl]6(phenylthio)thymine. J. Med. Chem 34: 1508–1511, 1991.

    Article  PubMed  CAS  Google Scholar 

  7. Wright GE and Brown NC, Deoxyribonucleotide analogs as inhibitors and substrates of DNA polymerases. Pharmacol. Ther 47: 437–497, 1990.

    Article  Google Scholar 

  8. Tolman RL, Field AK, Karkas JD, Wagner AF, Germershausen J, Crumpacker C and Scolnick EM, 2’-nor-cGMP: a seco cyclic nucleotide with powerful anti-DNA-viral activity. Biochem. Biophys. Res. Commun 128: 1329–1335, 1985.

    Article  PubMed  CAS  Google Scholar 

  9. Yang ZH, Lucia HL, Tolman RL, Colonno RJ and Hsiung GD, Effect of 2’-nor-cyclic GMP against guinea pig cytomegalovirus infection, Antimicrob. Agents Chemother 33: 1563–1568, 1989.

    Article  PubMed  CAS  Google Scholar 

  10. Germerhausen J, Bostedor R, Liou R, Field AK, Wagner AF, MacCoss M, Tolman RL and Karkas JD, Comparison of the modes of antiviral action of 2’-nor-deoxyguanosine nad its cyclic phosphate, 2’-nor-cyclic GMP. Antimicrob. Agents Chemother 29: 1025–1031, 1986.

    Article  Google Scholar 

  11. Tihon C and Green M, Cyclic AMP-amplified replication of RNA tumour virus-like particles in Chinese hamster ovary cells. Nature New. Biol 244: 227–231, 1973.

    Article  CAS  Google Scholar 

  12. Stanwick TL, Anderson RW and Nahmias AJ, Interaction between cyclic nucleotides and herpes simplex viruses: Productive infection. Infect. Immun 18: 342–347, 1977.

    PubMed  CAS  Google Scholar 

  13. Robbins SJ and Rapp F, Inhibition of measles virus replication by cyclic AMP. Virology 106: 317–326, 1980.

    Article  PubMed  CAS  Google Scholar 

  14. Miller CA and Carrigan DR, Reversible repression and activation of measles virus infection in neural cells. Proc. Natl. Acad. Sci. USA 79: 1629–1623, 1982.

    Article  PubMed  CAS  Google Scholar 

  15. Robbins SJ, Stimulation of measles virus replication by cyclic guanosine monophosphate. Intervirology 32: 204–208, 1991.

    PubMed  CAS  Google Scholar 

  16. Cho-Chung YS, Clair T, Tortero G and Yokozaki H, Role of site-selective cAMP analogs in control and reversal of malignacy. Pharmacol. Ther 50: 1–33, 1991.

    Article  PubMed  CAS  Google Scholar 

  17. Prisbe EJ, Martin JC, McGee DPC, Barker MF, Smee DF, Duke AE, Matthews TR and Verheyden JPH, Synthesis and antiherpes virus activity of phosphate and phosphonate derivatives of 9-(1,3-dihydroxy-2-propoxy)methyl guanine. J. Med. Chem 29: 671–675, 1986.

    Article  PubMed  CAS  Google Scholar 

  18. Karkas JD, Germershausen J, Tolman RL, MacCoss M, Wagner AF, Liou R and Bostedor R, Stereochemical considerations in the enzymatic phosphorylation and antiviral activity of acyclonucleosides. I. Phosphorylation of 2’-nor-2’-deoxyguanosine. Biochim. Biophys. Acta 911: 127–135, 1987.

    Article  PubMed  CAS  Google Scholar 

  19. Lassota P, Kazimierczuk Z, Zan-Kowalczewska M and Shugar D, 2’,3’-seco pyrimidine nucleosides and nucleotides, including structural analogues of 3’:5’-cyclic CMP and UMP, and their behaviour in several enzyme systems. Biochem. Biophys. Res. Commun 137: 453–460, 1986.

    Article  PubMed  CAS  Google Scholar 

  20. Stolarski R, Kazimierczuk Z, Lassota P and Shugar D, Acyclo nucleosides and nucleotides: Synthesis, conformation and other properties, and behaviour in some enzyme systems, of 2’,3’-seco purine nucleosides, nucleotides and 3’:5’-cyclic phosphates, analogues of cAMP and cGMP. Z. Naturforsch. 41c: 758–770, 1986.

    CAS  Google Scholar 

  21. Stolarski R, Lassota P, Kazimierczuk Z and Shugar D, Solution conformations of some acyclonucleoside and nucleotide analogues of antiviral acyclonucleosides, and their substrate/inhibitor properties in several enzyme systems. Z. Naturforsch 43c: 231–242, 1988.

    CAS  Google Scholar 

  22. Stolarski R, Ciesla JM and Shugar D, Monophosphates and cyclic phosphates of some antiviral acyclonucleosides: Synthesis, conformation and substrate/inhibitor properties in some enzyme systems. Z. Naturforsch. 45c: 293–299, 1990.

    CAS  Google Scholar 

  23. Zan-Kowalczewska M, Ciesla JM, Sierakowska H and Shugar D, Potato tuber cyclic-nucleotide phosphodiesterase. Selective inactivation of activity vs nucleoside cyclic 3’,5’-phosphates and properties of the native and selectively inactived enzyme. Biochemistry 26: 1194–1200, 1987.

    Article  CAS  Google Scholar 

  24. Helfman DM and Kuo JF, A homogenous cyclic CMP phosphodiesterase hydrolyzes both pyrimidine and purine cyclic 2’:3’- and 3’:5’-nucleotides. J. Biol. Chem 257: 1044–1047, 1982.

    PubMed  CAS  Google Scholar 

  25. Chiatante D, Newton RP and Brown EG, Properties of a multifunctional 3’,5’-cyclic nucleotide phosphodiesterase from Lectuca cotyedons: Comparison with mammalian enzymes capable of hydrolysing pyrimidine cyclic nucleotides. Phytochemistry 26: 1301–1306, 1987.

    Article  CAS  Google Scholar 

  26. Eriksson S, Kierdaszuk B, Munch-Petersen B, Oberg O and Johansson NG, Comparison of the substrate specificities of human thymidine kinases 1 and 2 and deoxycytidine kinase toward antiviral and cytostatic nucleoside analogs. Biochem. Biophys. Res. Commun 176: 586–592, 1991.

    Article  PubMed  CAS  Google Scholar 

  27. Munch-Petersen B, Cloos L, Tyrsted G and Eriksson S, Diverging substrate specificity of pure human thymidine kinases 1 and 2 against antiviral dideoxynucleosides. J. Biol. Chem 266: 9032–9038, 1991.

    PubMed  CAS  Google Scholar 

  28. Plagemann PGW, Behrens M and Abraham D, Metabolism and cytotoxicity of 5-azacytidine in cultured Novikoff rat hepatoma and P388 Leukemia cells and their enhancement by preincubation with pyrazofurin. Cancer Res. 38: 2458–2466, 1978.

    PubMed  CAS  Google Scholar 

  29. Payne RC, Cheng N and Traut W, Uridine kinase from Ehrlich ascites carcinoma: Purification and properties of homogenous enzyme. J. Biol. Chem 260: 10242–10247, 1985.

    PubMed  CAS  Google Scholar 

  30. Park I and Ives DH, Properties of a highly purified mitochondrial deoxyguanosine kinase. Arch. Biochem. Biophys 266: 51–60, 1988.

    Article  PubMed  CAS  Google Scholar 

  31. Lewis RA and Link L, Phosphorylation of arabinosyl guanine by a mitochondrial enzyme of bovine liver. Biochem. Pharmacol 38: 2001–2006, 1989.

    Article  PubMed  CAS  Google Scholar 

  32. Miller WH and Miller RL, Guanosine kinase from Trichomonas vaginalis. Mol. Biochem. Parasitol. 48: 39–46, 1991.

    Article  CAS  Google Scholar 

  33. Kong X-B, Tong WP and Chou T-C, Induction of deoxycytidine kinase by 5-azacytidine in an HL-60 cell line resistant to arabinosylcytosine. Mol. Pharmacol 39: 250–257, 1991.

    PubMed  CAS  Google Scholar 

  34. Fyfe JA, 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 21: 432–437, 1982.

    PubMed  CAS  Google Scholar 

  35. MacCoss M, Tolman RL, Ashton WT, Wagner AF, Hannah J, Field AK, Karkas JD and Germershausen JI, Synthetic, biochemical and antiviral aspects of selected acyclonucleosides and their derivatives. Chemica Scripta 26: 113–121, 1986.

    CAS  Google Scholar 

  36. Ikeda S, Chakravarty R and Ives DH, Multisubstrate analogs for deoxynucleoside kinases. J. Biol. Chem 261: 15836–15843, 1986.

    PubMed  CAS  Google Scholar 

  37. Bone R, Cheng Y-C and Wolfenden R, Inhibition of thymidine kinase by P1-(Adenosine-5’)-P5(thymidine-5’)-pentaphosphate. J. Biol. Chem 261: 5731–5735, 1986.

    PubMed  CAS  Google Scholar 

  38. Davies LC, Stock JA, Barrie SE, Orr RM and Harrap KR, Dinucleotide analogues as inhibitors of thymidine kinase, thymidylate kinase and ribonucleotide reductase. J. Med. Chem 31: 1305–1308, 1988.

    Article  PubMed  CAS  Google Scholar 

  39. Broom AD, Rational design of enzyme inhibitors: Multisubstrate analogue inhibitors. J. Med. Chem 32: 2–7, 1988.

    Article  Google Scholar 

  40. Miller RL, Adamczyk DL, Miller WH, Koszalka GW, Rideout JL, Beacham III LM, Chao EY, Haggerty JJ, Krenitsky TA and Elion GB, Adenosine kinase from rabbit liver. II. Substrate and inhibitor specificity. J. Biol. Chem 254: 2346–2352, 1979.

    PubMed  CAS  Google Scholar 

  41. LaFon SW, Nelson DJ, Berens RL and Man JJ, Inosine analogues: Their metabolism in L cells and in Leishmania donovani. J. Biol. Chem. 260: 9660–9665, 1986.

    Google Scholar 

  42. Nutter LM, Grill SP, Dutschman GE, Sharma RA, Bobek M and Cheng Y-C, Demonstration of viral thymidine kinase inhibitor and its effect on deoxyribonucleotide metabolism in cells infected with herpes simplex virus. Antimicrob. Agents Chemother 31: 368–374, 1987.

    Article  PubMed  CAS  Google Scholar 

  43. Ashton WT, Meurer LC, Tolman RL, Karkas JD, Liou R, Perry HC, Czelusniak SM and Klein RJ, A potent selective non-substrate inhibitor of HSV-1 thymidine kinase: (±)-9-[{(Z)-2(hydroxymethyl)cyclohexyl]methyl]guanine and related compounds. Nucleosides Nucleotides 8: 1157–1158, 1989.

    Article  Google Scholar 

  44. Hildebrand C, Sandoli D, Focher F, Gambino J, Ciarrochi G, Spadari S and Wright G, Structure-activity relationships of N2-substituted guanines as inhibitors of HSV-1 and HSV-2 thymidine kinases. J. Med. Chem 33: 203–206, 1990.

    Article  PubMed  CAS  Google Scholar 

  45. Swierkowski M and Shugar D, A nonmutagenic thymidine analog with antiviral activity: 5-Ethyldeoxyuridine. J. Med. Chem 12: 533–534, 1969.

    Article  PubMed  CAS  Google Scholar 

  46. Martin JA, Duncan LB, Hall MJ, Wong-Kai-In P, Lambert RW and Thomas GJ, New potent selective inhibitors of herpes simplex virus thymidine kinases. Nucleosides Nucleotides 8: 753–764, 1989.

    Article  Google Scholar 

  47. Spadari S and Wright G, Antivirals based on inhibition of herpesvirus thymidine kinases. Drug News Perspect 2: 333–336, 1989.

    Google Scholar 

  48. Datta AK and Pugano JS, Phosphorylation of Acyclovir in activated Burkitt somatic cell hybrids. Antimicrob. Agents Chemother 24: 10–14, 1983.

    Article  PubMed  CAS  Google Scholar 

  49. Keller PM, McKee SA and Fyfe JA, Cytoplasmic 5’-nucleotidase catalyzes acyclovir phosphorylation. J. Biol. Chem 260: 8664–8667, 1985.

    PubMed  CAS  Google Scholar 

  50. Itoh R, Purification and some properties of cytosolic 5’-nucleotidase from rat liver. Biochim. Biophys. Acta 657: 402–410, 1981.

    Article  PubMed  CAS  Google Scholar 

  51. Worku Y and Newby AC, Nucleoside exchange catalyzed by the cytoplasmic 5’-nucleotidase. Biochem. J 205: 503–510, 1982.

    PubMed  CAS  Google Scholar 

  52. Smee DF, Boehme R, Chernow M, Binko BP and Matthews TR, Intracellular metabolism and enzymatic phosphorylation of 9-(1,3-dihydroxy-2-propoxymethyl)guanine and acyclovir in herpes simplex virus-infected and uninfected cells. Biochem. Pharmacol 34: 1049–1056, 1985.

    Article  PubMed  CAS  Google Scholar 

  53. Birnbaum GI, Cygler H, Kusmierek JT and Shugar D, Structure and conformation of the potent antiherpes agent 9-(2-hydroxyethoxymethyl)guanine (Acycloguanosine). Biochem. Biophys. Res. Commun 103: 968–974, 1981.

    Article  PubMed  CAS  Google Scholar 

  54. Prasher DC, Can MC, Ives DH, Tsai T-C and Frey PA, Nucleoside phosphotransferase from barley. Characterization and evidence for ping-pong kinetics involving phosphoryl enzyme. J. Biol. Chem 257: 4931–4939, 1982.

    PubMed  CAS  Google Scholar 

  55. Billich A, Stockhowe U and Witzel H, Nucleoside phosphotransferase from malt sprouts. I. Isolation, characterization and specificity of the enzyme. Biol. Chem. Hoppe-Seyler 367: 267–278, 1986.

    Article  PubMed  CAS  Google Scholar 

  56. Lassota P, Kusmierek JT, Stolarski R and Shugar D, Pyrimidine homoribonucleosides: Synthesis, solution conformation and some biological properties. Z. Naturforsch 42c: 589–598, 1987.

    CAS  Google Scholar 

  57. Giziewicz J and Shugar D, Preparative enzymatic synthesis of nucleoside-5’-phosphates. Acta Biochim. Polon 22: 87–98, 1975.

    PubMed  CAS  Google Scholar 

  58. Giziewicz J and Shugar D, Nucleoside 5’-phosphates: Enzymatic phosphorylation of nucleosides to the 5’-phosphates. In: Nucleic Acid Chemistry, Part II (Townsend LB and Tipson RS, eds), pp. 955–961, John Wiley and Sons, New York, 1978.

    Google Scholar 

  59. Mizote T and Nakayama H, Purification and properties of hydroxymethylpyrimidine kinase from Escherichia coli. Biochim. Biophys. Acta 991: 109–113, 1989.

    Article  CAS  Google Scholar 

  60. Kit S, Leung W-C, Trkula D and Dubbs DR, Characterization of nucleoside phosphotransferases and thymidine kinase activities of chick embryo cells and chick-mouse somatic cell hybrids. Arch. Biochem. Biophys. 169: 66–76, 1975.

    Article  PubMed  CAS  Google Scholar 

  61. Zekri M, Harb J, Bernard S and Mefla K, Purification of bovine liver cytosolic 5’-nucleotidase: kinetic and structural studies as compared to the membrane isoenzyme. Eur. J. Biochem 172: 93–99, 1988.

    Article  PubMed  CAS  Google Scholar 

  62. Hoglund L and Reichard P, Cytoplasmic 5’(3’)-nucleotidases from human placenta. J. Biol. Chem 265: 6589–6595, 1990.

    PubMed  CAS  Google Scholar 

  63. Fridland A, Connelly MC and Robbins TJ, Tiazofurin metabolism in human lymphoblastoid cells: Evidence for phosphorylation by adenosine kinase and 5’-nucleotidase. Cancer Res. 46: 532–537, 1986.

    PubMed  CAS  Google Scholar 

  64. Egyhazi E and Shugar D, 5,6-Dichlororibofuranosylbenzimidazole (DRB) is phosphorylated in salivary gland cells of Chironomus tentans. FEBS Lett 107 431–435, 1979.

    Google Scholar 

  65. Egyhazi E, Ossoinak A, Holst M, Rosendahl K and Tayip U, Kinetic analysis of uptake and phosphorylation of 5,6-dichlororibofuranosylbenzimidazole (DRB) by salivary gland cells of Chironomus tentans. J. Biol. Chem. 255: 7807–7812, 1980.

    CAS  Google Scholar 

  66. Holst M and Egyhazi E, Transport and metabolism of adenosine in relation to the transcriptional activity of hnRNa genes in Chironomus salivary glands. Eur. J. Biochem 147: 631–636, 1985.

    Article  PubMed  CAS  Google Scholar 

  67. Renosto F, Seubert PA and Segel IH, Adenosine-5’-phosphosulfate kinase from Penicillium chrysogenum: Purification and kinetic characterization. J. Biol. Chem 259: 2113–2123, 1984.

    PubMed  CAS  Google Scholar 

  68. Johnson MA and Fridland A, Phosphorylation of 2’,3’-dideoxyinosine by cytosolic 5’nucleotidase of human lymphoid cells. Mol. Pharmacol 36: 291–295, 1989.

    PubMed  CAS  Google Scholar 

  69. Bondoc LL, Shannon WM, Secrist JA III, Vince R and Fridland A, Metabolism of the carbocyclic nucleoside analogue carbovir, an inhibitor of human immunodeficiency virus in human lymphoid cells. Biochemistry 29: 9839–9843, 1990.

    Article  PubMed  CAS  Google Scholar 

  70. Johnson MA, Ahluwalia G, Connelly MC, Cooney DA, Broder S, Johns DG and Fridland A, Metabolic pathways for the activation of the antiretroval agent 2’,3’-dideoxyadenosine in human lympoid cells. J. Biol. Chem 263: 15354–15357, 1988.

    PubMed  CAS  Google Scholar 

  71. Sarup JC, Johnson MA, Verhoef V and Fridland A, Regulation of purine deoxynucleoside phosphorylation by deoxycytidine kinase from human leukemic blast cells. Biochem. Pharmacol 38: 2601–2607, 1989.

    Article  PubMed  CAS  Google Scholar 

  72. Bennett Jr LL, Shealy YF, Allan PW, Rose LM, Shannon WM and Arnett G, Phosphorylation of the carbocyclic analog of 2’-deoxyguanosine in cells infected with herpes viruses. Biochem. Pharmacol 40: 1515–1522, 1990.

    Article  PubMed  CAS  Google Scholar 

  73. Jurovcik M and Holy A, Metabolism of pyrimidine L-nucleosides. Nucleic Acids Res. 3: 2143–2154, 1976.

    Article  PubMed  CAS  Google Scholar 

  74. Wang CC and Cheng HW, The doexyribonucleoside phosphotransferase of Trichomonas vaginales: A potential target for anti-trichomonial chemotherapy. J. Exp. Med 160: 987–1000, 1984.

    Article  PubMed  CAS  Google Scholar 

  75. Tan CK, Civil R, Mian AM, So AG and Downey KM, Inhibition of the RNase H activity of HIV reverse transcriptase by azidothymidylate. Biochemistry 30: 4831–4836, 1991.

    Article  PubMed  CAS  Google Scholar 

  76. Harrington JA, Miller WH and Spector T, Effector studies of 3’-azidothymidine nucleotides with human ribonucleotide reductase. Biochem. Pharmacol 36: 3757–3761, 1987.

    Article  PubMed  CAS  Google Scholar 

  77. Dzik JM, Bremer M, Kulikowski T, Ciegla J, Ciegla JM, Rode W and Shugar D, Interaction of the 5’-phosphate of the anti-HIV agent 3’-azido-3’-deoxythymidine and 3’-azido-2’,3’dideoxyuridine with thymidylate synthase. Biochem. Biophys. Res. Commun 155: 1418–1423, 1988.

    Article  PubMed  CAS  Google Scholar 

  78. Stein JM, Stoeckler JD, Li S-Y, Tolman RL, MacCoss M, Chen A, Karkas JD, Ashton WT and Parks Jr RE, Inhibition of human nucleosides and nucleotides. Biochem. Pharmacol 36: 1237–1244, 1987.

    Article  PubMed  CAS  Google Scholar 

  79. Bzowska A, Kulikowska E, Shugar D, Bing-yi C, Lindborg B and Johansson NG, Acyclonucleoside analogue inhibitors of mammalian purine nucleoside phosphorylase. Biochem. Pharmacol 41: 1791–1803, 1991.

    Article  PubMed  CAS  Google Scholar 

  80. Tuttle JV and Krenitsky TA, Effects of acyclovir and its metabolites on purine nucleoside phosphorylase. J. Biol. Chem 259: 4065–4069, 1984.

    PubMed  CAS  Google Scholar 

  81. Heinemann V, Xu Y-Z, Chubb S, Sen A, Hertel LW, Grindey GB and Plunkett W, Inhibition of ribonucleotide reduction in CCRF-CEM cells by 2’,2’-difluorodeoxycytidine. Mol. Pharmacol 38: 567–572, 1990.

    PubMed  CAS  Google Scholar 

  82. Parker WB, Shadix SC, Chang C-H, White EL, Rose LM, Brockman RW, Shortnacy AT, Montgomery JA, Secrist III JA and Bennett Jr LL, Effects of 2-chloro-9-(2-fluoro)-oarabinofuranosyl)adenine on K562 cellular metabolism and the inhibition of human ribonucleotide reductase and DNA polymerases by its 5’-triphosphate. Cancer Res. 51: 2386–2394, 1991.

    PubMed  CAS  Google Scholar 

  83. Shimada N, Hasegawa S, Harada T, Tomisawa T, Fuji A and Takita T, Oxetanocin, a novel nucleoside from bacteria. J. Antibiotics (Tokyo) 39: 1623–1625, 1986.

    Article  CAS  Google Scholar 

  84. Shimada N, Hasegawa S, Saito S, Nishikjori T, Fujii A and Takita T, Derivatives of oxetanocin: Oxetanocins H, X and G, and 2-aminooxetanocin A..1. Antibiotics (Tokyo) 11: 1788–1790, 1987.

    Article  Google Scholar 

  85. Nishiyama Y, Yamamato N, Takahashi K and Shimada N, Selective inhibition of human cytomegalovirus by a novel nucleoside, oxetanocin G. Antimicrob. Agents Chemother 32: 1053–1056, 1988.

    Article  PubMed  CAS  Google Scholar 

  86. Tseng CK-H, Marquez VE, Milne GWA, Wysocki RJJr, Misuya H, Shirasaki T and Driscoll JS, A ring-enlarged oxetanocin A analogue as an inhibitor of HIV infectivity. J. Med. Chem 34: 343–349, 1991.

    Article  PubMed  CAS  Google Scholar 

  87. Daikoku T, Yamamoto N, Saito S, Kitagawa M, Shimada N and Nishiyama Y, Mechanism of inhibition of human cytomegalovirus replication by oxetanocin G. Biochem. Biophys. Res. Commun 176: 805–812, 1991.

    Article  PubMed  CAS  Google Scholar 

  88. Kohlbrenner WE, Carter CD, Fesik SW, Norbeck DW and Erickson J, Efficiency of phosphorylation of the cyclobut-G (A-69992) enantiomers by HSV-1 thymidine kinase does not correlate with their anti-herpesvirus activity. Biochem. Pharmacol 40: R5–R10, 1990.

    Article  PubMed  CAS  Google Scholar 

  89. Bisacchi GS, Braitman A, Cianci CW, Clark JM, Field AK, Hagen ME, Hockstein DR, Malley MF, Mitt T, Slusarchyk WA, Sundeen JE, Terry BJ, Tuomari AV, Weaver ER, Young MG and Zahler R, Synthesis and antiviral activity of enantiomeric forms of cyclobutyl nucleoside analogues. J. Med. Chem 34: 1415–1421, 1991.

    Article  PubMed  CAS  Google Scholar 

  90. Bamford MJ, Coe PL and Walker RT, Synthesis and antiviral activity of 3’-deoxy-3’-Chydroxymethyl nucleosides. J. Med. Chem 33: 2494–2501, 1990.

    Article  PubMed  CAS  Google Scholar 

  91. Acton EM, Goerner RN, Uh HS, Ryan KJ and Henry DW, Improved antitumour effects in 3’-branched homologues of 2’-deoxythioguanosine: synthesis and evaluation of thioguanine nucleosides of 2,3-dideoxy-3-(hydroxymethyl)-n-erythro-pentofuranose. J. Med. Chem 22: 518–525, 1979.

    Article  PubMed  CAS  Google Scholar 

  92. Shugar D, New antiviral agents: some recent developments. In: Medicinal Chemistry Advances (De Las Heras FG and Vega S, eds), pp. 225–238, Pergamon Press, Oxford, 1981.

    Google Scholar 

  93. Shugar D, Antiviral agents —some current developments. Pure Appl. Chem 57: 423–440, 1985.

    Article  CAS  Google Scholar 

  94. Shugar D, Progress with antiviral agents. FEBS Lett. 40 (Suppl.): S48–S62, 1974.

    Article  PubMed  Google Scholar 

  95. Nakai Y and LePage GA, Characterization of the kinases involved in the phosphorylation of a-and (3–2’-deoxythioguanosine. Cancer Res. 32: 2245–2451, 1972.

    Google Scholar 

  96. LePage GA, Banks PA, Noujaim MJ and Buzzell GR, In vivo effects in mice produced by a 3’-branched homologue of a-2’-deoxythioguanosine. Cancer Chemother. Pharmacol 5: 127–131, 1980.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Biochemistry & Biophysics, Polish Academy of Sciences, 36 Rakowiecka St., 02-532, Warszawa, Poland

    D. Shugar

  2. Department of Biophysics, Institute of Experimental Physics, University of Warsaw, 93 Zwirki Wigury St., 02-089, Warszawa, Poland

    D. Shugar

Authors
  1. D. Shugar
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Polish Academy of Sciences, University of Warsaw, Warsaw, Poland

    David Shugar

  2. Institute of Biochemistry & Biophysics, Polish Academy of Science, 36 Rakowiecka St., 02-532, Warszawa, Poland

    David Shugar

  3. Department of Biophysics, Institute of Experimental Physics, University of Warsaw, 93 Żwirki i Wigury St., 02-089, Warszawa, Poland

    David Shugar

  4. Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteura St., 02-093, Warszawa, Poland

    Wojciech Rode

  5. Department of Pharmaceutical Technology & Biochemistry, Technical University of Gdańsk, 80-952, Gdańsk, Poland

    Edward Borowski

Rights and permissions

Reprints and permissions

Copyright information

© 1992 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Shugar, D. (1992). Phosphorylating Enzymes Involved in Activation of Chemotherapeutic Nucleosides and Nucleotides. In: Shugar, D., Rode, W., Borowski, E. (eds) Molecular Aspects of Chemotherapy. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-02740-0_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-02740-0_17

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-02742-4

  • Online ISBN: 978-3-662-02740-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation