Skip to main content

Enzymatic formation of potential anticancer and antiviral inosine analogues

Experientia volume 52, pages 878–881 (1996)Cite this article

Abstract

Theoretically, inosine analogues should act as effective inhibitors of tumor cell proliferation and viral replication. To acquire a broad spectrum of new candidate inosine analogues, a rapid, facile, quantitative and stereoselective method for deaminating potential antitumor and antiviral adenine analogues previously synthesized in our laboratory was developed. A novel 5′-adenylic acid deaminase, with relaxed substrate requirements, fromAspergillus species was utilized to deaminate four hexofuranosyladenine nucleosides and five adenine nucleoside dialdehydes to their corresponding inosine analogues. The fastest rates of deamination for the hexofuranosyl nucleosides were for the compounds where the vicinal hydroxyl groups on the sugars are oriented in the erythro configuration. For rapid deamination of the adenine nucleoside dialdehydes, theR configuration at the proximal carbon atom is preferred, while the nature of the group on the distal carbon atom has no significant effect on the rate or extent of deamination.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Literatur

  1. Bessman M. J., Lehman I. R., Adler J., Zimmerman S. B., Simms E. S. and Kornberg A. (1958) Enzymatic synthesis of deoxyribonucleic acid. III. The incorporation of pyrimidine and purine analogues into deoxyribonucleic acid. Proc. Natl Acad. Sci. USA44: 633–640

    Google Scholar 

  2. Feix G. (1976) Primer-dependent copying of rabbit globin mRNA with Qp replicase. Nature259: 593–594

    PubMed  Google Scholar 

  3. Kahan Y-M. and Hurwitz J. (1962) The role of deoxyribonucleic acid in ribonucleic acid synthesis. IV. The incorporation of pyrimidine and purine analogues into ribonucleic acid. J. Biol. Chem.237: 3778–3785

    Google Scholar 

  4. Shapiro L. and August J. T. (1965) Replication of RNA viruses. III. Utilization of ribonucleotide analogues in the reaction catalyzed by a RNA virus polymerase. J. Mol. Biol.14: 214–220

    PubMed  Google Scholar 

  5. Miles H. T. (1961) Tautomeric forms in a polynucleotide helix and their bearing on the structure of DNA. Proc. Natl Acad. Sci. USA47: 791–802

    PubMed  Google Scholar 

  6. Lerner L. M. (1973) Interconversions of hexofuranosyl nucleosides II. Preparation of 9-α-l-idofuranosyladenine and 5′-6′-unsaturated derivatives. J. Org. Chem.37: 473–477

    Google Scholar 

  7. Lerner L. M. (1973) Interconversions of hexofuranosyl nucleosides. V. Synthesis and reexamination of the structure of 9-(6-deoxy-α-l-mannofuranosyl) adenine. J. Org. Chem.38: 3704–3709

    PubMed  Google Scholar 

  8. Lerner L. M. (1976) Adenine nucleosides derived from 6-deoxyhexofuranoses. J. Org. Chem.41: 306–310

    PubMed  Google Scholar 

  9. Lerner L. M. and Mennitt G. (1994) A new synthesis ofl-talose and preparation of its adenine nucleosides. Carbohydr. Res.259: 191–200

    Google Scholar 

  10. Lerner L. M., Sheid B. and Gaetjens E. (1987) Preparation and antileukemic screening of some new 6′-deoxyhexopyranosyladenine nucleosides. J. Med. Chem.30: 1521–1525

    PubMed  Google Scholar 

  11. Corey J. C., Mansell M. M. and Whitford T. W. Jr. (1976) Inhibition of ribonucleotide reductase activity and nucleic acid synthesis in tumor cells by the dialdehyde derivative of inosine and inosinic acid. Cancer Res.36: 3166–3170

    PubMed  Google Scholar 

  12. Cysyk R. L. and Adamson R. H. (1974) Antitumor properties and pharmacological disposition of inosine dialdehyde. Proc. Am. Assoc. Cancer Res.15: 56

    Google Scholar 

  13. Kaufman J. and Mittleman I. (1975) Clinical phase 1 trial of inosine dialdehyde (NSC 118994). Cancer Treat. Rep.59: 1007–1110

    Google Scholar 

  14. Sheid B., Saggar M., Gaetjens E. and Lerner L. M. (1991) Antiproliferative activity of purine nucleoside dialdehydes against leukemia L1210 in vitro. Cancer Chemother. Pharmacol.28: 339–343

    PubMed  Google Scholar 

  15. Jackson R. C. (1984) A kinetic model of regulation of the deoxyribonucleoside triphosphate pool composition. Pharm. Ther.24: 279–301

    Google Scholar 

  16. Srivastava V. K., Pall M. L. and Schroeder A. L. (1988) Deoxyribonucleotide triphosphate pools inNeurospora crassa: effects of histidine and hydroxyurea. Mutat. Res.200: 45–53

    PubMed  Google Scholar 

  17. Kalckar H. M. (1947) Differential spectrophotometry of purine compounds by means of specific enzymes II. Determination of adenine compounds. J. Biol. Chem.167: 445–459

    Google Scholar 

  18. Wnuk S. F., Stoeckler J. D. and Robins M. J. (1994) Nucleic acid related compounds. 82. Conversion of adenosine to inosine 5′-thioether derivatives withAspergillus oryzae adenosine deaminase or alkylnitrites. Substrate and inhibitor activities of inosine 5′-thioether derivatives with purine nucleoside phosphorylase. Nucleosides and Nucleotides13: 389–403

    Google Scholar 

  19. Grosshans J. and Wolfenden R. (1993) Transition-state discrimination by adenosine deaminase fromAspergillus oryzae. Biochim. Biophys. Acta1161: 28–32

    PubMed  Google Scholar 

  20. Wolfenden R., Sharpless T. K. and Allan R. (1967) Substrate binding by adenosine deaminase: specificity, pH dependence and competition by mercurials. J. Biol. Chem.242: 977–983

    PubMed  Google Scholar 

  21. Mitchell H. K. and McElroy W. D. (1946) Adenosine deaminase fromAspergillus oryzae. Arch. Biochem.10: 351–358

    Google Scholar 

  22. Margolin A. L., Borcherding D. R., Wolf-Kugel D. and Margolin N. (1994) AMP deaminase as a novel practical catalyst in the synthesis of 6-oxopurine ribosides and their analogues. J. Org. Chem.59: 7214–7218

    Google Scholar 

  23. Yarchoan R., Mitsuya H., Thomas R. V., Pluda J. M., Harmon N. R., Perno C-F, Marczyk K. S., Allain J. P., John D. and Broder S. (1989) In vivo activity against HIV and favorable toxicity profile of 2′-3′-dideoxyinosine. Science245: 412–415

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, SUNY, Health Science Center at Brooklyn, 450 Clarkson Ave., Box 29, 11203, Brooklyn, New York, USA

    B. Sheid

  2. Department of Pathology, SUNY, Health Science Center at Brooklyn, 450 Clarkson Ave., Box 29, 11203, Brooklyn, New York, USA

    E. Gaetjens & S. T. Chung

  3. Department of Biochemistry, SUNY Health Science Center at Brooklyn, 450 Clarkson Ave., Box 29, 11203, Brooklyn, New York, USA

    L. M. Lerner

Authors
  1. B. Sheid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Gaetjens
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. T. Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. M. Lerner
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sheid, B., Gaetjens, E., Chung, S.T. et al. Enzymatic formation of potential anticancer and antiviral inosine analogues. Experientia 52, 878–881 (1996). https://doi.org/10.1007/BF01938874

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01938874

Key words

  • Inosine analogues
  • adenine analogues
  • fungal 5′-adenylic acid deaminase