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The enzymatic synthesis of nucleoside analogues

By Grace Josephine O'Connell

Abstract

Ribavirin, 1--D-ribofuranosyl-1,2,4-triazole-3-carboxamide, is a broad spectrum antiviral agent active against both DNA and RNA viruses. A range of 1,2,3-triazole, 1,2,4-triazole and benzotriazole analogues of ribavirin was synthesised using a crude extract of N-deoxyribosyltransferases from Lactobacillus leichmannii in the chemoenzymatic synthesis of nucleoside analogues with potential antiviral activity. N-Deoxyribosyltransferase catalyses the transfer of the 2-deoxyribose sugar between purine and pyrimidine bases. Of thirty two bases synthesised, twelve were found to act as acceptors in the N-deoxyribosyltransferase reaction. Nine 2'-deoxyribofuranosyl-1,2,4-triazole nucleoside analogues were isolated and characterised. Only one nucleoside showed any significant antiviral activity.\ud \ud 2'-Deoxyribavirin was found to possess antiviral activity against the influenza virus. Attempts were made to synthesise the nucleoside chemical from ribavirin on a larger scale, but without success. However, 5'-iodo-5'-deoxyribavirin and 5'-deoxyribavirin were synthesised, the former showing slight antiviral activity.\ud \ud The specificities of the N-deoxyribosyltransferases for purine, pyrimidine and triazole bases are discussed, gathering together the findings of previous workers with the results presented in this thesis

Topics: QP
OAI identifier: oai:wrap.warwick.ac.uk:2950

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Citations

  1. (1984). 1,2,3-Triazoles and their benzo derivatives, in Comprehensive Heterocyclic Chemistry, doi
  2. 1,2,3, Triazoles, doi
  3. (1976). Acta Cryst., doi
  4. (1981). Agents Chemother., doi
  5. (1976). Amino Acid Nucleic Acid,
  6. (1979). Analogues of Ribavirin,
  7. (1983). Antimicrob. Agents Chemother., doi
  8. Antiviral Agents, doi
  9. (1991). Antiviral Chem. doi
  10. (1988). Antiviral chemotherapy: An introduction and reasons for the slow progress, particularly towards rational design., doi
  11. (1974). Chemical syntheses and transformations of nucleosides, doi
  12. (1990). Chemical synthesis, in Nucleic acids in chemistry and biology, doi
  13. (1979). Chemical transformations of the sugar moiety of nucleosides, doi
  14. (1979). Chemistry of naturally occurring pyrimidine nucleosides and analogues, doi
  15. (1979). Chemistry of the heterocyclic moiety of purine nucleosides and some closely related analogues, doi
  16. (1985). Clercq, Antimicrob. Agents Chemother., doi
  17. Design of nucleoside analogues as potential antiviral agents, doi
  18. (1993). Enzyme Microb. doi
  19. (1986). Enzymes as catalysts in organic synthesis, doi
  20. (1985). Handbook of Heterocyclic Chemistry, doi
  21. (1992). John-Wiley and Sons Inc., doi
  22. (1965). Latvijas PSR Zinatnu Akad.
  23. (1973). NMR spectroscopy in the study of nucleic acid components and certain related derivatives,
  24. (1978). Nucleoside deoxyribosyltransferase from Lactobacillus helveticus, in Methods doi
  25. (1979). Nucleosides, in Comprehensive organic chemistry,
  26. (1973). Oxidation of a secondary hydroxyl group of the sugar moiety of a nucleoside,
  27. Patent Appl.,
  28. Perkin Trans. doi
  29. (1978). Practice of Thin Layer doi
  30. (1992). Protective group strategies in the synthesis of functionalized carbohydrates,
  31. (1991). Protective groups in organic synthesis, 2nd edition, doi
  32. (1988). Purification of laboratory chemicals, 3rd edition, doi
  33. Regular, nonsporing gram-positive rods, in Bergey's manual of systematic bacteriology,
  34. (1980). Ribavirin: A Broad Spectrum Antiviral Agent, doi
  35. (1980). Ribavirin: Structure and Antiviral Activity Relationships, in Ribavirin: A Broad Spectrum Antiviral Agent, doi
  36. Safety evaluation of the broad-spectrum antiviral agent ribavirin
  37. Shoyu Co.,
  38. (1980). The Preclinical Toxicology and Safety of Ribavirin, in Ribivirin: A Broad Spectrum Antiviral Agent,
  39. (1970). The Pyrimidines, The Chemistry of Heterocyclic Compounds, doi
  40. (1969). Thin Layer Chromatography, A Laboratory Notebook, doi

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