The enzymatic synthesis of nucleoside analogues
O'Connell, Grace Josephine (1994) The enzymatic synthesis of nucleoside analogues. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b1418035~S9
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. 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. 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.
|Item Type:||Thesis or Dissertation (PhD)|
|Subjects:||Q Science > QP Physiology|
|Library of Congress Subject Headings (LCSH):||Ribavirin -- Research, Nucleosides -- Research, Antiviral agents -- Research, Influenza -- Research|
|Institution:||University of Warwick|
|Theses Department:||Department of Chemistry|
|Supervisor(s)/Advisor:||Hutchinson, D. W. (David Wesley) ; Crout, D. H. G. ; Challand, Richard, 1946- ; Slater, M. (Martin)|
|Sponsors:||Wellcome Foundation Ltd. (Wellcome)|
|Format of File:|
|Extent:||219 leaves : ill., charts|
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