O'Connell, Grace Josephine (1994) The enzymatic synthesis of nucleoside analogues. PhD thesis, University of Warwick.

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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.

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 (PhD)
Subjects:	Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Ribavirin -- Research, Nucleosides -- Research, Antiviral agents -- Research, Influenza -- Research
Official Date:	June 1994
Dates:	Date Event June 1994 Submitted
Institution:	University of Warwick
Theses Department:	Department of Chemistry
Thesis Type:	PhD
Publication Status:	Unpublished
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:	pdf
Extent:	219 leaves : ill., charts
Language:	eng

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