Substrate specificity of Escherichia coli thymidine phosphorylase for pyrimidine nucleosides with anti-human immunodeficiency virus activity

Biochem Pharmacol. 1992 Jul 22;44(2):199-204. doi: 10.1016/0006-2952(92)90001-y.

Abstract

Various nucleoside antiviral agents and their metabolites were examined for their ability to be cleaved across the glycosidic bond by Escherichia coli thymidine phosphorylase. The increasing order of susceptibility to cleavage was U greater than T much greater than C derivatives. Nucleosides that were unsaturated in the sugar moiety were more susceptible than saturated ones. 3'-Deoxy-2',3'-didehydrothymidine was a substrate, whereas 3'-azido-, 3'-fluoro-, 3'-oxo- and 3'-thiapyrimidine nucleosides were resistant to this enzyme.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiviral Agents / metabolism*
  • Biological Availability
  • Deoxyuridine / analogs & derivatives
  • Deoxyuridine / metabolism
  • Dideoxynucleosides / metabolism
  • Emtricitabine / analogs & derivatives
  • Escherichia coli / enzymology*
  • HIV / drug effects
  • Pyrimidine Nucleosides / metabolism*
  • Stavudine
  • Substrate Specificity
  • Thymidine Phosphorylase / metabolism*
  • Zalcitabine / analogs & derivatives
  • Zalcitabine / metabolism

Substances

  • Antiviral Agents
  • Dideoxynucleosides
  • Pyrimidine Nucleosides
  • 2',3'-dideoxy-5-fluoro-3'-thiauridine
  • Zalcitabine
  • Stavudine
  • Thymidine Phosphorylase
  • Emtricitabine
  • Racivir
  • Deoxyuridine