Biochemical genetic analysis of formycin B action in Leishmania donovani

N. Robinson, K. Kaur, K. Emmett, D. M. Iovannisci, B. Ullman

Research output: Contribution to journalArticle

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Abstract

Formycin B is cytotoxic toward Leishmania and is a potential chemotherapeutic agent for leishmaniasis. In order to determine the mechanism of action of formycin B, we have isolated and characterized clonal populations of formycin B-resistant Leishmania donovani. These formycin B-resistant clones are also cross-resistant to formycin A and allopurinol riboside-mediated growth inhibition. Incubation of the formycin B-resistant cells with [3H]formycin B indicates that, unlike wild type cells, the resistant populations cannot accumulate phosphorylated metabolites of exogenous [3H]formycin B. This is due to a defective transport system for formycin B in the resistant cells. However, wild type and mutant cells incorporate [3H]formycin A equally efficiently into [3H]formycin A-containing nucleotides and into RNA. These data suggest that formycin B cytotoxicity in Leishmania is not mediated by its incorporation as the adenosine analog into RNA. A plausible alternative hypothesis is proposed for the mechanism of action of the pyrazolo(4,3-d)pyrimidine C-nucleosides based upon depletion of an essential intracellular metabolite.

Original languageEnglish (US)
Pages (from-to)7637-7643
Number of pages7
JournalJournal of Biological Chemistry
Volume259
Issue number12
StatePublished - 1984

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Leishmania donovani
Molecular Biology
Leishmania
Metabolites
Pyrimidine Nucleosides
RNA
formycin B
Dilatation and Curettage
Leishmaniasis
Cytotoxicity
Nucleosides
Adenosine
Population
Nucleotides
Clone Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Robinson, N., Kaur, K., Emmett, K., Iovannisci, D. M., & Ullman, B. (1984). Biochemical genetic analysis of formycin B action in Leishmania donovani. Journal of Biological Chemistry, 259(12), 7637-7643.

Biochemical genetic analysis of formycin B action in Leishmania donovani. / Robinson, N.; Kaur, K.; Emmett, K.; Iovannisci, D. M.; Ullman, B.

In: Journal of Biological Chemistry, Vol. 259, No. 12, 1984, p. 7637-7643.

Research output: Contribution to journalArticle

Robinson, N, Kaur, K, Emmett, K, Iovannisci, DM & Ullman, B 1984, 'Biochemical genetic analysis of formycin B action in Leishmania donovani', Journal of Biological Chemistry, vol. 259, no. 12, pp. 7637-7643.
Robinson N, Kaur K, Emmett K, Iovannisci DM, Ullman B. Biochemical genetic analysis of formycin B action in Leishmania donovani. Journal of Biological Chemistry. 1984;259(12):7637-7643.
Robinson, N. ; Kaur, K. ; Emmett, K. ; Iovannisci, D. M. ; Ullman, B. / Biochemical genetic analysis of formycin B action in Leishmania donovani. In: Journal of Biological Chemistry. 1984 ; Vol. 259, No. 12. pp. 7637-7643.
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