Inhibition of reverse transcriptase from feline immunodeficiency virus by analogs of 2′-deoxyadenosine-5′-triphosphate

Richard C. Cronn, Kathryn Martin Remington, Bradley D. Preston, Thomas W. North

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Abstract

The replication of feline immunodeficiency virus (FIV) in cultured cells was inhibited by 2′,3′-dideoxyadenosine (ddA) and by 9-(2-phosphonylmethoxyethyI)adenine (PMEA) with IC50 values of 0.98 and 0.95 μM, respectively. The effects of the presumed active forms of these inhibitors, ddATP and PMEA-diphosphate (PMEApp), upon the FIV reverse transcriptase (RT) were examined with two different template-primer systems. Both of these compounds were potent inhibitors of the FIV RT in reactions with primed φX-174 DNA, yielding Ki values of 8.8 nM for ddATP and 5.0 nM for PMEApp. However, they were both poor inhibitors of the reaction with poly(rU)-oligo(dA); concentrations of ddATP or PMEApp greater than 10 μM were required to inhibit this reaction by 50%. Further analysis of the reaction with poly(rU)-oligo(dA) revealed that even in the absence of inhibitors the primers were extended by less than 20 nucleotides. In contrast, high molecular weight products were obtained in reactions with φX-174 DNA. These results suggest that the reaction of FIV RT with poly(rU)-oligo(dA) is not highly processive. The high degree of termination encountered during this reaction with poly(rU)-oligo(dA) may be responsible for the low inhibitory potential of ddATP and PMEApp.

Original languageEnglish (US)
Pages (from-to)1375-1381
Number of pages7
JournalBiochemical Pharmacology
Volume44
Issue number7
DOIs
StatePublished - Oct 6 1992
Externally publishedYes

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Feline Immunodeficiency Virus
RNA-Directed DNA Polymerase
Viruses
Adenine
Dideoxyadenosine
Diphosphates
DNA
Inhibitory Concentration 50
Cultured Cells
Nucleotides
Molecular Weight
Molecular weight
Cells
2',3'-dideoxyadenosine triphosphate
oligo(dA)-poly(rU)
9-(2-(phosphonomethoxy)ethyl)adenine diphosphate
2'-deoxyadenosine triphosphate

ASJC Scopus subject areas

  • Pharmacology

Cite this

Inhibition of reverse transcriptase from feline immunodeficiency virus by analogs of 2′-deoxyadenosine-5′-triphosphate. / Cronn, Richard C.; Remington, Kathryn Martin; Preston, Bradley D.; North, Thomas W.

In: Biochemical Pharmacology, Vol. 44, No. 7, 06.10.1992, p. 1375-1381.

Research output: Contribution to journalArticle

Cronn, Richard C. ; Remington, Kathryn Martin ; Preston, Bradley D. ; North, Thomas W. / Inhibition of reverse transcriptase from feline immunodeficiency virus by analogs of 2′-deoxyadenosine-5′-triphosphate. In: Biochemical Pharmacology. 1992 ; Vol. 44, No. 7. pp. 1375-1381.
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