Cellular pharmacology and anti-HIV activity of 2',3'-dideoxyguanosine

M. E. Busso, L. Resnick, B. H. Yang, A. M. Mian

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The antiviral activity, uptake, and metabolism of 2',3'-dideoxyguanosine was investigated in human immunodeficiency virus- (HIV) infected and noninfected human cells. 2',3'-Dideoxyguanosine had anti-HIV activity (effective dose 50%: 0.1-1.0 μM) in H-9 and MT-2 cells. The addition of excess (≥ 30 μM) guanosine, deoxyguanosine, or 8-aminoguanosine had no effect on the anti-HIV activity of 2',3'-dideoxyguanosine. In [8-3H]2',3'-dideoxyguanosine-exposed cells, the intracellular radioactivity was twofold higher than the extracellular. When guanosine, deoxyguanosine, or 8-aminoguanosine was preincubated or added simultaneously to 2',3'-dideoxyguanosine, uptake of 2',3'-dideoxyguanosine was reduced by 28 to 34%, whereas addition of p-nitrobenzylmercaptopurine riboside (20 μM) had no effect. In metabolism studies using H-9 cells, dideoxyguanosine triphosphate could not be detected despite a 24-h incubation of 2',3'-dideoxyguanosine at effective anti-HIV concentrations. The addition of excess (≥ 30 μM) guanosine, deoxyguanosine, and 8-aminoguanosine, while inhibiting the catabolism of 2',3'-dideoxyguanosine, did not enhance the anabolic conversion of 2',3'-dideoxyguanosine to dideoxyguanosine triphosphate. Our failure to detect the formation of dideoxyguanosine triphosphate and the lack of reversal of antiviral effects by natural purine nucleosides raises questions on the role of this metabolite in the anti-HIV activity of 2',3'-dideoxyguanosine.

Original languageEnglish
Pages (from-to)1139-1146
Number of pages8
JournalAIDS Research and Human Retroviruses
Volume6
Issue number9
StatePublished - Jan 1 1990
Externally publishedYes

Fingerprint

HIV-2
Pharmacology
Deoxyguanosine
Guanosine
HIV
Antiviral Agents
Purine Nucleosides
2',3'-dideoxyguanosine
Radioactivity

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Busso, M. E., Resnick, L., Yang, B. H., & Mian, A. M. (1990). Cellular pharmacology and anti-HIV activity of 2',3'-dideoxyguanosine. AIDS Research and Human Retroviruses, 6(9), 1139-1146.

Cellular pharmacology and anti-HIV activity of 2',3'-dideoxyguanosine. / Busso, M. E.; Resnick, L.; Yang, B. H.; Mian, A. M.

In: AIDS Research and Human Retroviruses, Vol. 6, No. 9, 01.01.1990, p. 1139-1146.

Research output: Contribution to journalArticle

Busso, ME, Resnick, L, Yang, BH & Mian, AM 1990, 'Cellular pharmacology and anti-HIV activity of 2',3'-dideoxyguanosine', AIDS Research and Human Retroviruses, vol. 6, no. 9, pp. 1139-1146.
Busso, M. E. ; Resnick, L. ; Yang, B. H. ; Mian, A. M. / Cellular pharmacology and anti-HIV activity of 2',3'-dideoxyguanosine. In: AIDS Research and Human Retroviruses. 1990 ; Vol. 6, No. 9. pp. 1139-1146.
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