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Antiviral Agents

Glycine-Amide Is an Active Metabolite of the Antiretroviral Tripeptide Glycyl-Prolyl-Glycine-Amide

Elin Andersson, Peter Horal, Alenka Jejcic, Stefan Höglund, Jan Balzarini, Anders Vahlne, Bo Svennerholm
Elin Andersson
Department of Clinical Virology, University of Göteborg, Göteborg
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  • For correspondence: elin.andersson@microbio.gu.se anders.vahlne@labmed.ki.se
Peter Horal
Department of Clinical Virology, University of Göteborg, Göteborg
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Alenka Jejcic
Division of Clinical Virology, Karolinska Institutet, Stockholm
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Stefan Höglund
Department of Biochemistry, Biomedical Center, Uppsala University, Uppsala, Sweden
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Jan Balzarini
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
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Anders Vahlne
Division of Clinical Virology, Karolinska Institutet, Stockholm
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  • For correspondence: elin.andersson@microbio.gu.se anders.vahlne@labmed.ki.se
Bo Svennerholm
Department of Clinical Virology, University of Göteborg, Göteborg
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DOI: 10.1128/AAC.49.1.40-44.2005
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    FIG. 1.

    Effect of the metabolites and GPG-NH2 on HIV-1 replication. Each test compound was added to HIV-1-infected H9 cells at 100 μM, and the level of production of p24 was measured. The data represent mean values and standard deviations for three to four samples.

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    FIG. 2.

    Production of p24 plotted against escalating drug concentration after treatment of HIV-1IIIB-infected H9 cells with G-NH2 or GPG-NH2. The IC50s were 3.2 μM for G-NH2 and 11 μM for GPG-NH2.

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    FIG. 3.

    Effects of treatment with GPG-NH2, G-NH2, G-OH, or cyclosporine (1 μg/ml) on the proliferation of PHA-stimulated PBMCs after 4 days. Incorporation of [3H]thymidine was measured in a β-scintillation counter and plotted (as a percentage of the thymidine incorporation for the control) against the drug concentration. The data represent mean values and standard deviations for three to four tests (n = 6).

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    FIG. 4.

    Morphological studies of HIV-1 virions produced from untreated or G-NH2-treated cells and analyzed with TEM. (a) Wild-type HIV-1 showing characteristic dense, cone-shaped core (left) and round, centrally placed tangential sections (middle and right); (b) HIV-1 treated with 100 μM G-NH2 showing empty, multiple core structures (right); (c) HIV-1 treated with 100 μM G-NH2 showing a double core (left and above) and distorted core structure (right); (d) HIV-1 treated with 100 μM G-NH2 showing an elongated core in an enlarged virus envelope (below), a hollow core (left above), and a double core structure (right). Bars, 100 nm.

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  • TABLE 1.

    Sensitivities of HIV-1 strains to GPG-NH2 and G-NH2

    HIV-1 strainIC50 (μM [range])
    GPG-NH2G-NH2
    IIIB16a (7.4-21)11a (3.2-22)
    Clinical isolatesb14 (2.7-24)23 (14-41)
    • ↵a The IC50s are averages of six tests.

    • ↵b Seven clinical isolates were tested.

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Glycine-Amide Is an Active Metabolite of the Antiretroviral Tripeptide Glycyl-Prolyl-Glycine-Amide
Elin Andersson, Peter Horal, Alenka Jejcic, Stefan Höglund, Jan Balzarini, Anders Vahlne, Bo Svennerholm
Antimicrobial Agents and Chemotherapy Dec 2004, 49 (1) 40-44; DOI: 10.1128/AAC.49.1.40-44.2005

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Glycine-Amide Is an Active Metabolite of the Antiretroviral Tripeptide Glycyl-Prolyl-Glycine-Amide
Elin Andersson, Peter Horal, Alenka Jejcic, Stefan Höglund, Jan Balzarini, Anders Vahlne, Bo Svennerholm
Antimicrobial Agents and Chemotherapy Dec 2004, 49 (1) 40-44; DOI: 10.1128/AAC.49.1.40-44.2005
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