Inhibition of HIV-1 replication in cultured cells with phosphorylated dideoxyuridine derivatives encapsulated in immunoliposomes

Zelphati, Olivier; Degols, Geneviève; Loughrey, Helen; Leserman, Lee; Pompon, A.; Puech, Frédéric; Maggio, A.‐F.; Imbach, Jean‐Louis; Gosselin, Gilles

doi:10.1016/0166-3542(93)90027-g

Cited by 27 publications

(6 citation statements)

References 28 publications

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“…2′,3′-Dideoxyuridine-5-triphosphate ammonium salt (pppddU) was synthesized according to [3] . NMR data were in good agreement with the literature [4] . 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) (368 mg, 1.92 mmol, 5 equiv.)…”

Section: Experimental Design Materials and Methodssupporting

confidence: 89%

Data set on the synthesis and properties of 2′,3′-dideoxyuridine triphosphate conjugated to SiO2 nanoparticles

et al. 2018

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SiO2 nanoparticles were used as a transport system for cellular delivery of phosphorylated 2′,3′-dideoxyuridine to increase its anticancer potency. This data set is related to the research article entitled “2′,3′-Dideoxyuridine triphosphate conjugated to SiO2 nanoparticles: synthesis and evaluation of antiproliferative activity” (Vasilyeva et al., 2018) [1]. It includes a protocol for the synthesis of 2′,3′-dideoxyuridine-5′-{N-[4-(prop-2-yn-1-yloxy)butyl]-γ-amino}-triphosphate, its identification by NMR, IR and ESI-MS, experimental procedure of covalent attachment to SiO2 nanoparticles with via Cu-catalyzed click-chemistry, experimental data on chemical stability of the conjugate at different pH values and cytotoxicity assessment of antiproliferative effect of the conjugate.

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Section: Experimental Design Materials and Methodssupporting

confidence: 89%

Data set on the synthesis and properties of 2′,3′-dideoxyuridine triphosphate conjugated to SiO2 nanoparticles

et al. 2018

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“…To apply the nucleosides as antiretroviral drugs, the nucleosides need to pass through the cell membrane, and to be phosphorylated by cellular kinases for generation the active triphosphates. To bypass the kinase step, liposomal-based drug delivery methods may be available to transport the 5′-triphosphate into the cell (49,50). Phosphorylated pronucleotides (masked phosphate analogues) may also useful (51,52).…”

Section: Discussionmentioning

confidence: 99%

Template properties of mutagenic cytosine analogues in reverse transcription

Suzuki¹,

Moriyama

Otsuka³

et al. 2006

Nucleic Acids Research

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We have studied the mutagenic properties of ribonucleotide analogues by reverse transcription to understand their potential as antiretroviral agents by mutagenesis of the viral genome. The templating properties of nucleotide analogues including 6-(β-D-ribofuranosyl)-3,4-dihydro-8H-pyrimido[4,5-c](1,2)oxazin-7-one, N4-hydroxycytidine, N4-methoxycytidine, N4-methylcytidine and 4-semicarbazidocytidine, which have been reported to exhibit ambiguous base pairing properties, were examined. We have synthesized RNA templates using T3 RNA polymerase, and investigated the specificity of the incorporation of deoxyribonucleoside triphosphates opposite these cytidine analogues in RNA by HIV and AMV reverse transcriptases. Except for N4-methylcytidine, both enzymes incorporated both dAMP and dGMP opposite these analogues in RNA. This indicates that they would be highly mutagenic if present in viral RNA. To study the basis of the differences among the analogues in the incorporation ratios of dAMP to dGMP, we have carried out kinetic analysis of incorporation opposite the analogues at a defined position in RNA templates. In addition, we examined whether the triphosphates of these analogues were incorporated competitively into RNA by human RNA polymerase II. Our present data supports the view that these cytidine analogues are mutagenic when incorporated into RNA, and that they may therefore be considered as candidates for antiviral agents by causing mutations to the retroviral genome.

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“…Consequently, the investigation of the SATE and DTE biolabile phosphate protections were extended to the 5'-mononucleotide of ddU. To circumvent the requirement of ddU for enzymatic activation, strategies have been designed to liberate ddUMP inside the cell using targeted liposomes (Zelphati et al, 1993) or pronucleotides (Sastry et al, 1991). Nevertheless, although comparison between different experimental systems may be difficult, it appears that the intracellular delivery of ddUMP did not correlate with the anti-HIV activity as illustrated by the .r.oderate anti-HIV-1 activity observed with the pronucleotides 4 and 5 in PBMCs (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Cytotoxicity of Mononucleoside Phosphotriester Derivatives Bearing Biolabile Phosphate Protecting Groups in Normal Human Bone Marrow Progenitor Cells

Philouze

Girardet

Lefèbvre

et al. 1996

Antivir Chem Chemother

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SummaryThe effects of three mononucleoside phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) which incorporate biolabile phosphate protecting groups, namely 5-acetyl-2-thioethyl (MeSATE), 5-(2-hydroxyethylsulfidyl)-2-thioethyl (OTE), and pivaloyloxymethyl (POM) were studied and compared to their nucleoside parent in human myeloid colony-forming cells. Moreover, the relative antiviral potency of these three pronucleotldes were determined in primary human peripheral blood mononuclear cells infected with human immunodeficiency virus type 1. The results indicate that the SATE and OTE pro-moieties, as well as their degradation products, do not induce additional toxicity. The bis(MeSATE) phosphotriester derivative of AZT emerged as the most selective inhibitor with an in-vitro therapeutic index of the same order of magnitude as observed for AZT. This study has been extended to the corresponding bis(MeSATE) and bis(OTE) phosphotriester derivatives of 2',3'-dideoxyuridine (ddU).

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Inhibition of HIV-1 replication in cultured cells with phosphorylated dideoxyuridine derivatives encapsulated in immunoliposomes

Cited by 27 publications

References 28 publications

Data set on the synthesis and properties of 2′,3′-dideoxyuridine triphosphate conjugated to SiO2 nanoparticles

Data set on the synthesis and properties of 2′,3′-dideoxyuridine triphosphate conjugated to SiO2 nanoparticles

Template properties of mutagenic cytosine analogues in reverse transcription

Comparison of Cytotoxicity of Mononucleoside Phosphotriester Derivatives Bearing Biolabile Phosphate Protecting Groups in Normal Human Bone Marrow Progenitor Cells

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