Inhibition of HIV proliferation in MT-4 cells by antisense oligonucleotide conjugated to lipophilic groups
Identifieur interne : 004570 ( Main/Exploration ); précédent : 004569; suivant : 004571Inhibition of HIV proliferation in MT-4 cells by antisense oligonucleotide conjugated to lipophilic groups
Auteurs : F. P. Svinarchuk [Russie] ; D. A. Konevetz [Russie] ; O. A. Pliasunova [Russie] ; A. G. Pokrovsky [Russie] ; V. V. Vlassov [Russie]Source :
- Biochimie [ 0300-9084 ] ; 1993.
English descriptors
- Teeft :
- Antisense, Antisense oligonucleotide derivatives, Antisense oligonucleotides, Antivirai activity, Antiviral, Antiviral activity, Assay, Cell culture, Cell lysate, Cell viability, Cellular esterases, Cholesterol derivatives, Cholesteryl, Conjugation, Control oligonucleotide, Control virus sample, Culture medium, Cultured cells, Derivative, Electrophoretic mobility, Ester bond, Experimental sample, Febs lett, Final concentration, Gene expression, Human immunodeficiency virus, Immunodeficiency, Inverse value, Linker structure, Lipophilic, Lipophilic anchor, Lipophilic groups, Monopalmitoyl propylene diamine hydrochloride, Oligonucleotide, Oligonucleotide derivatives, Oligonucleotides, Optical density, Parent oligonucleotide, Parent oligonucleotides, Proc natl acad, Propylene diamine, Reaction mixture, Single experiment, Test compound, Transcriptase activity, Viral.
Abstract
Abstract: Anti-HIV activity of antisense oligonucleotide derivatives conjugated to lipophilic groups has been investigated. Aliphatic linear structures and cholesterol were coupled to the 5′-terminal phosphate of oligonucleotides via glycin or propylene diamine spacers. The oligonucleotides were targeted to a conserved sequence of the viral gene env, to a sequence in the negative sense viral RNA, to the 5′-terminus of the gene rev and to poly(A) sequences. The conjugation with lipophilic groups stimulated binding of oligonucleotides to cells and protected the oligonucleotides against cellular nucleases. The lipophilic derivatives of oligonucleotides containing an ester bond in the linker structure were cleaved by cellular esterases yielding oligonucleotides protected from 5′-nuclease degradation by the glycin residue. Antiviral activity of the derivatives exceeded that of the corresponding unmodified oligonucleotides. The virus suppression was sequence-specific and most pronounced in the case of the cholesteryl conjugated oligonucleotides.
Url:
DOI: 10.1016/0300-9084(93)90024-M
Affiliations:
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Konevetz</name><affiliation wicri:level="1"><country xml:lang="fr">Russie</country><wicri:regionArea>Institute of Bioorganic Chemistry, Institute of Molecular Biology, Koltsovo, Novosibirsk Region Institute of Biochemistry, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk</wicri:regionArea><wicri:noRegion>Novosibirsk</wicri:noRegion></affiliation></author><author><name sortKey="Pliasunova, O A" sort="Pliasunova, O A" uniqKey="Pliasunova O" first="O. A." last="Pliasunova">O. A. Pliasunova</name><affiliation wicri:level="1"><country xml:lang="fr">Russie</country><wicri:regionArea>Institute of Bioorganic Chemistry, Institute of Molecular Biology, Koltsovo, Novosibirsk Region Institute of Biochemistry, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk</wicri:regionArea><wicri:noRegion>Novosibirsk</wicri:noRegion></affiliation></author><author><name sortKey="Pokrovsky, A G" sort="Pokrovsky, A G" uniqKey="Pokrovsky A" first="A. 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Vlassov</name><affiliation wicri:level="1"><country xml:lang="fr">Russie</country><wicri:regionArea>Institute of Bioorganic Chemistry, Institute of Molecular Biology, Koltsovo, Novosibirsk Region Institute of Biochemistry, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk</wicri:regionArea><wicri:noRegion>Novosibirsk</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Biochimie</title><title level="j" type="abbrev">BIOCHI</title><idno type="ISSN">0300-9084</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1993">1993</date><biblScope unit="volume">75</biblScope><biblScope unit="issue">1–2</biblScope><biblScope unit="page" from="49">49</biblScope><biblScope unit="page" to="54">54</biblScope></imprint><idno type="ISSN">0300-9084</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0300-9084</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Antisense</term><term>Antisense oligonucleotide derivatives</term><term>Antisense oligonucleotides</term><term>Antivirai activity</term><term>Antiviral</term><term>Antiviral activity</term><term>Assay</term><term>Cell culture</term><term>Cell lysate</term><term>Cell viability</term><term>Cellular esterases</term><term>Cholesterol derivatives</term><term>Cholesteryl</term><term>Conjugation</term><term>Control oligonucleotide</term><term>Control virus sample</term><term>Culture medium</term><term>Cultured cells</term><term>Derivative</term><term>Electrophoretic mobility</term><term>Ester bond</term><term>Experimental sample</term><term>Febs lett</term><term>Final concentration</term><term>Gene expression</term><term>Human immunodeficiency virus</term><term>Immunodeficiency</term><term>Inverse value</term><term>Linker structure</term><term>Lipophilic</term><term>Lipophilic anchor</term><term>Lipophilic groups</term><term>Monopalmitoyl propylene diamine hydrochloride</term><term>Oligonucleotide</term><term>Oligonucleotide derivatives</term><term>Oligonucleotides</term><term>Optical density</term><term>Parent oligonucleotide</term><term>Parent oligonucleotides</term><term>Proc natl acad</term><term>Propylene diamine</term><term>Reaction mixture</term><term>Single experiment</term><term>Test compound</term><term>Transcriptase activity</term><term>Viral</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Anti-HIV activity of antisense oligonucleotide derivatives conjugated to lipophilic groups has been investigated. Aliphatic linear structures and cholesterol were coupled to the 5′-terminal phosphate of oligonucleotides via glycin or propylene diamine spacers. The oligonucleotides were targeted to a conserved sequence of the viral gene env, to a sequence in the negative sense viral RNA, to the 5′-terminus of the gene rev and to poly(A) sequences. The conjugation with lipophilic groups stimulated binding of oligonucleotides to cells and protected the oligonucleotides against cellular nucleases. The lipophilic derivatives of oligonucleotides containing an ester bond in the linker structure were cleaved by cellular esterases yielding oligonucleotides protected from 5′-nuclease degradation by the glycin residue. Antiviral activity of the derivatives exceeded that of the corresponding unmodified oligonucleotides. The virus suppression was sequence-specific and most pronounced in the case of the cholesteryl conjugated oligonucleotides.</div></front></TEI><affiliations><list><country><li>Russie</li></country></list><tree><country name="Russie"><noRegion><name sortKey="Svinarchuk, F P" sort="Svinarchuk, F P" uniqKey="Svinarchuk F" first="F. P." last="Svinarchuk">F. P. Svinarchuk</name></noRegion><name sortKey="Konevetz, D A" sort="Konevetz, D A" uniqKey="Konevetz D" first="D. A." last="Konevetz">D. A. Konevetz</name><name sortKey="Pliasunova, O A" sort="Pliasunova, O A" uniqKey="Pliasunova O" first="O. A." last="Pliasunova">O. A. Pliasunova</name><name sortKey="Pokrovsky, A G" sort="Pokrovsky, A G" uniqKey="Pokrovsky A" first="A. G." last="Pokrovsky">A. G. Pokrovsky</name><name sortKey="Vlassov, V V" sort="Vlassov, V V" uniqKey="Vlassov V" first="V. V." last="Vlassov">V. V. Vlassov</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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