Antiviral effect of phosphorothioate oligodeoxyribonucleotides complementary to human immunodeficiency virus
Identifieur interne : 000215 ( Istex/Corpus ); précédent : 000214; suivant : 000216Antiviral effect of phosphorothioate oligodeoxyribonucleotides complementary to human immunodeficiency virus
Auteurs : Sang-Gug Kim ; Toshifumi Hatta ; Satoru Tsukahara ; Hideki Nakashima ; Naoki Yamamoto ; Yoko Shoji ; Kazuyuki Takai ; Hiroshi TakakuSource :
- Bioorganic & Medicinal Chemistry [ 0968-0896 ] ; 1995.
English descriptors
- Teeft :
- Acad, Acceptor, Antisense, Antisense oligomers, Antisense oligonucleotides, Antisense sequences, Antiviral effect, Cellular uptake, Chain length, Chain lengths, Chiba institute, Culture medium, Different target sites, Human immunodeficiency virus, Inhibitory effect, Initiator codon, Mrna processing, Nail acad, Natl, Natl acad, Nucleic acids, Oligomer, Oligomers, Oligonucleotide, Oligonucleotides, Other hand, Particular interest, Phosphorothioate, Phosphorothioate group, Phosphorothioate groups, Phosphorothioate oligodeoxyribonucleotides, Phosphorothioate oligomer, Phosphorothioate oligomers, Phosphorothioate oligonucleotide analogues, Phosphorothioate oligonucleotides, Proc, Random sequence, Replication, Sense sequence, Soodns oligomer, Splice, Splice acceptor, Splice acceptor sites, Target sequences, Target site, Test compounds, Viral, Viral expression, Viral replication.
Abstract
Abstract: Modifications of oligodeoxyribonucleotides include the replacement of the backbone phosphodiester groups with phosphorothioate (S-ODNs) groups and the substitution of phosphorothioate (SO-ODNs) groups at both the 3′- and 5′-ends. In assays for HIV, oligomers (S-ODNs) were more active at the micromolar range than were SO-ODNs of the same sequence. Furthermore, the abilities of antisense-, sense-, random-, and mismatched-oligomers, or homo-oligomers containing internucleotidic phosphorothioate linkages to inhibit HIV-1 replication were examined. Antisense oligonucleotides inhibit the replication and the expression of HIV-1 more efficiently than random-, sense-, mismatched-, and homo-oligomers of the same length or with the same internucleotide modification. Five different target sites (gag, pol, rev, tat, and tar) within the HIV genes were also studied with regard to the inhibition of HIV replication by antisense oligonucleotides. Antisense oligomers complementary to the sites of initiation sequences and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting viral replication was also investigated. Of particular interest was the S-ODNs-rev 15 mer, which possessed higher anti-HIV activity than the sense-, random-, mismatched-, and homo-20 mers.
Url:
DOI: 10.1016/0968-0896(94)00142-P
Links to Exploration step
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<abstract xml:lang="en"><p>Abstract: Modifications of oligodeoxyribonucleotides include the replacement of the backbone phosphodiester groups with phosphorothioate (S-ODNs) groups and the substitution of phosphorothioate (SO-ODNs) groups at both the 3′- and 5′-ends. In assays for HIV, oligomers (S-ODNs) were more active at the micromolar range than were SO-ODNs of the same sequence. Furthermore, the abilities of antisense-, sense-, random-, and mismatched-oligomers, or homo-oligomers containing internucleotidic phosphorothioate linkages to inhibit HIV-1 replication were examined. Antisense oligonucleotides inhibit the replication and the expression of HIV-1 more efficiently than random-, sense-, mismatched-, and homo-oligomers of the same length or with the same internucleotide modification. Five different target sites (gag, pol, rev, tat, and tar) within the HIV genes were also studied with regard to the inhibition of HIV replication by antisense oligonucleotides. Antisense oligomers complementary to the sites of initiation sequences and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting viral replication was also investigated. Of particular interest was the S-ODNs-rev 15 mer, which possessed higher anti-HIV activity than the sense-, random-, mismatched-, and homo-20 mers.</p>
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<head><ce:title>Antiviral effect of phosphorothioate oligodeoxyribonucleotides complementary to human immunodeficiency virus</ce:title>
<ce:author-group><ce:author><ce:given-name>Sang-Gug</ce:given-name>
<ce:surname>Kim</ce:surname>
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<ce:textfn>Department of Industrial Chemistry, Chiba Institute of Technology, Tsudanuma, Narashino, Chiba 275, Japan</ce:textfn>
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<ce:abstract-sec><ce:simple-para>Modifications of oligodeoxyribonucleotides include the replacement of the backbone phosphodiester groups with phosphorothioate (S-ODNs) groups and the substitution of phosphorothioate (SO-ODNs) groups at both the 3′- and 5′-ends. In assays for HIV, oligomers (S-ODNs) were more active at the micromolar range than were SO-ODNs of the same sequence. Furthermore, the abilities of antisense-, sense-, random-, and mismatched-oligomers, or homo-oligomers containing internucleotidic phosphorothioate linkages to inhibit HIV-1 replication were examined. Antisense oligonucleotides inhibit the replication and the expression of HIV-1 more efficiently than random-, sense-, mismatched-, and homo-oligomers of the same length or with the same internucleotide modification. Five different target sites (<ce:italic>gag, pol, rev, tat,</ce:italic>
and <ce:italic>tar</ce:italic>
) within the HIV genes were also studied with regard to the inhibition of HIV replication by antisense oligonucleotides. Antisense oligomers complementary to the sites of initiation sequences and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting viral replication was also investigated. Of particular interest was the S-ODNs-<ce:italic>rev</ce:italic>
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<abstract lang="en">Abstract: Modifications of oligodeoxyribonucleotides include the replacement of the backbone phosphodiester groups with phosphorothioate (S-ODNs) groups and the substitution of phosphorothioate (SO-ODNs) groups at both the 3′- and 5′-ends. In assays for HIV, oligomers (S-ODNs) were more active at the micromolar range than were SO-ODNs of the same sequence. Furthermore, the abilities of antisense-, sense-, random-, and mismatched-oligomers, or homo-oligomers containing internucleotidic phosphorothioate linkages to inhibit HIV-1 replication were examined. Antisense oligonucleotides inhibit the replication and the expression of HIV-1 more efficiently than random-, sense-, mismatched-, and homo-oligomers of the same length or with the same internucleotide modification. Five different target sites (gag, pol, rev, tat, and tar) within the HIV genes were also studied with regard to the inhibition of HIV replication by antisense oligonucleotides. Antisense oligomers complementary to the sites of initiation sequences and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting viral replication was also investigated. Of particular interest was the S-ODNs-rev 15 mer, which possessed higher anti-HIV activity than the sense-, random-, mismatched-, and homo-20 mers.</abstract>
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