Synthesis of phosphorothioate analogues of oligodeoxyribonucleotides and their antiviral activity against human immunodeficiency virus (HIV).
Nuclease-resistant phosphorothioate analogues of oligodeoxynucleotides (oligos) were synthesized by sulfurization of either internucleoside phosphite linkages, in a repetitive manner during chain extension, or internucleoside hydrogen phosphonate linkages, in a single step following chain assembly. These analogues were tested as antiviral agents against human immunodeficiency virus (HIV). In a cytopathic effect inhibition assay using HIV-uninfected susceptible T cells (tetanus toxoid-specific normal T cells) co-cultured with irradiated chronically HIV-infected cells, phosphorothioate oligomers inhibited the cytopathic effect and replication of several isolates of HIV-1 and HIV-2. Thus phosphorothioate analogues of oligos could inhibit cell-to-cell transmission of the virus as well as the infection by cell-free virus particles and also could inhibit a variety of isolates of human retroviruses.
Matsukura
M
M
Clinical Oncology Program, National Cancer Institute, Bethesda, MD 20892.
Zon
G
G
Shinozuka
K
K
Stein
C A
CA
Mitsuya
H
H
Cohen
J S
JS
Broder
S
S
D000998:Antiviral Agents / Q000138:chemical synthesis*; D002460:Cell Line; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D007202:Indicators and Reagents; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013873:Thionucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D007202:Indicators and Reagents; D009838:Oligodeoxyribonucleotides; D013873:Thionucleotides