title: Synthesis of phosphorothioate analogues of oligodeoxyribonucleotides and their antiviral activity against human immunodeficiency virus (HIV).
abstract: 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.
authors.affiliation: Clinical Oncology Program, National Cancer Institute, Bethesda, MD 20892.
authors.forename: M
authors.initials: M
authors.lastname: Matsukura
authors.forename: G
authors.initials: G
authors.lastname: Zon
authors.forename: K
authors.initials: K
authors.lastname: Shinozuka
authors.forename: C A
authors.initials: CA
authors.lastname: Stein
authors.forename: H
authors.initials: H
authors.lastname: Mitsuya
authors.forename: J S
authors.initials: JS
authors.lastname: Cohen
authors.forename: S
authors.initials: S
authors.lastname: Broder
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D007202:Indicators and Reagents; D009838:Oligodeoxyribonucleotides; D013873:Thionucleotides