title: Triplex-mediated inhibition of HIV DNA integration in vitro.
abstract: Integration of human immunodeficiency virus (HIV) DNA into the genome of host cells is an obligatory step in the replicative cycle of the virus. The overall process is carried out in vitro by a single viral protein, the integrase, which binds to short sequences located at the ends of viral DNA long terminal repeats (LTRs). These end sequences are highly conserved in all HIV genomes and are therefore attractive targets for selective DNA binding compounds. The integrase-binding site located in U3 LTR contains a purine motif, 5'-GGAAGGG-3' which can be selectively targeted by oligonucleotide-intercalator conjugates. Under neutral pH and physiological temperature, these conjugates readily form a stable complex with the viral DNA which involves a short DNA triplex. Triple-helix formation prevents the catalytic functions of the integrase in vitro which results in a sequence-specific inhibition of the U3 integration process.
authors.affiliation: Laboratoire de Physicochimie et de Pharmacologie des Macromolécules Biologiques, CNRS URA 147, Institut Gustave-Roussy, PRII, Villejuif, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Mouscadet
authors.forename: S
authors.initials: S
authors.lastname: Carteau
authors.forename: H
authors.initials: H
authors.lastname: Goulaouic
authors.forename: F
authors.initials: F
authors.lastname: Subra
authors.forename: C
authors.initials: C
authors.lastname: Auclair
mesh_terms: D001483:Base Sequence; D002227:Carbazoles / Q000494:pharmacology*; D002474:Cell-Free System; D004247:DNA / Q000378:metabolism; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D019426:Integrases; D007364:Intercalating Agents / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000494:pharmacology*; D016662:Virus Integration / Q000187:drug effects*
chemical_list: D002227:Carbazoles; D004279:DNA, Viral; D007364:Intercalating Agents; D009841:Oligonucleotides; C051802:triplex DNA; C061416:oxazolopyridocarbazole; D004247:DNA; D004254:DNA Nucleotidyltransferases; D019426:Integrases