Document 0628
 DOCN  M9490628
 TI    Triplex-mediated inhibition of HIV DNA integration in vitro.
 DT    9411
 AU    Mouscadet JF; Carteau S; Goulaouic H; Subra F; Auclair C; Laboratoire de
       Physicochimie et de Pharmacologie des; Macromolecules Biologiques, CNRS
       URA 147, Institut; Gustave-Roussy, PRII, Villejuif, France.
 SO    J Biol Chem. 1994 Aug 26;269(34):21635-8. Unique Identifier : AIDSLINE
       MED/94342354
 AB    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.
 DE    Base Sequence  Carbazoles/*PHARMACOLOGY  Cell-Free System  Comparative
       Study  DNA/METABOLISM  DNA Nucleotidyltransferases/METABOLISM  DNA,
       Viral/METABOLISM  HIV Long Terminal Repeat/DRUG EFFECTS  HIV-1/*DRUG
       EFFECTS/GROWTH & DEVELOPMENT/GENETICS  Intercalating
       Agents/*PHARMACOLOGY  Molecular Sequence Data
       Oligonucleotides/*PHARMACOLOGY  Support, Non-U.S. Gov't  Virus
       Integration/*DRUG EFFECTS  JOURNAL ARTICLE

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