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M9490628.TXT
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1994-09-24
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).