Document 0706
 DOCN  M9590706
 TI    Triplex-mediated inhibition of hiv dna integration in vitro
 DT    9509
 AU    Auclair C; Mouscadet J; Carteau S; Goulaouic H; Subra F; Laboratoire de
       Physicochimie et de Pharmacologie des; Macromolecules Biologiques,
       Institut Gustave-Roussy, Villejuif,; France.
 SO    NIH Conf Retroviral Integrase. 1995 Jan 19-20;:(Session III, speakers'
       abstracts - unpaged). Unique Identifier : AIDSLINE AIDS/95920013
 AB    Integration of 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 (IN),
       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'GGAAGGG3' which can be selectively targeted by
       oligonucleotideintercalator conjugates
       (oligopurines-oxazolopyridocarbazole). Under neutral pH and at
       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, including both endonucleolytic cleavage and strand transfer,
       which results in a sequence-specific inhibition of the U3 integration
       process. This approach can be extended to the targeting of U5 end
       sequence 5'-GGAAAA/3'-AGAGA using oligonucleotides which form
       alternate-strand triple-helix.
 DE    Base Sequence  Binding Sites  DNA  DNA
       Nucleotidyltransferases/METABOLISM  DNA, Viral/*GENETICS  Genome, Viral
       HIV Long Terminal Repeat  HIV-1/ENZYMOLOGY/*GENETICS  Hydrogen-Ion
       Concentration  Hydrolysis  Molecular Sequence Data  Purines/METABOLISM
       Temperature  Virus Integration/*GENETICS  MEETING ABSTRACT

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