Antisense oligonucleotides inhibit in vitro cDNA synthesis by HIV-1 reverse transcriptase. NLM AIDSLINE Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

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Antisense oligonucleotides inhibit in vitro cDNA synthesis by HIV-1 reverse transcriptase.

Antisense Nucleic Acid Drug Dev. 1996 Summer;6(2):103-9. Unique Identifier : AIDSLINE MED/97000182
Boiziau C; Tarrago-Litvak L; Sinha ND; Moreau S; Litvak S; Toulme JJ; INSERM U386, Universite Bordeaux II, France.

Abstract: The inhibition of reverse transcription by various chemically modified antisense oligonucleotides was studied in a cell-free system, composed of an RNA template, a primer oligodeoxynucleotide, and the HIV-1 reverse transcriptase (RT). Different mechanisms of inhibition were observed depending on the chemical structure of the antisense molecule. (1) The hybridization of 2'-O-allyl oligonucleotide to the RNA template promotes a physical arrest of the polymerase. (2) The antisense effect of phosphodiester or phosphorothioate oligonucleotides is essentially due to the RNase H-mediated cleavage of the RNA. (3) A third mechanism was observed with phosphorothioate oligonucleotides that directly interact with the enzyme. Chimeric oligonucleotides, composed of an unmodified region flanked by 2'-O-methyl groups, led to less efficient inhibition than the parent unmodified oligomer, although the inhibitory mechanism was the same. No inhibitory effect was detected when alpha or methylphosphonate oligomers were used.
Keywords: Antiviral Agents/PHARMACOLOGY DNA, Complementary/*BIOSYNTHESIS HIV-1/*DRUG EFFECTS/GENETICS HIV-1 Reverse Transcriptase/DRUG EFFECTS/*GENETICS Oligonucleotides, Antisense/*GENETICS/PHARMACOLOGY Support, Non-U.S. Gov't JOURNAL ARTICLEKWDantiviralagents/pharmacologydna,complementary/KWDbiosynthesishiv-1/KWDdrugeffects/geneticshiv-1reversetranscriptase/drugeffects/KWDgeneticsoligonucleotides,antisense/KWDgenetics/pharmacologysupport,non-uKWDsKWDgov'tjournalarticle
970228
M9721910

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