The strand transfer oligonucleotide inhibitors of HIV-integrase
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18608742
DOI
10.1080/14756360802051578
PII: 791856647
Knihovny.cz E-resources
- MeSH
- HIV Long Terminal Repeat genetics MeSH
- HIV Integrase drug effects MeSH
- HIV Integrase Inhibitors chemical synthesis pharmacology MeSH
- Nucleic Acid Conformation MeSH
- Phosphorus Acids MeSH
- Molecular Mimicry MeSH
- Oligonucleotides chemical synthesis pharmacology MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- HIV Integrase MeSH
- HIV Integrase Inhibitors MeSH
- Phosphorus Acids MeSH
- Oligonucleotides MeSH
Retroviral integrase participates in two catalytic reactions, which require interactions with the two ends of the viral DNA in the 3'processing reaction, and with a targeted host DNA in the strand transfer reaction. The 3'-hydroxyl group of 2'-deoxyadenosine resulting from the specific removing of GT dinucleotide from the viral DNA in the processing reaction provides the attachment site for the host DNA in a transesterification reaction. We synthesized oligonucleotides (ONs) of various lengths that mimic the processed HIV-1 U5 terminus of the proviral long terminal repeat (LTR) and are ended by 2'-deoxyadenosine containing a 3'-O-phosphonomethyl group. The duplex stability of phosphonomethyl ONs was increased by covalent linkage of the modified strand with its complementary strand by a triethylene glycol loop (TEG). Modified ONs containing up to 10 bases inhibited in vitro the strand transfer reaction catalyzed by HIV-1 integrase at nanomolar concentrations.
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