[HIV-1 integrase inhibition by modified oligonucleotides: optimization of the inhibitor structure].
Integration of human immunodeficiency virus type 1 DNA into the infected cell genome is one of the key steps of the viral replication cycle. Therefore viral enzyme integrase, which realizes the integration, is of interest as a target for new antiviral drugs. Conjugates of 11-mer single stranded oligonucleotides with hydrophobic molecules are shown to be efficient integrase inhibitors since they induce dissociation of the integrase-viral DNA complex. The effect of the oligonucleotide length and structure as well as the structure of hydrophobic molecules on the conjugate inhibitory activity has been studied. Conjugates with eosin and oleic acid are shown to be the most active. Conjugates of these molecules with 2'-O-methyl-oligonucleotide inhibit integrase at 50-100 nM and have no influence on a number of other DNA-binding enzymes.
Prikazchikova
T A
TA
Volkov
E M
EM
Zubin
E M
EM
Romanova
E A
EA
Gottikh
M B
MB
D004279:DNA, Viral / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D004801:Eosine Yellowish-(YS) / Q000737:chemistry*; D015894:Genome, Human; D019427:HIV Integrase / Q000737:chemistry*; D006801:Humans; D019301:Oleic Acid / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry* / Q000494:pharmacology
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D019301:Oleic Acid; D019427:HIV Integrase; D004801:Eosine Yellowish-(YS)