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 olig...

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Bibliographic Details
Published inMolekuliarnaia biologiia Vol. 41; no. 1; p. 130
Main Authors Prikazchikova, T A, Volkov, E M, Zubin, E M, Romanova, E A, Gottikh, M B
Format Journal Article
LanguageRussian
Published Russia (Federation) 01.01.2007
Subjects
DNA, Viral - chemistry
DNA-Binding Proteins - chemistry
Dose-Response Relationship, Drug
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Eosine Yellowish-(YS) - chemistry
Genome, Human
HIV Integrase - chemistry
Humans
Oleic Acid - chemistry
Oligonucleotides - chemistry
Oligonucleotides - pharmacology
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Summary: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.
ISSN:0026-8984