STRUCTURAL-FUNCTIONAL ANALYSIS OF BIOPOLYMERS AND THEIR COMPLEXES Inhibition of HIV-1 Integrase 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 integrase is of interest as a target for new antiviral drugs. Conjugates of 11-mer single-stranded oligonucleotides with hydrophobic molecules were shown to be efficient integrase inhibitors, inducing dissociation of the integrase-viral DNA complex. The dependence of the conjugate inhibitory activity on the oligonucleotide length and structure as well as on the structure of hydro- phobic molecules was studied. Conjugates with eosin and oleic acid proved to be the most active. Conjugates of these molecules with 2'-O-methyl-oligonucleotide inhibited integrase at concentrations 50-100 nM but did not influence some other DNA-binding enzymes. DOI: 10.1134/S0026893307010165