title: Structure-Activity Relationship Studies of HIV-1 Integrase Oligonucleotide Inhibitors.
abstract: Integration of human immunodeficiency virus type 1 DNA into an infected cell genome is one of the key steps of the viral replication cycle. Therefore, viral enzyme integrase, which realizes the integration, represents an attractive and validated target for the development of new antiviral drugs. In this paper, the anti-integrase activity of a series of conjugates of single-stranded oligonucleotides with hydrophobic molecules was tested, and the structure-activity relationships were also analyzed. Both oligonucleotide and hydrophobic parts of the conjugates influenced the inhibitory potency. Conjugates of 11-mer phosphorothioate oligonucleotides with 6-carboxy-4,7,2',4',5',7'-hexachlorofluorescein (HEX) were found to be the most efficient inhibitors (IC50 = 20 nM) and might be considered as lead compounds for further development of integrase inhibitors.
authors.affiliation: Department of Chemistry, Lomonosov Moscow State University , Leninskie gory 1-3, 119991 Moscow, Russia.
authors.forename: Julia
authors.initials: J
authors.lastname: Agapkina
authors.affiliation: Department of Chemistry, Lomonosov Moscow State University , Leninskie gory 1-3, 119991 Moscow, Russia ; Central Research Institute of Epidemiology , Novogireevskaya street 3a, Moscow 111123, Russia.
authors.forename: Timofei
authors.initials: T
authors.lastname: Zatsepin
authors.affiliation: Belozersky Institute of Physical and Chemical Biology, Lomonosov Moscow State University , Leninskie gory 1, Moscow 119991, Russia.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Knyazhanskaya
authors.affiliation: LBPA, CNRS, Ecole Normale Supérieure de Cachan , 94235 Cachan Cedex, France.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Mouscadet
authors.affiliation: Belozersky Institute of Physical and Chemical Biology, Lomonosov Moscow State University , Leninskie gory 1, Moscow 119991, Russia.
authors.forename: Marina
authors.initials: M
authors.lastname: Gottikh
keywords: HIV-1 integrase; inhibitor; oligonucleotide conjugate; xanthene