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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.

SUBMITTER: Agapkina J

PROVIDER: S-EPMC4018115 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Structure-Activity Relationship Studies of HIV-1 Integrase Oligonucleotide Inhibitors.

Agapkina Julia J Zatsepin Timofei T Knyazhanskaya Ekaterina E Mouscadet Jean-Francois JF Gottikh Marina M

ACS medicinal chemistry letters 20110419 7

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 ...[more]

PMID: 24900345

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