Agapkina Julia, Zatsepin Timofei, Knyazhanskaya Ekaterina, Mouscadet Jean-Francois, Gottikh Marina
Department of Chemistry, Lomonosov Moscow State University , Leninskie gory 1-3, 119991 Moscow, Russia.
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.
ACS Med Chem Lett. 2011 Apr 19;2(7):532-7. doi: 10.1021/ml200066k. eCollection 2011 Jul 14.
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.
1型人类免疫缺陷病毒DNA整合到受感染细胞基因组中是病毒复制周期的关键步骤之一。因此，实现整合的病毒酶整合酶是开发新型抗病毒药物的一个有吸引力且经过验证的靶点。本文测试了一系列单链寡核苷酸与疏水分子缀合物的抗整合酶活性，并分析了构效关系。缀合物的寡核苷酸部分和疏水部分均影响抑制效力。发现11聚体硫代磷酸酯寡核苷酸与6-羧基-4,7,2',4',5',7'-六氯荧光素（HEX）的缀合物是最有效的抑制剂（IC50 = 20 nM），可被视为整合酶抑制剂进一步开发的先导化合物。
