Tintori Cristina, Corona Angela, Esposito Francesca, Brai Annalaura, Grandi Nicole, Ceresola Elisa Rita, Clementi Massimo, Canducci Filippo, Tramontano Enzo, Botta Maurizio
Department of Biotechnologies, Chemical and Pharmacy, University of Siena, via Alcide de Gasperi 2, 53100, Siena, Italy.
Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS 554, 09042, Monserrato, Cagliari, Italy.
Chembiochem. 2016 Apr 15;17(8):683-8. doi: 10.1002/cbic.201500668. Epub 2016 Mar 21.
Because HIV-1 reverse transcriptase is an enzyme whose catalytic activity depends on its heterodimeric structure, this system could be a target for inhibitors that perturb the interactions between the protein subunits, p51 and p66. We previously demonstrated that the small molecule MAS0 reduced the association of the two RT subunits and simultaneously inhibited both the polymerase and ribonuclease H activities. In this study, some analogues of MAS0 were rationally selected by docking studies and evaluated in vitro for their ability to disrupt dimeric assembly. Two inhibitors were identified with improved activity compared to MAS0. This study lays the basis for the rational design of more potent inhibitors of RT dimerization.
由于HIV-1逆转录酶是一种催化活性依赖于其二聚体结构的酶，该系统可能成为干扰蛋白质亚基p51和p66之间相互作用的抑制剂的作用靶点。我们之前证明，小分子MAS0可减少两个逆转录酶亚基的结合，同时抑制聚合酶和核糖核酸酶H的活性。在本研究中，通过对接研究合理选择了一些MAS0类似物，并在体外评估它们破坏二聚体组装的能力。与MAS0相比，鉴定出了两种活性有所提高的抑制剂。本研究为合理设计更有效的逆转录酶二聚化抑制剂奠定了基础。
