de Castro Sonia, García-Aparicio Carlos, Van Laethem Kristel, Gago Federico, Lobatón Esther, De Clercq Erik, Balzarini Jan, Camarasa María-José, Velázquez Sonsoles
Instituto de Química Médica (C.S.I.C.), Juan de la Cierva 3, Madrid, Spain.
Antiviral Res. 2006 Aug;71(1):15-23. doi: 10.1016/j.antiviral.2006.02.009. Epub 2006 Mar 29.
The very first TSAO derivative that lacks the 4''-amino group at the 3'-spiro moiety (compound 3) has been prepared and the effect of this modification on the activity/resistance profile has been evaluated. This molecule proved HIV-1 specific (NNRTI-characteristic). A mixture of wild-type and V106V/A or L234L/I mutations were found in the RT of some, but not all compound 3-resistant virus strains. Compound 3 does not select for the TSAO-specific E138K mutation in the RT. However, the compound markedly lost its antiviral potential against a variety of virus strains that contain NNRTI-characteristic mutations in RT including E138K. The deaminated TSAO compound must fit differently in the HIV-1 RT enzyme than its prototype TSAO-m(3)T.
首个在3'-螺环部分缺少4''-氨基的TSAO衍生物（化合物3）已被制备出来，并评估了这种修饰对活性/耐药性的影响。该分子被证明具有HIV-1特异性（非核苷类逆转录酶抑制剂特性）。在一些但并非所有对化合物3耐药的病毒株的逆转录酶中发现了野生型与V106V/A或L234L/I突变的混合物。化合物3不会在逆转录酶中选择TSAO特异性的E138K突变。然而，该化合物对多种在逆转录酶中含有非核苷类逆转录酶抑制剂特性突变（包括E138K）的病毒株的抗病毒潜力明显丧失。脱氨基的TSAO化合物在HIV-1逆转录酶中的结合方式必定与其原型TSAO-m(3)T不同。
