Riou Jean-François, Gomez Dennis, Lemarteleur Thibault, Trentesaux Chantal
Institut fédératif de recherche 53, UFR de Pharmacie, Université de Reims-Champagne-Ardenne, 51, rue Cognacq-Jay, 51096 Reims.
Bull Cancer. 2003 Apr;90(4):305-13.
The peculiar sequence of telomeric DNA, composed of repetitions of the GGTTAG motif allows the formation of an unusual DNA conformation based on guanine-quadruplex (G-quadruplex). Small molecules that bind and stabilize telomeric DNA under its G-quadruplex conformation are able to impair telomerase activity. Several recent reports have shown that G-quadruplex ligands could block telomerase activity in cancer cells and represent a new experimental approach to limit cancer growth. The intracellular existence of G-quadruplex structure is still controversial, since no direct proof allowed to establish its reality. Many sequences of nucleic acids in the mammalian genome are able to form a G-quadruplex in vitro and several proteins have been described to interact in vitro with G-quadruplex. These data indicated that G-quadruplex are members of a family of target structures larger than that initially described at telomeres, and raised the question of the selectivity and therapeutic index of their ligands in the context of an antitumor therapy.
端粒DNA的特殊序列由GGTTAG基序的重复组成,能够形成基于鸟嘌呤四链体(G-四链体)的异常DNA构象。在其G-四链体构象下结合并稳定端粒DNA的小分子能够损害端粒酶活性。最近的几份报告表明,G-四链体配体可以阻断癌细胞中的端粒酶活性,并代表了一种限制癌症生长的新实验方法。G-四链体结构在细胞内的存在仍然存在争议,因为没有直接证据能够证实其真实性。哺乳动物基因组中的许多核酸序列在体外能够形成G-四链体,并且已经描述了几种蛋白质在体外与G-四链体相互作用。这些数据表明,G-四链体是一个靶结构家族的成员,该家族比最初在端粒处描述的要大,并提出了其配体在抗肿瘤治疗背景下的选择性和治疗指数问题。