Guittat Lionel, De Cian Anne, Rosu Frédéric, Gabelica Valérie, De Pauw Edwin, Delfourne Evelyne, Mergny Jean-Louis
Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM UR 565, CNRS UMR 5153, 43 rue Cuvier, 75231 Paris cedex 05, France.
Biochim Biophys Acta. 2005 Aug 5;1724(3):375-84. doi: 10.1016/j.bbagen.2005.04.023.
Ascididemin and Meridine are two marine compounds with pyridoacridine skeletons known to exhibit interesting antitumour activities. These molecules have been reported to behave like DNA intercalators. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of ascididemin and meridine for DNA structures among duplexes, triplexes, quadruplexes and single-strands. Our data confirm that ascididemin and meridine interact with DNA but also recognize triplex and quadruplex structures. These molecules exhibit a significant preference for quadruplexes over duplexes or single-strands. Meridine is a stronger quadruplex ligand and therefore a stronger telomerase inhibitor than ascididemin (IC50=11 and >80 muM, respectively in a standard TRAP assay).
海鞘胺和麦瑞定是两种具有吡啶并吖啶骨架的海洋化合物，已知它们具有有趣的抗肿瘤活性。据报道，这些分子的行为类似于DNA嵌入剂。在本研究中，采用透析竞争试验和质谱实验来确定海鞘胺和麦瑞定对双链体、三链体、四链体和单链等DNA结构的亲和力。我们的数据证实，海鞘胺和麦瑞定与DNA相互作用，同时也能识别三链体和四链体结构。与双链体或单链相比，这些分子对四链体表现出显著的偏好。麦瑞定是一种更强的四链体配体，因此作为端粒酶抑制剂比海鞘胺更强（在标准TRAP试验中，IC50分别为11和>80 μM）。
