Cationic porphyrins promote the formation of i-motif DNA and bind peripherally by a nonintercalative mechanism
Cationic porphyrins promote the formation of i-motif DNA and bind peripherally by a nonintercalative mechanism
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DOI：
10.1021/bi001528j
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发表时间：
2000-12-12
期刊：
影响因子：
2.9
通讯作者：
Hurley, LH
中科院分区：
文献类型：
--
作者：
Fedoroff, OY;Rangan, A;Hurley, LH
端粒富含C的链可以形成称为i基序的非规范插入DNA结构。我们研究了阳离子卟啉5，10，15，20-四-（N-甲基-4-吡啶基）卟啉（TMPyP4）与几种含端粒序列的寡核苷酸的i-模体形式的相互作用。发现TMPyP4促进i-motif DNA结构的形成。在H-1 NMR研究的基础上，我们已经创建了一个模型的i-基序-TMPyP4复合物，是与所有可用的实验数据一致。二维NOESY数据提示我们得出结论，TMPyP4通过非嵌入机制特异性结合到嵌入DNA核心的边缘。由于我们已经表明TMPyP4结合并稳定互补的富含G的端粒链的G-四链体形式，这项研究提出了一种有趣的可能性，即TMPyP4可以触发端粒的两条链中不寻常的DNA结构的形成，这反过来又可以解释最近记录的TMPyP4在癌细胞中的生物学效应。
Telomeric C-rich strands can form a noncanonical intercalated DNA structure known as an i-motif. We have studied the interactions of the cationic porphyrin 5,10,15,20-tetra-(N-methyl-4-pyridyl)porphine (TMPyP4) with the i-motif forms of several oligonucleotides containing telomeric sequences. TMPyP4 was found to promote the formation of the i-motif DNA structure. On the basis of H-1 NMR studies, we have created a model of the i-motif-TMPyP4 complex that is consistent with all the available experimental data. Two-dimensional NOESY data prompted us to conclude that TMPyP4 binds specifically to the edge of the intercalated DNA core by a nonintercalative mechanism. Since we have shown that TMPyP4 binds to and stabilizes the G-quadruplex form of the complementary G-rich telomeric strand, this study raises the intriguing possibility that TMPyP4 can trigger the formation of unusual DNA structures in both strands of the telomeres, which may in turn explain the recently documented biological effects of TMPyP4 in cancer cells.