De Cian Anne, Guittat Lionel, Shin-ya Kazuo, Riou Jean-François, Mergny Jean-Louis
Laboratoire de Biophysique, INSERM U565, CNRS UMR5153, Muséum National d'Histoire Naturelle, 43 rue Cuvier, 75005 Paris, France.
Nucleic Acids Symp Ser (Oxf). 2005(49):235-6. doi: 10.1093/nass/49.1.235.
The telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to directly inhibit telomerase activity. The reactivation of this enzyme in immortalized and most cancer cells suggests that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. In this paper, we have analyzed the stabilization and selectivity of two well-known quadruplex ligands (telomestatin and a cationic porphyrin) towards the human telomeric G-quadruplex species, with FRET. Both molecules strongly stabilize the G-quadruplex, but telomestatin appears much more selective, as shown by competition experiments with double-stranded DNA.
端粒富含G的单链DNA在体外可形成分子内四链体结构，该结构已被证明能直接抑制端粒酶活性。在永生化细胞和大多数癌细胞中这种酶的重新激活表明端粒酶是肿瘤学中的一个相关靶点，并且端粒酶抑制剂已被提议作为新的潜在抗癌药物。在本文中，我们利用荧光共振能量转移分析了两种著名的四链体配体（端粒抑素和一种阳离子卟啉）对人端粒G-四链体物种的稳定性和选择性。两种分子都能强烈稳定G-四链体，但如与双链DNA的竞争实验所示，端粒抑素的选择性似乎要高得多。
