Sannohe Yuta, Sato Kyosuke, Matsugami Akimasa, Shinohara Ken-ichi, Mashimo Tomoko, Katahira Masato, Sugiyama Hiroshi
Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo, Kyoto, Japan.
Bioorg Med Chem. 2009 Mar 1;17(5):1870-5. doi: 10.1016/j.bmc.2009.01.051. Epub 2009 Jan 29.
Human telomere DNA is of intense interest because of its role in the biology of both cancer and aging. The single-stranded telomere terminus can adopt the structure of a G-quadruplex, which is of particular important for anticancer drug discovery many researchers have reported various G-quadruplex structures in the human telomere. Although the human telomere consists of a number of tandem repeats, higher-order G-quadruplex structures are less discussed due to the complexity of the structures. Here we examined the orientation of the ends of the G-quadruplex structures with consideration given to higher-order structures. We prepared end-extended and (Br)G-substituted oligonucleotides. Native PAGE analysis, CD measurements and NMR spectroscopy showed that the ends of stable G-quadruplex structures point in opposite directions. Our results indicate that the human telomere DNA is likely to form rod-like higher-order structures. This may provide important information for understanding telomere structure and the development of telomere G-quadruplex-binding molecules as telomerase inhibitors.
人类端粒DNA因其在癌症生物学和衰老过程中的作用而备受关注。单链端粒末端可以形成G-四链体结构，这对于抗癌药物的发现尤为重要。许多研究人员已经报道了人类端粒中的各种G-四链体结构。尽管人类端粒由多个串联重复序列组成，但由于结构的复杂性，高阶G-四链体结构较少被讨论。在这里，我们在考虑高阶结构的情况下研究了G-四链体结构末端的方向。我们制备了末端延伸和（Br）G取代的寡核苷酸。天然聚丙烯酰胺凝胶电泳分析、圆二色测量和核磁共振光谱表明，稳定的G-四链体结构的末端指向相反的方向。我们的结果表明，人类端粒DNA可能形成棒状高阶结构。这可能为理解端粒结构以及开发作为端粒酶抑制剂的端粒G-四链体结合分子提供重要信息。
