The orientation of the ends of G-quadruplex structures investigated using end-extended oligonucleotides

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• 作者：Yuta Sannohe ; Kyosuke Sato ; Akimasa Matsugami ; Ken-ichi Shinohara ; Tomoko Mashimo ; Masato Katahira ; Hiroshi Sugiyama
• 关键词：G-quadruplex ; Telomere ; CD ; Gel electrophoresis ; Cancer
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2009
• 出版时间：1 March 2009
• 年：2009
• 卷：17
• 期：5
• 页码：1870-1875
• 全文大小：537 K

文摘

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 ^BrG-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.