An assay for human telomeric G-quadruplex DNA binding drugs

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• 作者：Derrick Watkins ; Nihar Ranjan ; Sunil Kumar ; Changjun Gong ; Dev P. Arya
• 关键词：G-quadruplex ; Telomere ; Aminoglycoside ; TO-neo ; High throughput screen
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：15 December, 2013
• 年：2013
• 卷：23
• 期：24
• 页码：6695-6699
• 全文大小：1118 K

文摘

Compounds that stabilize the G-quadruplexes formed by human telomeres can inhibit the telomerase activity and are potential cancer therapies. We have developed an assay for the screening of compounds with high affinity for human telomeric G-quadruplexes (HTG). The assay uses a thiazole orange fluorescent reporter molecule conjugated to the aminoglycoside, neomycin, as a probe in a fluorescence displacement assay. The conjugation of the planar base stacking thiazole orange with the groove binding neomycin results in high affinity probe that can determine the relative binding affinity of high affinity HTG binding drugs in a high throughput format. The robust assay is applicable for the determination of the binding affinity of HTG in the presence of K⁺ or Na⁺.