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Nuclear magnetic resonance studies reveal stabilization of parallel G-quadruplex DNA [d(T2G4T)]4 upon binding to protoberberine alkaloid coralyne
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2016-10-17 14:43:08 Kumar Padmapriya, Ritu Barthwal
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2016-10-17 14:43:08 Kumar Padmapriya, Ritu Barthwal
Stabilization of G-quadruplex DNA structures in human telomeric and proto-oncogenic promoter regions upon ligand binding has evolved as a viable anti-cancer strategy. We have studied interaction of coralyne, a human telomerase inhibiting protoberberine alkaloid, with parallel stranded tetrameric G-quadruplex DNA [d(T2G4T)]4 using Circular Dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. Appearance of induced CD band and the Diffusion Ordered NMR Spectroscopy (DOSY) experiments confirm the formation of well defined coralyne–DNA complex. 1H and 31P NMR studies reveal that coralyne specifically recognizes T2pG3 and G6pT7 steps in DNA. Guanine imino protons indicate that coralyne binding induces thermal stabilization of the G-quadruplex DNA by >20°C. The observed specific changes and thermal stabilization of DNA upon binding may be attributed to inhibition of telomerase by coralyne.
中文翻译:
核磁共振研究表明,与原小ber碱生物碱珊瑚素结合后,平行的G-四链体DNA [d(T2G4T)] 4稳定。
配体结合后,在人类端粒和原癌启动子区域中稳定G-四链体DNA结构已成为一种可行的抗癌策略。我们使用圆二色性(CD)和核磁共振(NMR)光谱研究了珊瑚烯(一种人类端粒酶抑制原小ber碱生物碱)与平行链四聚G-四链体DNA [d(T 2 G 4 T)] 4的相互作用。诱导的CD带的出现和扩散有序NMR光谱学(DOSY)实验证实了形成良好的coralyne-DNA复合物的形成。1 H和31P NMR研究表明,珊瑚烯能特异性识别DNA中的T2pG3和G6pT7步骤。鸟嘌呤亚氨基质子表明,珊瑚素结合在> 20℃下诱导G-四链体DNA的热稳定。观察到结合后DNA的特异性变化和热稳定性可能归因于珊瑚虫对端粒酶的抑制作用。
更新日期:2016-10-18
中文翻译:
核磁共振研究表明,与原小ber碱生物碱珊瑚素结合后,平行的G-四链体DNA [d(T2G4T)] 4稳定。
配体结合后,在人类端粒和原癌启动子区域中稳定G-四链体DNA结构已成为一种可行的抗癌策略。我们使用圆二色性(CD)和核磁共振(NMR)光谱研究了珊瑚烯(一种人类端粒酶抑制原小ber碱生物碱)与平行链四聚G-四链体DNA [d(T 2 G 4 T)] 4的相互作用。诱导的CD带的出现和扩散有序NMR光谱学(DOSY)实验证实了形成良好的coralyne-DNA复合物的形成。1 H和31P NMR研究表明,珊瑚烯能特异性识别DNA中的T2pG3和G6pT7步骤。鸟嘌呤亚氨基质子表明,珊瑚素结合在> 20℃下诱导G-四链体DNA的热稳定。观察到结合后DNA的特异性变化和热稳定性可能归因于珊瑚虫对端粒酶的抑制作用。