邻菲罗啉化合物：选择性识别基因启动子G-四链体DNAs和双螺旋DNA的光谱学和生理学研究
Spectroscopic and Biological Studies of Phenanthroline Compounds: Selectively Recognize Gene Promoter G-quadruplex DNAs over Duplex DNA
原癌基因启动子区域G-四链体DNA的形成，会阻止转录过程，最终抑制肿瘤的发展，因此，稳定G-四链体DNA的化合物是潜在的抗肿瘤药物。这篇文章通过聚合酶链反应停止(PCR-stop)方法、荧光共振能量转移熔点(FRET-melting)方法、荧光指示剂替代(FID)方法、紫外-可见(UV-vis)吸收光谱、圆二色光谱法研究了三个邻菲罗啉化合物a-c与原癌基因c-kit2和c-myc G-四链体DNAs的相互作用。结果显示：三个化合物都对G-四链体的选择性强于双螺旋，与两种G-四链体的键合常数分别为0.49x106- 3.32x106 M-1（选择性分别为4.1倍到33.2倍）。化合物a, b 和c 对于c-kit2 G-四链体是潜在的稳定剂，熔点升高值12-15℃。CD光谱表明： 这三个化合物对c-kit2 G-四链体结构产生微扰，但是没有明显影响c-myc G-四链体的构象。
G-quadruplex DNA formed in the promoter regions of proto-oncogenes would block the transcription process and eventually suppress the development of tumors, so compounds that stabilize G-quadruplex DNA are potential antitumor drugs. This paper studied interactions of three phenanthroline compounds a-c with proto-oncogene c-kit2 and c-myc G-quadruplex DNAs by means of polymerase chain reaction (PCR) stop assay, fluorescence resonance energy transfer melting (FRET melting) assay, fluorescence indicator displacement (FID) assay, UV-vis absorption, fluorescence and circular dichroism (CD) spectroscopies. Results showed that all three compounds presented selectivity for the G-quadruplex over duplex, with binding constants (Ka) for the both quadruplexes varied from 0.49 x 106 to 3.32 x 106 M-1 (4.1- to 33.2-fold specificity). Compounds a, b and c were potential stabilizers for the c-kit2 G-quadruplex with the melting temperature increase (ΔTm) values of 12-15 oC. CD spectra indicated that the three compounds disrupted the structures of c-kit2 G-quadruplex, whereas no significant change was observed for c-myc G-quadruaplex.
王立华、魏春英
药学肿瘤学生物科学研究方法、生物科学研究技术
生理学c-mycc-kit2G-四链体启动子邻菲罗啉
biologicalc-mycc-kit2G-quadruplexpromoterphenanthroline
王立华,魏春英.邻菲罗啉化合物：选择性识别基因启动子G-四链体DNAs和双螺旋DNA的光谱学和生理学研究[EB/OL].(2012-12-21)[2025-08-24].http://www.paper.edu.cn/releasepaper/content/201212-554.点此复制
评论