高等学校化学学报

高等学校化学学报 ›› 2012, Vol. 33 ›› Issue (10): 2217.doi: 10.7503/cjcu20120327

• 分析化学 • 上一篇    下一篇

高选择性端粒G-四链体稳定性配体:9-O-多胺取代小檗碱衍生物的合成及活性评价

马彦1,2, 黄志纾2   

  1. 1. 顺德职业技术学院医学系, 顺德 528333;
    2. 中山大学药学院药物化学研究所, 广州 510080
  • 收稿日期:2012-04-09 出版日期:2012-10-10 发布日期:2012-09-12
  • 通讯作者: 马 彦, 女, 博士, 讲师, 主要从事药物化学、 生物有机化学研究. E-mail: marui-zsu@163.com E-mail:marui-zsu@163.com
  • 基金资助:

    国家自然科学基金(批准号: 20772159, 90813011, U0832005)资助.

Synthesis and Activity Evaluation of 9-O-Substituted Berberine Derivatives Containing Polyamine Chain as Highly Selective Telomeric G-Quadruplex Stabilizing Ligands

MA Yan1,2, HUANG Zhi-Shu2   

  1. 1. Department of Medical Science, Shunde Polytechnic, Shunde 528333, China;
    2. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China
  • Received:2012-04-09 Online:2012-10-10 Published:2012-09-12

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摘要：

设计合成了3个多胺取代的小檗碱衍生物5a~5c, 并利用圆二色(CD)光谱、 荧光共振能量转移(FRET)熔点实验、 荧光光谱和聚合酶链反应(PCR)终止实验等手段研究了小檗碱衍生物5a~5c与端粒DNA的相互作用. 结果表明, 小檗碱衍生物5a~5c可以诱导端粒DNA序列形成反平行结构G-四链体, 显著地提高了端粒G-四链体的稳定性, 有效地抑制了端粒的扩增; 而与双链DNA的相互作用则很小, 是高选择性的端粒G-四链体配体.

关键词: 9-O-多胺取代小檗碱衍生物, 合成, 活性评价, 端粒G-四链体DNA

Abstract:

A series of 9-O-substituted berberine derivatives(5a-5c) as telomeric quadruplex ligands was synthesized and evaluated. The interaction of berberine derivatives with telomeric G-quadruplex DNA was examined by CD spectroscopy, FRET-melting method, fluorescence titration assay and PCR-stop assay. The CD results indicated the derivatives were capable of inducing the formation of antiparallel G-quadruplex and the results from FRET-melting method clearly showed that derivatives with polyamine chain had high binding affinity and superior selectivity for telomeric G-quadruplex DNA over duplex. The PCR-stop assay results exhibited the inhibitory effect on the hybridization. All the results suggested the 9-O-substituted berberine derivatives were highly selective telomeric G-quadruplex DNA stabilizing ligands.

Key words: 9-O-Substituted berberine derivatives containing polyamine chain, Synthesis, Activity evaluation, Telomeric quadruplex DNA

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