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Application of circular dichroism to the study of interactions between small molecular compounds and DNA

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Author:: No author available

Journal Title:: ACTA PHARMACEUTICA SINICA

Issue:: 12

DOI:: No doi available

Key Word:: 圆二色谱;诱导圆二色谱;抗肿瘤药;药物与DNA相互作用;DNA嵌入;DNA沟结合

Abstract：圆二色谱(CD)是研究DNA构象随环境条件(如温度、离子强度和pH)的改变而变化的检测技术,也是研究DNA与配基(包括小分子和蛋白质等大分子)相互作用的有力工具.DNA的圆二色谱是由其骨架结构中的不对称糖分子和由这些糖分子的构型决定的螺旋结构产生的.根据配基对原有的DNA圆二色谱信号的影响,以及诱导产生的圆二色谱新信号(ICD)的不同特点,不仅可以得知配基与DNA具有相互作用,还可以推断配基与DNA结合的不同模式.研究表明这些ICD信号是由配基的电子跃迁偶极矩与DNA的碱基电子跃迁偶极矩在DNA不对称环境中发生偶合产生的.如果使用不同序列的短链DNA进行深入的研究,还可获知配基与DNA相互作用中的序列特异性.实验已经证明,圆二色谱法虽然灵敏度较低,但它具有快速、简便、样品用量少、对构象变化敏感及不受分子大小的限制等特点,可以作为核磁共振(NMR)和X-光单晶衍射技术的补充.本文将介绍圆二色谱技术在研究DNA与小分子化合物相互作用中的应用以及本实验室利用圆二色谱技术研究抗肿瘤新药的初步结果.由于圆二色谱可作为新药研究中发现先导化合物辅助筛选的手段,因此可用于发现更多以DNA为靶点的药物,如抗肿瘤药、抗菌药、抗病毒药等.

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