Modukuru Naga K, Snow Kimberly J, Perrin Bradley S, Thota Jyotsna, Kumar Challa V
Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, USA.
J Phys Chem B. 2005 Jun 16;109(23):11810-8. doi: 10.1021/jp050995d.
Systematic studies on the DNA binding of a new anthracene derivative, carrying a 1,8-octyldiamine side chain, were carried out. Calorimetric, spectroscopic, and helix melting studies show that the side chain, consisting of eight methylene groups, enhances the binding constant by a factor of approximately 35 when compared to the binding of a probe lacking the long side chain. Furthermore, the enthalpy of binding of the long-chain derivative to calf thymus DNA (Delta H = 4.1 +/- 0.1 kcal/mol) is far greater than the sum of the enthalpy changes associated with the binding of the probe lacking the long side chain, and the enthalpy for the binding of 1,8-octyldiamine.2HCl. Strong synergistic effects, therefore, are seen with the long-chain derivative. Spectroscopic data indicate bathochromism, strong hypochromism, and quenching of anthryl fluorescence when the above ligand binds to calf thymus DNA. Fluorescence energy transfer studies and circular dichroism data strongly suggest intercalation of the anthryl ring system. The binding stabilizes the double helix, and the helix melting temperature is increased from 78 degrees C to >90 degrees C. The binding to DNA is reversible, depended on the ionic strength, and the major binding mode was suppressed at high ionic strengths and a new mode begins to dominate binding. Substitution of the anthracene ring with 1,8-octyldiamine chain provided a simple method to enhance the binding constant by nearly a factor of 35.
对一种带有1,8 - 辛二胺侧链的新型蒽衍生物的DNA结合进行了系统研究。量热、光谱和螺旋解链研究表明，与缺乏长侧链的探针的结合相比，由八个亚甲基组成的侧链使结合常数提高了约35倍。此外，长链衍生物与小牛胸腺DNA的结合焓（ΔH = 4.1±0.1千卡/摩尔）远大于缺乏长侧链的探针的结合以及1,8 - 辛二胺·2HCl的结合所伴随的焓变之和。因此，长链衍生物表现出强烈的协同效应。光谱数据表明，当上述配体与小牛胸腺DNA结合时，出现红移、强烈的减色效应以及蒽基荧光猝灭。荧光能量转移研究和圆二色性数据强烈表明蒽环系统发生了嵌入。这种结合使双螺旋稳定，螺旋解链温度从78℃升高到>90℃。与DNA的结合是可逆的，取决于离子强度，并且在高离子强度下主要的结合模式受到抑制，一种新的模式开始主导结合。用1,8 - 辛二胺链取代蒽环提供了一种将结合常数提高近35倍的简单方法。
