Rabbani Azra, Abdosamadi Sayeh, Sari-Saraf Naghmeh
Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, 13145-1384, Tehran, Iran.
Acta Pharmacol Sin. 2007 May;28(5):731-7. doi: 10.1111/j.1745-7254.2007.00542.x.
The interaction of anthracycline anticancer drugs with chromatin, nucleosomes and histone H1 has been extensively studied. In the present study, for the first time, we have investigated the binding of anthracycline antibiotic, daunomycin, to free and cross-linked thymus core histones (CL-core) in solution and in the absence of DNA.
Fluorescence, UV/Vis spectroscopy and equilibrium dialysis techniques were used.
The UV spectroscopy results show that daunomycin induces hypochromicity in the absorption spectra of the core histones. Fluorescence emission intensity is decreased upon daunomycin binding and the process is concentration dependent. The equilibrium dialysis shows that the binding is positive cooperative with the binding sites as Scatchard plot and Hill Coefficient confirm it.
The results suggest that daunomycin shows much higher affinity to core histones free in solution than to CL-core, implying that the binding is most likely due to the accessibility of these proteins to the environment. It is suggested that daunomycin binds strongly to open state of histones, such as in tumor cells, rather than to their compact structure seen in normal chromatin.
蒽环类抗癌药物与染色质、核小体和组蛋白H1的相互作用已得到广泛研究。在本研究中，我们首次在无DNA的溶液中研究了蒽环类抗生素柔红霉素与游离及交联胸腺核心组蛋白（CL-核心）的结合情况。
采用荧光、紫外/可见光谱和平衡透析技术。
紫外光谱结果表明，柔红霉素可使核心组蛋白的吸收光谱发生减色效应。柔红霉素结合后荧光发射强度降低，且该过程呈浓度依赖性。平衡透析表明，结合具有正协同性，Scatchard图和希尔系数证实了这一点。
结果表明，柔红霉素对溶液中游离的核心组蛋白的亲和力远高于对CL-核心的亲和力，这意味着这种结合很可能是由于这些蛋白质对环境的可及性。提示柔红霉素与组蛋白的开放状态（如肿瘤细胞中的状态）结合紧密，而不是与正常染色质中所见的紧密结构结合。
