米托蒽醌与生物大分子DNA结合平衡的研究

The Binding Equilibrium of Mitoxantrone and Deoxyribonuleic Acids

米托蒽醌(MX)是一个广谱高效的葸醌类抗癌新药(下式),核酸是该类药物的主要细胞作用靶位,它通过与DNA结合,影响DNA的转译和复制,从而起到抗癌作用。研究这类药物与核酸的作用对于阐明抗癌机理具有重要意义,为此,广泛地开展了这方面的研究。如:MX与DNA存在插入和静电作用、MX浓缩L_(1210)白血病细胞核酸。我们对MX与DNA结合作用过程进行了分析,并计算了MX与DNA结合过程的热力学函数以及结合位点。用McGhee和Von Hippel方程处理配体结合平衡时,可将DNA双螺旋结构看作由N个等同重复单位组成的均匀点阵链分子。假设配体占据其中n个连续点阵单位,当n=1时,即为Scatchard方程所描述的情况,当n>1,同时考虑配体之间的相互作用,得到:

Interaction of mitoxantrone and deoxyribonuleic acids was studied at different phosphate/drug ratios(P/D), and it was found that there are two types of binding processes and interaction models. In a certain range of P/D, one type of model is dominant. At P/D <3, MX leads to condensation of DNA. At higher P/D ratio, MX intercalate into DNA, leading to red-shift of absorption spectra. At P/D>6, MX and DNA are in the binding e-qulibrium, the equilibrium binding constant of MX and calf thymus DNA is 9. 0×105(mol/ L)-1 at 20℃, and the binding site size n is 5. The results indicate that major groove and minor groove may be the most favorable binding sites in the structures of double stranded nucleic acids. There existed anticooperative effects between the binding sites.