阳离子金属卟啉与四螺旋DNA相互作用的研究

Study on the interaction between cationic metallo-porphyrins and G-quadruplex DNA

目的探讨金属阳离子卟啉的合成方法及与四螺旋DNA的相互作用方式。方法采用紫外可见吸收光谱、圆二色谱和荧光光谱等方法对一系列阳离子卟啉与四螺旋DNA的结合模式、结合常数及稳定四螺旋DNA情况进行研究。结果自由阳离子卟啉及金属铜卟啉可以插入到四螺旋DNA的碱基序列中,与四螺旋DNA的结合常数分别达到8.2×104和7.4×104,锌卟啉和锰卟啉分别采用堆积和沟面结合方式与四螺旋DNA相结合,结合常数分别为3.3×104和2.9×104。结论金属阳离子卟啉与四螺旋DNA的作用情况受到配位金属离子的影响;四配位的金属卟啉具有更高的DNA亲和力,有望作为潜在的抗肿瘤药物。

Objective To study the synthesis methods of a serious of cationic metallo-porphyrins and their interaction with G-quadruplex DNA.Methods The binding modes and intrinsic binding constants（Kb） of cationic metallo-porphyrins with G-quadruplex DNA were studied comparatively by the combination of absorption spectroscopy,circular dichroism（CD） spectroscopy and fluorescence spectroscopy.Results It was found that the free porphyrin and Cu（II） porphyrin could insert into the bases of G-quadruplex DNA,with Kb values of 8.2 × 10^4and 7.4 × 10^4,respectively.However,Zn（II） and Mn（III） porphyrins employed outside binding and groove binding modes to bind with G4 DNA,with Kbvalues of 3.3×104and 2.9×10^4,respectively.Conclusion The interaction of these porphyrins with G-quadruplex DNA was significantly influenced by different metals coordinated with the porphyrin plane.Metallo-porphyrins with four-coordination structure had higher binding affinities and thus was better anti-cancer candidates than other metallo-porphyrins.