光谱法研究柔红霉素衍生物DNR-D3与DNA相互作用

在人体生理条件下(pH7.4),利用紫外光谱法和荧光光谱法研究了本实验室合成的柔红霉素衍生物DNR-D3与小牛胸腺DNA(ctDNA)的相互作用。实验发现,在ctDNA存在下DNR-D3的紫外吸收光谱发生减色效应且出现红移现象,这表明DNR-D3与ctDNA相互作用的结合方式以嵌插为主。通过20,30,37℃条件下ctDNA与DNR-D3相互作用的荧光光谱,判断ctDNA与DNR-D3之间荧光猝灭方式为静态猝灭。利用荧光数据计算不同温度下的结合常数,结合位点数及热力学参数,从而判断DNR-D3与ctDNA的作用方式以嵌插为主,作用力类型是以氢键和静电作用为主,此过程是放热的焓熵协同驱动过程。DNR-D3的荧光猝灭50%时DNR-D3与ctDNA的摩尔浓度比Rc=7/25,这表明DNR-D3的蒽环与ctDNA发生了强烈的嵌插作用,DNR-D3显示出了较强的抗癌活性。通过研究可知,DNR-D3有望成为抗癌活性候选药物。

Study on the Interaction between DNR-D3 (Daunorubicin Derivative) and ctDNA by Spectroscopic Methods

The interaction of DNR-D3(daunorubicin derivative) synthesized in our laboratory with ctDNA was investigated by UV spectrum and fluorescence spectrum under physiological conditions (pH 7.4) for the first time.The red shifts and hypochromicities were observed from the absorption titration experiments.These results suggest that DNR-D3 was intercalated into the DNA base pairs.Through the fluorescence quenching data measured at different temperatures (20 ℃,30 ℃ and 37 ℃),it is known that the quenching mechanism of fluorescence of DNR-D3 by ctDNA is a static quenching type.On the other band,the binding constant,the number of binding sites and thermodynamic parameters were also obtained.These data also indicate that the binding mode of the interaction between DNR-D3 and ctDNA is intercalation.Additionally,the types of interaction force are mainly hydrogen bonding and electrostatic interaction,and the binding is exothermic enthalpy-entropy cooperative driven process.When the degree of fluorescence quenching of DNR-D3 is 50%,the ratio of the molar concentration of DNR-D3 to ctDNA is 7/25,which indicates that the DNR-D3 anthracycline was intercalated into the DNA base pairs and that DNR-D3 showed a strong anticancer activity.DNR-D3 is expected to become one of the drug candidates from our investigations.