CAJ | 학술논문

在人体生理条件下(pH 7.4),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相瓦作用的荧光光谱,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,作用力类型足以氢键和静电作用为主,此过程是放热的焓熵协旧驱动过程.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.
재인체생리조건하(pH 7.4),이용자외광보법화형광광보법연구료본실험실합성적유홍매소연생물DNR-D3여소우흉선DNA(ctDNA)적상호작용.실험발현,재ctDNA존재하DNR-D3적자외흡수광보발생감색효응차출현홍이현상,저표명DNR-D3여ctDNA상호작용적결합방식이감삽위주.통과20,30,37℃조건하ctDNA여DNR-D3상와작용적형광광보,판단ctDNA여DNR-D3지간형광졸멸방식위정태졸멸.이용형광수거계산불동온도하적결합상수,결합위점수급열역학삼수,종이판단DNR-D3여ctDNA적작용방식이감삽위주,작용력류형족이경건화정전작용위주,차과정시방열적함적협구구동과정.DNR-D3적형광졸멸50%시DNR-D3여ctDNA적마이농도비Rc=7/25,저표명DNR-D3적은배여ctDNA발생료강렬적감삽작용,DNR-D3현시출료교강적항암활성.통과연구가지,DNR-D3유망성위항암활성후선약물.
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.