小分子药物与DNA分子作用的AFM研究  

AFM study on the interaction between DNA chain and small molecule drugs

作　　者：曹黎黎[1] 朱单[1] 田田[1] 王海涛[1] 黄宁平[1] 肖忠党[1] 

机构地区：[1]东南大学生物电子学国家重点实验室,生物科学与医学工程学院,江苏南京210096

出　　处：《电子显微学报》2011年第2期147-152,共6页Journal of Chinese Electron Microscopy Society

基　　金：国家自然科学基金资助项目(No.61071047)

摘　　要：本文运用原子力显微镜(AFM)研究小分子药物作用于环状双链DNA分子所引起的DNA结构和构象变化。不同浓度药物与DNA分子作用前后的AFM图像显示:长春新碱作用于DNA分子,通过嵌入DNA双螺旋结构的临近碱基对之间,使DNA分子缠绕形成螺旋圈;随药物浓度升高,DNA链被切割成片段,且长度不断减小;至浓度达到一定值,长春新碱化学结构改变,而不与DNA片段发生作用。阿司匹林与DNA分子作用,通过大沟或小沟的碱基对边缘作用叠加在DNA链上,使DNA链的某些部位变构,空间自由度受限而缠绕,随药物浓度升高,缠绕收缩加剧直至形成棒状细丝状,甚至断裂。5-羟色胺作用于DNA分子,DNA链变构缠绕;随药物浓度升高,缠绕程度增强,甚至缠绕成粗棒,其DNA链结构改变与阿司匹林作用下产生的变化基本一致,推测其作用也为插入到大小沟槽中。We used AFM to study the interaction between circular DNA chain and small molecule drugs： vincristine,aspirin and 5-HT.The diverse DNA supercoiled conformations have been successfully imaged under different concentration of drugs.Low vincristine concentration leads to circular DNA chains invariably irregular and folded with no defined superhelix axis.Increasing the vincristine concentration broke DNA chains into small fragments,but high vincristine concentration almost induced no change to the conformation of circular DNA.DNA-aspirin complexes at low aspirin concentration can keep a defined superhelix axis,presenting no obvious change compared with the naked DNA,and the DNA-aspirin binding regions gradually extended with increasing drug concentrations.High concentration of aspirin made DNA chains intertwined into sticks.The performance of complexes of 5-HT-DNA chains is similar to that of aspirin-DNA complexes under concentration of drugs.

关 键 词：原子力显微镜 长春新碱 阿司匹林 5-羟色胺 DNA构象变化 

分 类 号：Q523[生物学—生物化学]