THERMODYNAMICS OF DRUG-DNA INTERACTIONS
THERMODYNAMICS OF DRUG-DNA INTERACTIONS
复制标题
DOI：
10.1080/07391102.1983.10507457
复制
发表时间：
1983-01-01
影响因子：
4.4
通讯作者：
BRESLAUER, KJ
中科院分区：
文献类型：
--
作者：
MARKY, LA;SNYDER, JG;BRESLAUER, KJ
采用批式量热法、差示扫描量热法（DSC）、紫外可见吸收光谱、荧光光谱和圆二色性（CD）等方法，对道诺霉素、双吡喃、双吡喃和奈托霉素与聚D（AT）和放线菌素D与Salomn睾丸（ST）DNA的结合进行了检测、监测和分析。所有聚d（AT）结合研究均在25 ℃下进行。而放线菌素与ST DNA的结合在1 ℃进行。C提高药物溶解度。这些thermodyamic参数被解释在特定的相互作用，提出了作为模型的一部分，为每种药物的结合。温度依赖性紫外吸收光谱和DSC被用来表征这些药物中的每一种对宿主DNA的热诱导熔融行为的影响。在饱和时，药物结合以如下顺序增加聚d（AT）的热稳定性：奈托霉素>道诺霉素>双吡喃鎓>双吡喃鎓。低于饱和，药物结合到聚d（AT）诱导双相熔融行为，其中2个子转变（结构域）的热分辨率因药物而异。药物的结合常数越高，其增加双链体的热稳定性越多，并且其热分解2个药物诱导的结构域越多。van't霍夫曲线和量热转换曲线的比较表明，每种药物对poly d（AT）的双链体到单链转换的协同性具有不同的影响。通过穿透螺旋的模式结合的药物（例如道诺霉素和双吡喃）显著降低双链体解链的协同性。联茚，其外部结合并诱导交替螺旋结构，实际上增加了双链体解链的协同性。
Batch calorimetry, differential scanning calorimetry (DSC), UV/vis [visible] absorption spectroscopy, fluorescence spectroscopy and circular dichroism (CD), were used to detect, monitor and thermodynamically characterize the binding of daunomycin, dipyrandenium, dipyrandium and netropsin to poly d(AT) and actinomycin D to salomn testes (ST) DNA. All the poly d(AT) binding studies were done at 25.degree. C while actinomycin binding to ST DNA was performed at 1.degree. C to enhance drug solubility. These thermodyamic parameters are interpreted in terms of specific interactions that were proposed as part of models for the binding of each drug. Temperature-dependent UV absorption spectroscopy and DSC were used to characterize the influence of each of these drugs on the thermally-induced melting behavior of the host DNA. At saturation, drug binding increases the thermal stability of poly d(AT) in this order: netropsin > daunomycin > dipyrandium > dipyrandenium. Below saturation, drug binding to poly d(AT) induces biphasic melting behavior in which the thermal resolution of the 2 subtransitions (domains) varies from drug to drug. The higher the binding constant for a drug the more it increases the thermal stability of the duplex and the more it thermally resolves the 2 drug-induced domains. A comparison of the van''t Hoff and the calorimetric transition enthalpies reveals that each drug has a different effect on the cooperativity of the duplex to single strand transition of poly d(AT). Drugs which bind by modes which penetrate the helix (e.g. daunomycin and dipyrandium) significantly reduce the cooperativity of duplex melting. Dipyrandenium, which outside binds and induces an alternating helix structure actually increases the cooperativity of duplex melting.