Schwaller M A, Aubard J, Dodin G
Institut de Topologie et de Dynamique de Systèmes, CNRS URA 34, Université Paris 7, France.
Anticancer Drug Des. 1990 Feb;5(1):77-87.
The temperature-jump (T-jump) method has been used to investigate the binding mechanism to calf-thymus DNA of ellipticine and some of its derivatives. The results show that the plant alkaloid, ellipticine, interacts with DNA at a unique intercalation site whereas most of its synthetic derivatives, such as ellipticinium, 9-hydroxy-ellipticinium and related alkyl-oxazolopyridocarbazoles recognize two distinct DNA sites. Parallel analysis of kinetic data and DNA lengthening abilities of these derivatives suggests that only one of these two DNA sites is an intercalation site. Owing to the determination of the genuine number of drug-DNA complexes (inferred from T-jump experiments) and with the results of thermodynamic investigations (Van't Hoff plots), further characterization of the molecular interactions involved in the binding process was proposed. Thus, the formation of the unique intercalation complex of ellipticine was found to be entropy driven whereas binding of drugs which recognize the second class of binding sites was essentially enthalpy driven. These different thermodynamic behaviors suggest that intercalation essentially results from hydrophobic solvent structure effects in contrast to the second binding mode which principally arises from hydrogen bonding interactions through DNA grooves.
温度跃升（T-jump）方法已被用于研究玫瑰树碱及其一些衍生物与小牛胸腺DNA的结合机制。结果表明，植物生物碱玫瑰树碱在一个独特的嵌入位点与DNA相互作用，而其大多数合成衍生物，如玫瑰树碱盐、9-羟基玫瑰树碱盐及相关的烷基-恶唑并吡啶并咔唑识别两个不同的DNA位点。对这些衍生物的动力学数据和DNA延长能力的平行分析表明，这两个DNA位点中只有一个是嵌入位点。由于确定了药物-DNA复合物的真实数量（从温度跃升实验推断）以及热力学研究的结果（范特霍夫图），有人提出了对结合过程中涉及的分子相互作用进行进一步表征。因此，发现玫瑰树碱独特嵌入复合物的形成是由熵驱动的，而识别第二类结合位点的药物的结合基本上是由焓驱动的。这些不同的热力学行为表明，嵌入主要是由疏水性溶剂结构效应导致的，这与主要通过DNA沟槽中的氢键相互作用产生的第二种结合模式形成对比。
