Schwaller M A, Dodin G, Aubard J
Institut de Topologie et Dynamique des Systèmes de l'Université Paris VII, CNRS UA 34, France.
Biopolymers. 1991 Apr;31(5):519-27. doi: 10.1002/bip.360310507.
Viscosimetric and kinetic results allow one to characterize three modes of DNA binding in the ellipticine series: (1) Ellipticine and its 9 methoxy derivative, which present maximal DNA lengthening properties and bind DNA through a single step mechanism, can be considered as pure intercalators. (2) Ellipticinium derivatives and short-chain substituted oxazolopyridocarbazoles, which present intermediate DNA lengthening properties, bind DNA through a two-step mechanism, one being intercalation. (3) Long-chain substituted oxazolopyridocarbazole derivatives, which display the smallest DNA lengthening properties, bind DNA through a single-step mechanism, probably resulting from an outside binding mode. The viscosimetric and kinetic results are compared with the thermodynamic results obtained from the temperature dependence of the binding constants. It appears that drugs binding on the outside of the DNA double helix tend to have large enthalpy and small entropy contributions, whereas pure intercalating drugs have contributions from both enthalpy and entropy, with entropy dominating by about 2:1. Drugs showing two binding modes exhibit a continuum between the aforementioned extremes, with no breaks in behavior. From this comparison, a correlation between thermodynamic data and DNA binding modes is proposed. Possible molecular implications of both enthalpy and entropy to DNA binding free energy are discussed.
粘度测定和动力学结果使人们能够表征椭圆玫瑰树碱系列中三种DNA结合模式：（1）椭圆玫瑰树碱及其9-甲氧基衍生物具有最大的DNA延长特性，并通过单步机制结合DNA，可被视为纯嵌入剂。（2） 玫瑰树碱衍生物和短链取代的恶唑并吡啶并咔唑具有中等的DNA延长特性，通过两步机制结合DNA，其中一步是嵌入。（3） 长链取代的恶唑并吡啶并咔唑衍生物具有最小的DNA延长特性，通过单步机制结合DNA，这可能是由外部结合模式导致的。将粘度测定和动力学结果与从结合常数的温度依赖性获得的热力学结果进行了比较。结果表明，结合在DNA双螺旋外部的药物往往具有较大的焓贡献和较小的熵贡献，而纯嵌入药物的焓和熵都有贡献，熵以约2:1的比例占主导。表现出两种结合模式的药物在上述极端情况之间呈现出连续性，行为上没有间断。通过这种比较，提出了热力学数据与DNA结合模式之间的相关性。讨论了焓和熵对DNA结合自由能的可能分子影响。
