Dodin G, Schwaller M A, Aubard J, Paoletti C
Groupe de Dynamique des Interactions Macromoleculaires, Institut de Topologie et de Dynamique des Systémes, Paris, France.
Eur J Biochem. 1988 Sep 15;176(2):371-6. doi: 10.1111/j.1432-1033.1988.tb14291.x.
The acid-basic properties of ellipticine have been re-estimated. The apparent pK of protonation at 3 microM drug concentration is 7.4 +/- 0.1. The ellipticine free base (at pH 9, I = 25 mM) intercalates into calf-thymus DNA with an affinity constant of 3.3 +/- 0.2 X 10(5) M-1, and a number of binding sites per phosphate of 0.23. The ellipticinium cation (pH 5, I = 25 mM) binds also to DNA with a constant of 8.3 +/- 0.2 x 10(5) M-1 and at a number of binding sites (n = 0.19). It is postulated that the binding of the drug to DNA at pH 9 is driven by hydrophobic and/or dipolar effects. Even at pH 5, where ellipticine exists as a cation, it is thought that the hydrophobic interaction is the main contribution to binding. The neutral and cationic forms share common binding within DNA sites but yield to structurally different complexes. The free base has 0.04 additional specific binding sites per phosphate. As determined from temperature-jump experiments, the second-order rate constant of the binding of the free base (pH 9) is 3.4 x 10(7) M-1 s-1 and the residence time of the base within the DNA is 8 ms. The rate constant for the binding of the ellipticinium cation is 9.8 x 10(7) M-1 s-1 when it is assumed that drug attachment occurs via a pathway in which the formation of an intermediate ionic complex is not involved (competitive pathway).
椭圆玫瑰树碱的酸碱性质已被重新评估。在药物浓度为3 microM时，质子化的表观pK为7.4±0.1。椭圆玫瑰树碱游离碱（在pH 9，离子强度I = 25 mM时）以3.3±0.2×10⁵ M⁻¹的亲和常数插入小牛胸腺DNA中，每个磷酸的结合位点数为0.23。椭圆玫瑰树碱阳离子（pH 5，I = 25 mM）也以8.3±0.2×10⁵ M⁻¹的常数与DNA结合，结合位点数为0.19。据推测，在pH 9时药物与DNA的结合是由疏水和/或偶极效应驱动的。即使在pH 5时椭圆玫瑰树碱以阳离子形式存在，人们认为疏水相互作用是结合的主要贡献因素。中性和阳离子形式在DNA位点内有共同的结合，但产生结构不同的复合物。游离碱每个磷酸还有0.04个额外的特异性结合位点。根据温度跃变实验确定，游离碱（pH 9）结合的二级速率常数为3.4×10⁷ M⁻¹ s⁻¹，碱在DNA中的停留时间为8毫秒。当假设药物附着通过不涉及中间离子复合物形成的途径（竞争途径）发生时，椭圆玫瑰树碱阳离子的结合速率常数为9.8×10⁷ M⁻¹ s⁻¹。
