The thermodynamics of drug-DNA interactions: ethidium bromide and propidium iodide.
The thermodynamics of drug-DNA interactions: ethidium bromide and propidium iodide.
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药物-DNA 相互作用的热力学：溴化乙锭和碘化丙锭。
DOI：
10.1080/07391102.1987.10506399
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发表时间：
1987
影响因子：
4.4
通讯作者：
Breslauer,KJ
中科院分区：
文献类型：
--
作者：
Chou,WY;Marky,LA;Zaunczkowski,D;Breslauer,KJ
我们首次报道了溴化乙锭(EB)和碘化丙啶(PI)与一系列核酸主体双链体结合的热力学的量热表征。我们的光谱和量热测量结果如下：1.在低盐(16 mM Na+)和25°C下，PI比EB与给定的宿主双链结合得更强。这种PI偏好的大小仅略微依赖于碱基序列，AT碱基对表现出比GC碱基对更大的PI偏好。2.在低盐和25℃下，PI相对于EB的结合增强反映了更有利的PI结合的熵驱动力。3.在较高的盐浓度(216 MM)下，PI结合偏好减弱。4.结合常数(∂lnKb，/∂ln[Na+])与盐的依赖关系表明，PI以正离子形式结合，而EB以单正离子形式结合。5.PI和EB与脱氧均聚体Poly da·Poly DT和Poly da·Poly Du结合时都表现出显著的热熵补偿。我们观察到Netropsin与Poly da·Poly DT均聚物双链结合的类似的焓-熵补偿。因此，我们得出结论，补偿现象是宿主双链体的固有性质，而不是反映结合配体的性质。6.当PI或EB与相应的核糖核型均聚物(Poly Ra·poy RU)结合时，我们没有观察到表征其与脱氧均聚物结合的焓-熵补偿。7.EB和PI与Polyd(AT)·pold(AT)的结合比与Polyd(AU)·pold(AU)的结合更强。具体地说，聚d(AU)·聚d(AU)中没有胸腺嘧啶甲基，使两种药物的结合常数降低了四倍。这种结合的减少是由于不太有利的熵变。在这篇文章中，我们提出并讨论了我们观察到的热力学和超热力学数据的可能的分子起源。特别是，当我们提出与我们的热力学数据一致的分子解释时，我们唤起了涉及药物和宿主双链的溶剂效应。
We report the first calorimetrically-derived characterization of the thermodynamics of ethidium bromide (EB) and propidium iodide (PI) binding to a series of nucleic acid host duplexes. Our spectroscopic and calorimetric measurements yield the following results:1.At low salt (16mM Na+) and 25°C, PI binds more strongly than EB to a given host duplex. The magnitude of this PI preference depends only marginally on base sequence, with AT base pairs showing a greater PI preference than GC base pairs.2.The enhanced binding of PI relative to EB at low salt and 25°C reflects a more favorable entropie driving force for PI binding.3.The PI binding preference diminishes at higher salt concentrations (216mM). In other words, the binding preference is electrostatic in origin.4.The salt dependence of the binding constants (∂lnKb,/∂ln[Na+]) reveal that PI binds as a dication while EB binds as a monocation.5.PI and EB both exhibit impressive enthalpy-entropy compensations when they bind to the deoxy homopolymers poly dA · poly dT and poly dA · poly dU. We have observed a similar enthalpy-entropy compensation for netropsin binding to the poly dA · poly dT homopolymer duplex. We therefore conclude that the compensation phenomenon is an intrinsic property of the host duplex rather than reflecting a property of the binding ligand.6.When either PI or EB bind to the corresponding ribo homopolymer (poly rA · poy rU) we do not observe the enthalpy-entropy compensation that characterizes the binding to the deoxy homopolymer.7.EB and PI both bind more strongly to poly d(AT) · poly d(AT) than to poly d(AU) · poly d(AU). Specifically, the absence of the thymine methyl group in poly d(AU) · poly d(AU) reduces the binding constant of both drugs by a factor of four. This reduction in binding is due to a less favorable entropy change.In this paper we present and discuss possible molecular origins for our observed thermodynamic and extra-thermodynamic data. In particular, we evoke solvent effects involving both the drugs and the host duplexes when we propose molecular interpretations which are consistent with our thermodynamic data.