Rau D C
Division of Computer Research and Technology, National Institutes of Health, Bethesda, MD 20892.
Biopolymers. 1995 Apr;35(4):377-84. doi: 10.1002/bip.360350405.
The binding of a netropsin analogue to random sequence DNA, monitored by CD, is seen dependent on the concentration of neutral solutes. The binding free energy decreases linearly with solute osmolal concentration and the magnitude of the effect is insensitive to the chemical identity of the solute for betaine, sorbitol, and triethylene glycol. These solutes appear to modulate binding through their effect on water activity and changes in the hydration of the drug and DNA in the complex reaction, not through a direct interaction with the reactants or the product. The dependence of binding constant on solute concentration can be interpreted as an additional binding of some 50-60 extra solute excluding water molecules by the complex. A water sensitivity of drug binding is further seen from the dependence of binding constants on the type of anion in solution. Anions in the Hofmeister series strongly affect bulk water free energies and entropies. The differences in netropsin analogue binding to DNA with Cl-, F-, and ClO4- are consistent with the effect observed with neutral solutes. The ability to measure changes in water binding associated with a specific DNA interaction is a first step toward correlating changes in hydration with the strength and specificity of binding.
通过圆二色光谱监测，发现一种纺锤菌素类似物与随机序列DNA的结合取决于中性溶质的浓度。结合自由能随溶质重量摩尔浓度呈线性下降，对于甜菜碱、山梨醇和三甘醇，这种效应的大小对溶质的化学性质不敏感。这些溶质似乎是通过影响水活度以及复合物反应中药物和DNA水合作用的变化来调节结合，而不是通过与反应物或产物的直接相互作用。结合常数对溶质浓度的依赖性可以解释为复合物额外结合了约50 - 60个除水分子之外的溶质。从结合常数对溶液中阴离子类型的依赖性还可以进一步看出药物结合对水的敏感性。霍夫迈斯特序列中的阴离子强烈影响大量水的自由能和熵。纺锤菌素类似物与含有Cl-、F-和ClO4-的DNA结合的差异与中性溶质所观察到的效应一致。测量与特定DNA相互作用相关的水结合变化的能力是将水合作用变化与结合强度和特异性相关联的第一步。
