Han Feixue, Chalikian Tigran V
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Ontario M5S 2S2, Canada.
J Am Chem Soc. 2003 Jun 18;125(24):7219-29. doi: 10.1021/ja030068p.
We use high precision ultrasonic velocimetric and densimetric techniques to determine at 25 degrees C the changes in volume, deltaV, and adiabatic compressibility, deltaK(S), that accompany the binding of ethidium to the poly(rA)poly(rU), poly(dAdT)poly(dAdT), poly(dGdC)poly(dGdC), and poly(dIdC)poly(dIdC) duplexes, as well as to the poly(rU)poly(rA)poly(rU) triplex. The binding of ethidium to each of the duplexes and the triplex is accompanied by negative changes in volume, deltaV, and adiabatic compressibility, deltaK(S). We discuss the basis for relating macroscopic and microscopic properties, particularly, emphasizing how measured changes in volume and compressibility can be quantitatively interpreted in terms of the differential hydration properties of DNA and RNA structures in their ligand-free and ligand-bound states. We also estimate the entropic cost of intercalation-induced changes in hydration of each of the nucleic acid structures and the drug. In general, our results emphasize the vital role of hydration in modulating the energetics of drug-DNA binding, while also underscoring the fact that hydration must be carefully taken into account in analysis and prediction of the energetics of nucleic acid recognition.
我们使用高精度超声测速和测密技术，在25摄氏度下测定溴化乙锭与聚（rA）聚（rU）、聚（dAdT）聚（dAdT）、聚（dGdC）聚（dGdC）和聚（dIdC）聚（dIdC）双链体以及聚（rU）聚（rA）聚（rU）三链体结合时伴随的体积变化ΔV和绝热压缩率变化ΔK(S)。溴化乙锭与每种双链体和三链体的结合都伴随着体积变化ΔV和绝热压缩率变化ΔK(S)的负值。我们讨论了将宏观和微观性质联系起来的基础，特别强调了如何根据DNA和RNA结构在无配体和有配体状态下的差异水合性质，对测得的体积和压缩率变化进行定量解释。我们还估计了嵌入诱导的每种核酸结构和药物水合变化的熵成本。总体而言，我们的结果强调了水合作用在调节药物 - DNA结合能量方面的重要作用，同时也强调了在分析和预测核酸识别能量时必须仔细考虑水合作用这一事实。
