Thermodynamic characterization of the multivalent binding of chartreusin to DNA
Thermodynamic characterization of the multivalent binding of chartreusin to DNA
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DOI：
10.1093/nar/gkf558
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发表时间：
2002-10-15
影响因子：
14.9
通讯作者：
Portugal, J
中科院分区：
文献类型：
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作者：
Barceló, F;Capó, D;Portugal, J
DNA-药物相互作用的热力学特性是药物合理设计的重要组成部分.等温滴定量热法（ITC）、差示扫描量热法（DSC）和UV熔融实验已被用于分析抗肿瘤抗生素夏曲菌素与DNA的多价（嵌入加小沟）结合。在配体存在的情况下，使用DNA UV熔解研究和ITC测定的结合焓，我们确定在20 ℃下，在含有18 mM Na+的溶液中，相互作用的结合常数为3.6 x 10（5）M-1。DNA-药物相互作用是焓驱动的，在20 ℃时Δ H（B）为-7.07 kcal/mol。通过ITC在20- 35 ℃范围内测定结合率，并用于计算结合诱导的热容变化（Δ Cp）为-391 cal/mol K。我们已经获得了详细的热力学配置文件，这种多价药物的相互作用，这使得可能的解剖DeltaG（obs）到组件的自由能项。从溶液到DNA嵌入位点的Chartreusin发色团的疏水转移是结合自由能的主要贡献者。
Characterization of the thermodynamics of DNA- drug interactions is a very useful part in rational drug design. Isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC) and UV melting experiments have been used to analyze the multivalent (intercalation plus minor groove) binding of the antitumor antibiotic chartreusin to DNA. Using DNA UV melting studies in the presence of the ligand and the binding enthalpy determined by ITC, we determined that the binding constant for the interaction was 3.6 x 10(5) M-1 at 20degreesC, in a solution containing 18 mM Na+. The DNA-drug interaction was enthalpy driven, with a DeltaH(b) of -7.07 kcal/mol at 20degreesC. Binding enthalpies were determined by ITC in the 20-35degreesC range and used to calculate a binding-induced change in heat capacity (DeltaCp) of -391 cal/mol K. We have obtained a detailed thermodynamic profile for the interaction of this multivalent drug, which makes possible a dissection of DeltaG(obs) into the component free energy terms. The hydrophobic transfer of the chartreusin chromophore from the solution to the DNA intercalating site is the main contributor to the free energy of binding.