Institute of Biochemistry, Ernst-Moritz-Arndt University Greifswald , Felix-Hausdorff-Str. 4, D-17487 Greifswald, Germany.
J Phys Chem B. 2017 Jun 15;121(23):5735-5743. doi: 10.1021/acs.jpcb.7b02686. Epub 2017 Jun 2.
Binding of a positively charged indoloquinoline derivative to a G-quadruplex formed by the G-rich promoter element of the c-MYC oncogene was subjected to a rigorous isothermal calorimetric analysis. Binding of the indoloquinoline is primarily enthalpy-driven but is also promoted by a favorable entropy term. Both binding enthalpy ΔH° and binding entropy ΔS° exhibit a noticeable temperature dependence with almost complete enthalpy-entropy compensation as a result of a negative change in heat capacity ΔC°. Salt-dependent polyelectrolyte effects only moderately contribute to the overall free energy of association. More details on the binding process are revealed in an attempt to dissect the total free energy into individual contributory terms. Accordingly, specific intermolecular interactions between the indoloquinoline ligand and G-quadruplex substantially contribute in addition to hydrophobic effects in promoting the association. Comparing thermodynamic profiles for various quadruplex ligands indicates different energetic patterns that may aid in the rational design of more efficient quadruplex binding ligands in the future.
对与 c-MYC 癌基因富含 G 的启动子元件形成的 G-四链体结合的正电荷吲哚喹啉衍生物进行了严格的等温热力学分析。吲哚喹啉的结合主要是由焓驱动的，但也受到有利熵项的促进。结合焓 ΔH°和结合熵 ΔS°都表现出明显的温度依赖性，由于热容 ΔC°的负变化，几乎完全发生焓熵补偿。盐依赖性聚电解质效应仅适度地对总结合自由能做出贡献。在试图将总自由能分解为各个贡献项时，更详细地揭示了结合过程的细节。因此，除了疏水力外，吲哚喹啉配体与 G-四链体之间的特定分子间相互作用也大大促进了结合。比较各种四链体配体的热力学曲线表明，不同的能量模式可能有助于未来合理设计更有效的四链体结合配体。
