Binding of indoloquinolines with different aliphatic side chains to a parallel G-quadruplex derived from the MYC promoter sequence was characterized by optical and calorimetric measurements. ITC experiments performed at different temperatures enabled the determination of molar heat capacity changes upon quadruplex binding and a partitioning of the total binding free enthalpy into contributing terms with hydrophobic effects being major driving forces for all derivatives. Whereas affinities increase for indoloquinolines equipped with a long and positively charged side arm, the highest contribution of specific intermolecular interactions anticipated to impart enhanced specificity is found for a ligand with an uncharged ether aliphatic tail. Obtained thermodynamic signatures may considerably aid in the rational selection of ligand side chains for G-quadruplex binders with enhanced affinity or selectivity.

吲哚喹啉与不同脂肪族侧链的结合与MYC衍生的平行G-四链体的结合通过光学和量热测量来表征启动子序列。在不同温度下进行的ITC实验能够确定四链体结合时摩尔热容变化，以及将总结合自由焓划分为贡献项，而疏水作用是所有衍生物的主要驱动力。配备长且带正电荷的侧臂的吲哚喹啉的亲和力增加，而对于具有不带电荷的醚脂族尾部的配体，发现预期会赋予增强的特异性的特定分子间相互作用的最大贡献。获得的热力学特征可以极大地帮助以增强的亲和力或选择性为G-四链体粘合剂合理地选择配体侧链。