Department of Medicinal Chemistry, College of Pharmacy , University of Sharjah , P.O. Box 27272, Sharjah , United Arab Emirates.
J Med Chem. 2019 Jan 24;62(2):385-402. doi: 10.1021/acs.jmedchem.8b00233. Epub 2018 Aug 14.
Understanding the thermodynamic and binding characteristics of DNA minor groove binders (MGBs) is important for the rational design and development of novel MGBs; however, there are contradicting results in the literature regarding the thermodynamic signature of MGBs. The expansion of the thermodynamic database for MGBs in the literature was encouraging to evaluate and critically test the previously reported hypothesis that MGB binding is mainly entropically driven. In this review, the thermodynamic data of a group of MGBs published in the literature were analyzed to better understand the factors that drive minor groove recognition. Analysis of the enthalpic and entropic contributions to the free energy of binding for 20 interactions from a total of 14 different compounds reveals that MGB binding can be driven by enthalpy, entropy, or by both and that is mainly dictated by ligand structural heterogeneity. These findings could be useful in the design of MGBs for therapeutic purposes.
理解 DNA 小沟结合物（MGBs）的热力学和结合特性对于新型 MGB 的合理设计和开发非常重要；然而，文献中关于 MGB 的热力学特征存在相互矛盾的结果。文献中 MGB 的热力学数据库的扩展令人鼓舞，可以评估和严格测试先前报道的假设，即 MGB 结合主要是由熵驱动的。在这篇综述中，分析了文献中发表的一组 MGB 的热力学数据，以更好地理解驱动小沟识别的因素。对来自总共 14 种不同化合物的 20 个相互作用的结合自由能的焓和熵贡献的分析表明，MGB 结合可以由焓、熵或两者共同驱动，并且主要取决于配体结构的异质性。这些发现可能对治疗目的的 MGB 设计有用。
