Erlitzki Noa, Huang Kenneth, Xhani Suela, Farahat Abdelbasset A, Kumar Arvind, Boykin David W, Poon Gregory M K
Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States.
Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Biophys Chem. 2017 Dec;231:95-104. doi: 10.1016/j.bpc.2017.02.008. Epub 2017 Mar 20.
Previous investigations of sequence-specific DNA binding by model minor groove-binding compounds showed that the ligand/DNA complex was destabilized in the presence of compatible co-solutes. Inhibition was interpreted in terms of osmotic stress theory as the uptake of significant numbers of excess water molecules from bulk solvent upon complex formation. Here, we interrogated the AT-specific DNA complex formed with the symmetric heterocyclic diamidine DB1976 as a model for minor groove DNA recognition using both ionic (NaCl) and non-ionic cosolutes (ethylene glycol, glycine betaine, maltose, nicotinamide, urea). While the non-ionic cosolutes all destabilized the ligand/DNA complex, their quantitative effects were heterogeneous in a cosolute- and salt-dependent manner. Perturbation with NaCl in the absence of non-ionic cosolute showed that preferential hydration water was released upon formation of the DB1976/DNA complex. As salt probes counter-ion release from charged groups such as the DNA backbone, we propose that the preferential hydration uptake in DB1976/DNA binding observed in the presence of osmolytes reflects the exchange of preferentially bound cosolute with hydration water in the environs of the bound DNA, rather than a net uptake of hydration waters by the complex.
先前对模型小沟结合化合物与序列特异性DNA结合的研究表明，在存在兼容共溶质的情况下，配体/DNA复合物会变得不稳定。根据渗透应激理论，抑制作用被解释为复合物形成时从大量溶剂中摄取了大量多余的水分子。在这里，我们使用离子型（NaCl）和非离子型共溶质（乙二醇、甘氨酸甜菜碱、麦芽糖、烟酰胺、尿素），研究了与对称杂环二脒DB1976形成的AT特异性DNA复合物，作为小沟DNA识别的模型。虽然所有非离子型共溶质都会使配体/DNA复合物不稳定，但它们的定量效应在共溶质和盐依赖的方式上是异质的。在不存在非离子型共溶质的情况下用NaCl进行扰动表明，DB1976/DNA复合物形成时优先结合的水被释放。由于盐探针可探测从带电基团（如DNA主链）释放的抗衡离子，我们提出，在渗透剂存在下观察到的DB1976/DNA结合中优先摄取水合水，反映了结合的DNA周围优先结合的共溶质与水合水的交换，而不是复合物对水合水的净摄取。
