Department of Chemistry, University of Victoria , P.O. Box 3600, Victoria V8W 3V6, Canada.
J Org Chem. 2014 Jan 3;79(1):34-40. doi: 10.1021/jo401949s. Epub 2013 Dec 18.
Protein surfaces are complex solutes, and protein-protein interactions are specifically mediated by surface motifs that modulate solvation shells in poorly understood ways. We report herein a supramolecular host that is designed to mimic one of the most important recognition motifs that drives protein-protein interactions, the stacked arginine side chain. We show that it binds its guests and displays good selectivity in the highly competitive medium of pure, buffered water. We use a combination of experimental studies of binding and molecular dynamics simulations to build a cohesive picture of how this biomimetic host achieves the feat. The presence of the stacking element next to the guanidinium groups causes a decrease in the number of host-water hydrogen bonds, a decrease in the density of water around the host, and a decrease in water-water hydrogen bonds near the host. Experimental data using mixed organic/aqueous solvent systems confirm that this host relies on the hydrophobic effect in a way that the two control hosts do not. Our simulations and analysis provide detailed information on the linkage between (de)hydration and binding events in water in a way that could be applied to many aqueous supramolecular systems.
蛋白质表面是复杂的溶质，而蛋白质-蛋白质相互作用则是通过表面模体特异性介导的，这些模体以人们知之甚少的方式调节溶剂化壳。我们在此报告了一种超分子主体，它旨在模拟驱动蛋白质-蛋白质相互作用的最重要识别模体之一，即堆积的精氨酸侧链。我们表明，它能够结合其客体，并在高度竞争的纯缓冲水溶液中表现出良好的选择性。我们结合结合实验研究和分子动力学模拟，构建了一幅连贯的图景，说明这种仿生主体如何实现这一壮举。堆积元件紧邻胍基的存在导致主体-水氢键数量减少、主体周围水的密度降低以及主体附近水-水氢键减少。使用混合有机/水溶剂系统的实验数据证实，这种主体依赖于疏水效应，而两种对照主体则没有。我们的模拟和分析提供了有关水合（去）水和结合事件之间联系的详细信息，这可以应用于许多水相超分子系统。
