Minimalist Synthetic Host with Stacked Guanidinium Ions Mimics the Weakened Hydration Shells of Protein–protein Interaction Interfaces

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• 作者：Xing Wang ; Joshua Post ; Dennis K. Hore ; Fraser Hof
• 刊名：Journal of Organic Chemistry
• 出版年：2014
• 出版时间：January 3, 2014
• 年：2014
• 卷：79
• 期：1
• 页码：34-40
• 全文大小：335K
• ISSN：1520-6904

文摘

Protein surfaces are complex solutes, and protein鈥損rotein 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鈥損rotein 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鈥搘ater hydrogen bonds, a decrease in the density of water around the host, and a decrease in water鈥搘ater 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.