title: Minimalist synthetic host with stacked guanidinium ions mimics the weakened hydration shells of protein-protein interaction interfaces.
abstract: 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.
authors: Department of Chemistry, University of Victoria , P.O. Box 3600, Victoria V8W 3V6, Canada.
authors: Xing
authors: X
authors: Wang
authors: Joshua
authors: J
authors: Post
authors: Dennis K
authors: DK
authors: Hore
authors: Fraser
authors: F
authors: Hof
mesh_terms: D019791:Guanidine / Q000737:chemistry*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007477:Ions / Q000737:chemistry*; D054730:Protein Interaction Domains and Motifs; D012997:Solvents / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D007477:Ions; D012997:Solvents; D014867:Water; D019791:Guanidine