Metal-Directed Self-Assembly of Minimal Heterochiral Peptides into Metallo-Supramolecular β-Helical Tubules for Artificial Transmembrane Water Channels

Abstract

Transmembrane selective transport of metabolites controls essential biological functions. During the last two decades, artificial channels have been developed and cyclic peptides have emerged as ideal platforms for efficient ion, sugar, and nucleic acid channel translocation. Despite these tremendous developments, cyclic peptides have eluded selective water transport. Herein, we report the formation of narrow artificial β-helical tubules with diameters ranging from 2.80 to 3.25 Å that selectively control the water translocation, akin to natural aquaporin channels. The tubular assemblies resulted from the metal-driven folding and assembly of minimal heterochiral metal-binding 3-pyridyl-terminated peptides. The bent ultrashort peptide ligand coordinates with Ag+ metal ions in a head-to-tail manner, which undergoes subsequent polymerization into a β-helical tubular structure stabilized by interstrand hydrogen bonds (H-bonds) between the β-strands and π–π staking interactions between terminal pyridyl moieties. Furthermore, sequence engineering of the heterochiral peptide and subsequent Ag+ ion coordination of the tailored peptides enabled the formation of distinct synthetic double β-barrel and artificial β-helical tubular assemblies, with water molecules encapsulated in the hydrophilic core of the tubes. These water-encapsulated tubes were further explored as artificial water channels in lipid bilayers. Our findings suggest that such β-helical tubular channels achieve a single-channel permeability of 106 water molecules/second/channel, which is within 1-2 orders of magnitude lower than that of aquaporins, with a rather good ability to sterically reject ions and prevent proton transport. These assemblies present significant potential for engineering efficient membranes for water purification and separation sciences.