Highly Selective Bioinspired Peptide Channels for Rapid Water Transport

Innovative water-purification technologies are urgently needed to address the global scarcity of clean water. In nature, aquaporin proteins enable rapid and highly selective water transport across membranes. Replicating their exceptional water flux and ion-rejection capabilities in synthetic systems, however, remains a major challenge. Herein, minimalistic peptide-based water-channels inspired by the conserved aquaporin Asn-Pro-Ala (NPA) motif are reported. These designer peptides are suitably functionalized to enable the formation of water-channels by self-assembly. The crystal structures of these water channels highlight how inward-facing polar groups facilitate water transport, while hydrophobic exteriors enable membrane interactions. Channels derived from functionalized PA dipeptides and a tripeptide NPA analog with a pendant cyano group exhibit exceptional single-channel permeabilities (≈10⁸ H₂O s^-1 channel^-1). While both peptides achieve complete Na⁺, Cl^-, and proton exclusion, the NPA tripeptide shows marginal (∼10%) K⁺ transport. Molecular dynamics simulations, x-ray structures, and experimentally determined activation energies suggest a water-transport mechanism involving hydrogen-bonding interactions with the peptide-backbone. This work illustrates how structurally simple peptides can accomplish highly efficient and selective water transport, paving the way for compact and tunable molecular platforms for water-purification and biomedical applications.