Self-Assembling Cyclic β3-Peptide Nanotubes as Artificial Transmembrane Ion Channels

Abstract

A new class of self-assembling transmembrane ion channels based on cyclic β 3 -peptides is described. Cyclic peptide subunits were designed to adopt flat, ring shaped conformations and stack through extensive backbone-backbone hydrogen bonding to form tubular channel structures. Candidate channel-forming peptides cyclo [(-β 3 -HTrp) 4 -] 1, cyclo [(-β 3 -HTrp-β-HLeu) 2 -] 2, and cyclo [(-β 3 -HLeu) 4 -] 3 were examined in liposome-based proton transport assays and single channel conductance experiments. Compounds 1 and 2 exhibited remarkable ion transport activities with single-channel K + conductance of 56 pS for peptide 1, while compound 3 was inactive, possibly due to its poor solubility. Additionally, the putative structure of transmembrane channels formed by peptides 1 and 2 was supported by FT-IR spectroscopy of membrane-peptide preparations. The present system not only complements that of channel-forming cyclic d, l -α-peptides previously reported from this laboratory but also is expected to exhibit novel properties arising from the unnatural β 3 -peptide backbone.