1.D.312.  The Chimeric α-Peptide-Oligourea Foldamer-Chloride Channel (POF-CC) Family

Transmembrane ion channels made up of amphiphilic peptide-oligourea chimeric helices have been develooped. They consist of an oligourea segment (7-mer) attached to the C-terminus of a short peptide (8-mer). Mass spectrometry (MS) and transmission electron microscopy (TEM) analyses showed that in an aqueous solution, two of these chimeras (HPU-E and HPU-N) independently formed defined oligomeric structures. TEM also showed that they form fiber bundles. The third related chimera, HPU-F, did not oligomerize (MS) but formed spherical nanostructures (TEM). HPU-E and HPU-N exhibit anion transport activities across lipid bilayers via an antiport mechanism (HPU-N > HPU-E). The anion selectivity of HPU-N is Cl^- > NO₃^- > Br^- > SCN^- > I^- > AcO^- > F^-, which can be due to anion binding within the channels rather than size exclusion. Patch-clamp data supported HPU-N's Cl^- selectivity (PCl^-/PI^- = 3.26). X-ray crystal structure (1.77 Å) of HPU-N reveals well-packed α-helices, and cryo-electron microscopy data showed the formation of nanotubes (13.7 Å diameter pores) and transmembrane channels (Dutta et al. 2024).