Anion-Selective Channels Formed by Synthetic 13-Mer Chimeric α -Peptide-Oligourea Foldamers

Area of Science:

• Supramolecular chemistry
• Biomaterials science
• Chemical biology

Background:

• Designing transmembrane channels with selective transport remains challenging.
• Previous work demonstrated α-peptide-oligourea foldamers forming anion channels with high chloride selectivity.

Purpose of the Study:

• To design and synthesize new α-peptide-oligourea chimeric foldamers with distinct hydrophobic and hydrophilic surfaces.
• To investigate their self-assembly into supramolecular channels and their ion transport properties.

Main Methods:

• Design and synthesis of four 13-mer chimeric foldamers (HPU-EK, HPU-QQ, HPU-AA, HPU-RH).
• Cryo-electron microscopy (cryo-EM) to determine structural features.
• Functional assays to evaluate anion transport activity and selectivity across lipid bilayer membranes.

Main Results:

• The foldamers self-assembled into supramolecular channels.
• Cryo-EM revealed nanofibers with diverse assembly modes for HPU-AA.
• HPU-AA exhibited the highest ion transport activity and selective anion transport (I⁻>SCN⁻>NO₃⁻ = Cl⁻>Br⁻>OAc⁻>F⁻).
• Mutations enhanced ion transport activity.

Conclusions:

• Chimeric foldamers can self-assemble into functional supramolecular channels.
• HPU-AA demonstrates significant potential for selective anion transport.
• These findings advance the understanding of foldamer self-assembly and offer opportunities for designing novel channels for biomedical applications.