1.D.151.  The Aromatic Amphipathic α-helical Peptide-Ion Channel (AAAP-IC) Family 

Aromatic interactions such as pi-pi and cation-pi interactions are present in membrane proteins and play important roles in both structure and function. The effects of aromatic residues (one or two tryptophan residues in different positions) on the structural stability and ion permeability of peptide-formed ion channels were designed (Shigedomi et al. 2021). Trp residues played roles in self-association of the peptides. Peptides with two Trps at each helix termini allowing intermolecular Trp-Trp interactions caused aggregation. In liposomes, Trp on the hydrophilic face of the peptide enhanced interaction with the lipid membrane to increase the amphipathic alpha-helical contents. Appropriate incorporation and positioning of Trp enabled peptides to form more stable channels.  The ion channel forming capability of a series of these peptides showed that cation-pi interactions between Trp and Lys residues in adjacent transmembrane helices stabilized the channel structure (Shigedomi et al. 2021).  α-helical amphiphilic peptides often have the ability to (1) translocate across phospholipid bilayers, (2) form transmembrane pores, or (3) act synergistically, i.e., to produce significantly more potent effects in a mixture than the individual components by themselves (Kabelka and Vácha 2021).



Kabelka, I. and R. Vácha. (2021). Advances in Molecular Understanding of α-Helical Membrane-Active Peptides. Acc Chem Res 54: 2196-2204.

Shigedomi, K., S. Osada, M. Jelokhani-Niaraki, and H. Kodama. (2021). Systematic Design and Validation of Ion Channel Stabilization of Amphipathic α-Helical Peptides Incorporating Tryptophan Residues. ACS Omega 6: 723-732.