Modulation of Antimicrobial Peptide Conformation and Aggregation by Terminal Lipidation and Surfactants.

The function and properties of peptide-based materials depend not only on the amino acid sequence but also on the molecular conformations. In this paper, we chose a series of peptides G(XXKK)X-NH ( = 0, 3; = 2, 3; X = I, L, and V) as the model molecules and studied the conformation regulation through N-terminus lipidation and their formulation with surfactants. The structural and morphological transition of peptide self-assemblies have also been investigated via transmission electron microscopy, atomic force microscopy, circular dichroism spectroscopy, and small-angle neutron scattering. With the terminal alkylation, the molecular conformation changed from random coil to β-sheet or α-helix. The antimicrobial activities of alkylated peptide were different. C-G(IIKK)I-NH showed antimicrobial activity against while C-(IIKK)I-NH and C-G(IIKK)I-NH did not kill the bacteria. The surfactant sodium dodecyl sulfonate could rapidly induce the self-assemblies of alkylated peptides (C-(IIKK)I-NH, C-G(IIKK)I-NH, C-G(VVKK)V-NH) from nanofibers to micelles, along with the conformation changing from β-sheet to α-helix. The cationic surfactant hexadecyl trimethyl ammonium bromide made the lipopeptide nanofibers thinner, and nonionic surfactant polyoxyethylene (23) lauryl ether (CEO) induced the nanofibers much more intensively. Both the activity and the conformation of the α-helical peptide could be modulated by lipidation. Then, the self-assembled morphologies of alkylated peptides could also be further regulated with surfactants through hydrophobic, electrostatic, and hydrogen-bonding interactions. These results provided useful strategies to regulate the molecular conformations in peptide-based material functionalization.