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

Abstract

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_<i>m</i>(XXKK)_<i>n</i>X-NH₂ (<i>m</i> = 0, 3; <i>n</i> = 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. C₁₆-G₃(IIKK)₃I-NH₂ showed antimicrobial activity against <i>Streptococcus mutans,</i> while C₁₆-(IIKK)₂I-NH₂ and C₁₆-G₃(IIKK)₂I-NH₂ did not kill the bacteria. The surfactant sodium dodecyl sulfonate could rapidly induce the self-assemblies of alkylated peptides (C₁₆-(IIKK)₂I-NH₂, C₁₆-G₃(IIKK)₂I-NH₂, C₁₆-G₃(VVKK)₂V-NH₂) 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 (C₁₂EO₂₃) 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.