Self-assembly of carbamylated lysine repeat peptide amphiphiles into fibrillar nanostructures

Abstract

Peptide amphiphilicity enables self-assembly, forming well-defined structures such as micelles and polymersomes. The exploration of hydrophilic lysine-rich peptides with hydrophobic lipid modifications at the N-terminus to form self-assembling peptide amphiphiles as a strategy is explored in this study. Carbamylation, a post-translational modification known to promote the aggregation of proteins, reported in neurodegenerative disorders, is exploited for charge neutralization of lysine residues, thereby inducing amyloidogenicity in peptides. In our study, we synthesized a series of lysine repeat peptides (3K, 5K, and 8K) of variable lengths with a combination of hydrophobic tailing (C2, C6, and C9) as models using SPPS (solid-phase peptide synthesis). The amyloidogenic properties of carbamylated lysine peptides, including aggregation kinetics, were studied through several assays to assess the structural and functional implications of carbamylation on self-assembling peptide amphiphiles. We also compared the morphological similarities and differences using microscopic imaging techniques, such as bright-field, fluorescence, and scanning electron microscopy, to visualize and characterize the fibrillar assembly across these model peptides. The synthesized self-assembling amphiphiles can be tuned for use in various applications, including drug delivery carrier development, tissue engineering, antifouling, antifogging, and dye degradation modality.