Interfacial Self-Assembly of Antimicrobial Peptide GL13K into Non-Fibril Crystalline β-Sheets.

The need for new and potent antibiotics in an era of increasing multidrug resistance in bacteria has driven the search for new antimicrobial agents, including the design of synthetic antimicrobial peptides (AMPs). While a number of β-sheet forming AMPs have been proposed, their similarity to β-amyloids raises a number of concerns associated with neurodegenerative states. GL13K is an effective, synthetic AMP that selectively folds into β-sheets at anionic interfaces. Moreover, it is one of relatively few AMPs that preferentially fold into β-sheets without bridging disulfides. The interfacial activity of GL13K and its propensity to form amyloid fibrils have not been investigated. Using structural studies at the air/water interface and in the absence of anionic lipids, we demonstrate that while GL13K does form crystalline β-sheets, it does not self-assemble into fibrils. This work emphasizes the requirement for a single charged amino acid in the hydrophobic face to prevent fibril formation in synthetic peptides.