PH-Controlled Formation of a Stable β-Sheet and Amyloid-like Fibers from an Amphiphilic Peptide: The Importance of a Tailor-Made Binding Motif for Secondary Structure Formation.

Abstract

The new amphiphilic peptide 1 is composed of alternating cyclohexyl side chains and guanidiniocarbonyl pyrrole (GCP) groups. In contrast to analogue 2, which contains lysine instead of the GCP groups and only exists as a random coil owing to charge repulsion, peptide 1 forms a stable β-sheet at neutral pH in aqueous medium. The weakly basic GCP groups (pKa ≈7) are key for secondary structure formation as they stabilize the β-sheet through mutual interactions (formation of a "GCP zipper"). The β-sheets further aggregate into left-handed helically twisted fibers. However, β-sheet formation is completely reversible as a function of pH. At low pH (ca. 4), peptide 1 is unstructured (random coil) as all GCP units are protonated. Only round colloidal particles are observed. The amyloid nature of the fibers formed at neutral pH was confirmed by staining experiments with Congo Red and thioflavin T. Furthermore, at millimolar concentrations, peptide 1 forms a stable hydrogel.