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.
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.
Institute for Organic Chemistry, University of Duisburg-Essen, 45117, Essen, Germany.
Poulami
P
Jana
Institute for Organic Chemistry, University of Duisburg-Essen, 45117, Essen, Germany.
Martin
M
Ehlers
Institute for Organic Chemistry, University of Duisburg-Essen, 45117, Essen, Germany.
Elio
E
Zellermann
Institute for Organic Chemistry, University of Duisburg-Essen, 45117, Essen, Germany.
Krishnananda
K
Samanta
Institute for Organic Chemistry, University of Duisburg-Essen, 45117, Essen, Germany.
Carsten
C
Schmuck
D000682:Amyloid / Q000138:chemical synthesis* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013501:Surface-Active Agents / Q000737:chemistry*
D000682:Amyloid; D010455:Peptides; D013501:Surface-Active Agents
amyloid fiber; nanostructures; secondary structures; self-assembly; β-sheets