Membrane active Janus-oligomers of β³-peptides

Area of Science:

• Supramolecular chemistry
• Biomaterials science
• Peptide engineering

Background:

• Self-assembling peptides are crucial for bottom-up biomaterial construction.
• Non-natural peptidic foldamers offer structural diversity and enzymatic stability.
• Understanding their membrane properties and assembly is vital for applications.

Purpose of the Study:

• To design and investigate the membrane properties and oligomeric assemblies of short, acyclic β3-peptides.
• To explore the influence of alternating stereoisomers and residue types on peptide assembly.
• To assess the potential of these peptides for hosting molecules.

Main Methods:

• Design of acyclic β3-peptide sequences with alternating stereoisomers and distinct hydrophilic/hydrophobic residues.
• Experimental investigation of peptide oligomerization in aqueous and lipid bilayer environments.
• Molecular dynamics (MD) simulations to elucidate assembly mechanisms and structural dynamics.

Main Results:

• Designed β-peptides form small, stable oligomers in water and lipid bilayers, stabilized by intermolecular hydrogen bonds.
• Peptides interact with model membranes by associating with headgroups or inserting into lipid chains.
• MD simulations reveal dynamic two-layered bundle formation with side chains oriented outwards, with intra-layer hydrogen bonding.

Conclusions:

• Acyclic β3-peptides with mixed chirality self-assemble into small, dynamic oligomers with predictable membrane interactions.
• These peptide assemblies can encapsulate various molecules, suggesting potential as biomimetic carriers.
• The designed molecular framework provides a basis for developing functional supramolecular biomaterials.