Self-assembling peptides offer a versatile set of tools for bottom-up construction
of supramolecular biomaterials. Among these compounds, non-natural peptidic foldamers
experience increased focus due to their structural variability and lower sensitivity
to enzymatic degradation. However, very little is known about their membrane properties
and complex oligomeric assemblies - key areas for biomedical and technological applications.
Here we designed short, acyclic beta(3)-peptide sequences with alternating amino acid
stereoisomers to obtain non-helical molecules having hydrophilic charged residues
on one side, and hydrophobic residues on the other side, with the N-terminus preventing
formation of infinite fibrils. Our results indicate that these beta-peptides form
small oligomers both in water and in lipid bilayers and are stabilized by intermolecular
hydrogen bonds. In the presence of model membranes, they either prefer the headgroup
regions or they insert between the lipid chains. Molecular dynamics (MD) simulations
suggest the formation of two-layered bundles with their side chains facing opposite
directions when compared in water and in model membranes. Analysis of the MD calculations
showed hydrogen bonds inside each layer, however, not between the layers, indicating
a dynamic assembly. Moreover, the aqueous form of these oligomers can host fluorescent
probes as well as a hydrophobic molecule similarly toe.g.lipid transfer proteins.
For the tested, peptides the mixed chirality pattern resulted in similar assemblies
despite sequential differences. Based on this, it is hoped that the presented molecular
framework will inspire similar oligomers with diverse functionality.
