Membrane active Janus-oligomers of β3-peptides
Journal article, 2020
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 β3-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 β-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 to e.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.
Molecular dynamics
Peptides
Molecules
Hydrophobicity
Stereochemistry
Complexation
Lipid bilayers
Hydrogen bonds
Author
Imola Cs Szigyártó
Hungarian Research Network
Judith Mihály
Hungarian Research Network
András Wacha
Hungarian Research Network
Dóra Bogdán
Hungarian Research Network
Semmelweis University
Tünde Juhász
Hungarian Research Network
Gergely Kohut
Hungarian Research Network
Eötvös Loránd University (ELTE)
Gitta Schlosser
Eötvös Loránd University (ELTE)
Ferenc Zsila
Hungarian Research Network
Vlada Urlacher
Heinrich Heine University Düsseldorf
Zoltán Varga
Hungarian Research Network
Ferenc Fülöp
University of Szeged / Szegedi Tudományegyetem
Attila Bóta
Hungarian Research Network
István Mándity
Hungarian Research Network
Semmelweis University
Tamas Beke-Somfai
Hungarian Research Network
Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry
Chemical Science
2041-6520 (ISSN) 2041-6539 (eISSN)
Vol. 11 26 6868-6881Subject Categories (SSIF 2011)
Physical Chemistry
Biochemistry and Molecular Biology
Biophysics
Areas of Advance
Health Engineering
Materials Science
DOI
10.1039/d0sc01344g