β3-tripeptides act as sticky ends to self-assemble into a bioscaffold

Peptides comprised entirely of beta(3)-amino acids, commonly referred to as beta-foldamers, have been shown to self-assemble into a range of materials. Previously, beta-foldamers have been functionalised via various side chain chemistries to introduce function to these materials without perturbation of the self-assembly motif. Here, we show that insertion of both rigid and flexible molecules into the backbone structure of the beta-foldamer did not disturb the self-assembly, provided that the molecule is positioned between two beta(3)-tripeptides. These hybrid beta(3)-peptide flanked molecules self-assembled into a range of structures. alpha-Arginlyglycylaspartic acid (RGD), a commonly used cell attachment motif derived from fibronectin in the extracellular matrix, was incorporated into the peptide sequence in order to form a biomimetic scaffold that would support neuronal cell growth. The RGD-containing sequence formed the desired mesh-like scaffold but did not encourage neuronal growth, possibly due to over-stimulation with RGD. Mixing the RGD peptide with a beta-fold amer without the RGD sequence produced a well-defined scaffold that successfully encouraged the growth of neurons and enabled neuronal electrical functionality. These results indicate that beta(3)-tripeptides can form distinct self-assembly units separated by a linker and can form fibrous assemblies. The linkers within the peptide sequence can be composed of a bioactive alpha-peptide and tuned to provide a biocompatible scaffold. (C) 2018 Author (s).