Novel Materials From the Supramolecular Self-Assembly of Short Helical β3-Peptide Foldamers

Self-assembly is the spontaneous organization of small components into higher-order structures facilitated by the collective balance of non-covalent interactions. Peptide-based self-assembly systems exploit the ability of peptides to adopt distinct secondary structures and have been used to produce a range of well-defined nanostructures, such as nanotubes, nanofibres, nanoribbons, nanospheres, nanotapes, and nanorods. While most of these systems involve self-assembly of α-peptides, more recently β-peptides have also been reported to undergo supramolecular self-assembly, and have been used to produce materials—such as hydrogels—that are tailored for applications in tissue engineering, cell culture and drug delivery. This review provides an overview of self-assembled peptide nanostructures obtained via the supramolecular self-assembly of short β-peptide foldamers with a specific focus on N-acetyl-β3-peptides and their applications as bio- and nanomaterials

Transition of nano-architectures through self-assembly of lipidated β3-tripeptide foldamers

β3-peptides consisting exclusively of β3-amino acids adopt a variety of non-natural helical structures and can self-assemble into well-defined hierarchical structures by axial head-to-tail self-assembly resulting in fibrous materials of varying sizes and shapes. To allow control of fiber morphology, a lipid moiety was introduced within a tri-β3-peptide sequence at each of the three amino acid positions and the N-terminus to gain finer control over the lateral assembly of fibers. Depending on the position of the lipid, the self-assembled structures formed either twisted ribbon-like fibers or distinctive multilaminar nanobelts. The nanobelt structures were comprised of multiple layers of peptide fibrils as revealed by puncturing the surface of the nanobelts with an AFM probe. This stacking phenomenon was completely inhibited through changes in pH, indicating that the layer stacking was mediated by electrostatic interactions. Thus, the present study is the first to show controlled self-assembly of these fibrous structures, which is governed by the location of the acyl chain in combination with the 3-point H-bonding motif. Overall, the results demonstrate that the nanostructures formed by the β3-tripeptide foldamers can be tuned via sequential lipidation of N-acetyl β3-tripeptides which control the lateral interactions between peptide fibrils and provide defined structures with a greater homogeneous population

Internalisation of the mu-opioid receptor by endomorphin-1 and leu-enkephalin is dependant on aromatic amino acid residues

The opioid receptor system in the central nervous system controls a number of physiological processes, most notably pain. However, most opioids currently available have a variety of side-effects as well as exhibiting tolerance. Tolerance is most likely to be a complex phenomenon, however, the role of receptor internalisation is thought to play a crucial role. In this study, we examined the role of aromaticity in ligand-mediated receptor internalisation of the μ-opioid receptor (MOPR). These studies show that the amount of receptor internalisation may be dependant on the amphiphilicity of the ligand. Specifically, deletion of the C-terminus aromatic residues of endomorphin 1, particularly tryptophan reduces receptor-mediated internalisation whilst the addition of tryptophan within the enkephalin sequence increases receptor internalisation and decreases tolerance

Shortened Penetratin Cell-Penetrating Peptide Is Insufficient for Cytosolic Delivery of a Grb7 Targeting Peptide

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

Peptides comprised entirely of β3-amino acids, commonly referred to as β-foldamers, have been shown to self-assemble into a range of materials. Previously, β-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 β-foldamer did not disturb the self-assembly, provided that the molecule is positioned between two β3-tripeptides. These hybrid β3-peptide flanked molecules self-assembled into a range of structures. α-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 β-foldamer 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 β3-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 α-peptide and tuned to provide a biocompatible scaffold

Migration and Differentiation of Neural Stem Cells Diverted From the Subventricular Zone by an Injectable Self-Assembling β-Peptide Hydrogel

Neural stem cells, which are confined in localised niches are unable to repair large brain lesions because of an inability to migrate long distances and engraft. To overcome these problems, previous research has demonstrated the use of biomaterial implants to redirect increased numbers of endogenous neural stem cell populations. However, the fate of the diverted neural stem cells and their progeny remains unknown. Here we show that neural stem cells originating from the subventricular zone can migrate to the cortex with the aid of a long-lasting injectable hydrogel within a mouse brain. Specifically, large numbers of neuroblasts were diverted to the cortex through a self-assembling β-peptide hydrogel that acted as a tract from the subventricular zone to the cortex of transgenic mice (NestinCreERT2:R26eYFP) in which neuroblasts and their progeny are permanently fluorescently labelled. Moreover, neuroblasts differentiated into neurons and astrocytes 35 days post implantation, and the neuroblast-derived neurons were Syn1 positive suggesting integration into existing neural circuitry. In addition, astrocytes co-localised with neuroblasts along the hydrogel tract, suggesting that they assisted migration and simulated pathways similar to the native rostral migratory stream. Lower levels of astrocytes were found at the boundary of hydrogels with encapsulated brain-derived neurotrophic factor, comparing with hydrogel implants alone