Fibrillisation of hydrophobically modified amyloid peptide fragments in an organic solvent

The self-assembly of a hydrophobically modified fragment of the amyloid beta(A beta) peptide has been studied in methanol. The peptide FFKLVFF is based on A beta(16-20) extended at the N terminus by two phenylalanine residues. The formation of amyloid-type fibrils is confirmed by Congo Red staining, thioflavin T fluorescence and circular dichroism experiments. FTIR points to the formation of beta-sheet structures in solution and in dried films and suggests that aggregation occurs at low concentration and is not strongly affected by further increase in concentration, i.e. the peptide is a strong fibril-former in methanol. UV fluorescence experiments on unstained peptide and CD point to the importance of aromatic interactions between phenylalanine groups in driving aggregation into beta-sheets. The CD spectrum differs from that usually observed for beta-sheet assemblies formed by larger peptides or proteins and this is discussed for solutions in methanol and also trifluoroethanol. The fibril structure is imaged by transmission electron microscopy and scanning electron microscopy on dried samples and is confirmed by small-angle X-ray scattering experiments in solution

Surface structure of thin asymmetric PS-b-PMMA diblock copolymers investigated by atomic force microscopy

Asymmetric poly(styrene-b-methyl methacrylate) (PS-b-PMMA) diblock copolymers of molecular weight M-n = 29,700g mol(-1) (M-PS = 9300 g mol(-1) M-PMMA = 20,100 g mol(-1), PD = 1.15, chi(PS) = 0.323, chi(PMMA) = 0.677) and M-n = 63,900 g mol(-1) (M-PS = 50,500 g mol(-1), M-PMMA = 13,400 g mol(-1), PD = 1.18, chi(PS) = 0.790, chi(PMMA) = 0.210) were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. Atomic force microscopy (AFM) was used to investigate the surface structure of thin films, prepared by spin-coating the diblock copolymers on a silicon substrate. We show that the nanostructure of the diblock copolymer depends on the molecular weight and volume fraction of the diblock copolymers. We observed a perpendicular lamellar structure for the high molar mass sample and a hexagonal-packed cylindrical patterning for the lower molar mass one. Small-angle X-ray scattering investigation of these samples without annealing did not reveal any ordered structure. Annealing of PS-b-PMMA samples at 160 degrees C for 24 h led to a change in surface structure

Self-assembly of peptide bioconjugates: selected recent research highlights

This Topical Review briefly discusses selected highlights of recent research on self-assembling peptide amphiphiles (PAs) and polymer–peptide conjugates. Subjects covered include new polymer chemistries used to prepare polymer–peptide conjugates, PA self-assembly landscapes and kinetics, developments in the application of bioactive PAs and the relationship between self-assembly and bioactivity, novel PA/biopolymer composites, functional π-stacking peptide conjugates, use of enzymes to tune self-assembly, and developments in high throughput methods and the design and application of sequenced peptides

Silica templating of a self-assembling peptide amphiphile that forms nanotapes

The peptide amphiphile C16-KTTKS templates silica polymerization, enabling the production of silica nanotape structures, imaged via electron microscopy (TEM and SEM). X-ray scattering shows that the nanotapes comprise stacked layers, as for the parent peptide amphiphile, but with a substantially increased layer spacing resulting from silica polymerization

Structure variation and evolution in microphase-separated grafted diblock copolymer films

The phase behavior of grafted d-polystyrene-block-poly(methyl methacrylate) diblock copolymer films is examined, with particular focus on the effect of solvent and annealing time. It was observed that the films undergo a two-step transformation from an initially disordered state, through an ordered metastable state, to the final equilibrium configuration. It was also found that altering the solvent used to wash the films, or complete removal of the solvent prior to thermal annealing using supercritical CO2, could influence the structure of the films in the metastable state, though the final equilibrium state was unaffected. To aid in the understanding to these experimental results, a series of self-consistent field theory calculations were done on a model diblock copolymer brush containing solvent. Of the different models examined, those which contained a solvent selective for the grafted polymer block most accurately matched the observed experimental behavior. We hypothesize that the structure of the films in the metastable state results from solvent enrichment of the film near the film/substrate interface in the case of films washed with solvent or faster relaxation of the nongrafted block for supercritical CO2 treated (solvent free) films. The persistence of the metastable structures was attributed to the slow reorganization of the polymer chains in the absence of solvent

Modulating self-assembly of a nanotape-forming peptide amphiphile with an oppositely charged surfactant

A peptide amphiphile (PA) C16-KTTKS, containing a pentapeptide headgroup based on a sequence from procollagen I attached to a hexadecyl lipid chain, self-assembles into extended nanotapes in aqueous solution. The tapes are based on bilayer structures, with a 5.2 nm spacing. Here, we investigate the effect of addition of the oppositely charged anionic surfactant sodium dodecyl sulfate (SDS) via AFM, electron microscopic methods, small-angle X-ray scattering and X-ray diffraction among other methods. We show that addition of SDS leads to a transition from tapes to fibrils, via intermediate states that include twisted ribbons. Addition of SDS is also shown to enhance the development of remarkable lateral ‘‘stripes’’ on the nanostructures, which have a 4 nm periodicity. This is ascribed to counterion condensation. The transition in the nanostructure leads to changes in macroscopic properties, in particular a transition from sol to gel is noted on increasing SDS (with a further reentrant transition to sol on further increase of SDS concentration). Formation of a gel may be useful in applications of this PA in skincare applications and we show that this can be controlled via development of a network of fine stranded fibrils

Beyond hierarchical order in biomimetic and liquid crystalline block copolymers

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Lipopeptides for vaccine development

The development of lipopeptides (lipidated peptides) for vaccines is discussed, including their role as antigens and/or adjuvants. Distinct classes of lipopeptide architectures are covered including simple linear and ligated constructs and lipid core peptides. The design, synthesis, and immunological responses of the important class of glycerol-based Toll-like receptor agonist lipopeptides such as Pam3CSK4, which contains three palmitoyl chains and a CSK4 hexapeptide sequence, and many derivatives of this model immunogenic compound are also reviewed. Self-assembled lipopeptide structures including spherical and worm-like micelles that have been shown to act as vaccine agents are also described. The work discussed includes examples of lipopeptides developed with model antigens, as well as for immunotherapies to treat many infectious diseases including malaria, influenza, hepatitis, COVID-19, and many others, as well as cancer immunotherapies. Some of these have proceeded to clinical development. The research discussed highlights the huge potential of, and diversity of roles for, lipopeptides in contemporary and future vaccine development

Biocatalysts based on peptide and peptide conjugate nanostructures

Peptides and their conjugates (to lipids, bulky N-terminals, or other groups) can self-assemble into nanostructures such as fibrils, nanotubes, coiled coil bundles, and micelles, and these can be used as platforms to present functional residues in order to catalyze a diversity of reactions. Peptide structures can be used to template catalytic sites inspired by those present in natural enzymes as well as simpler constructs using individual catalytic amino acids, especially proline and histidine. The literature on the use of peptide (and peptide conjugate) α-helical and β-sheet structures as well as turn or disordered peptides in the biocatalysis of a range of organic reactions including hydrolysis and a variety of coupling reactions (e.g., aldol reactions) is reviewed. The simpler design rules for peptide structures compared to those of folded proteins permit ready ab initio design (minimalist approach) of effective catalytic structures that mimic the binding pockets of natural enzymes or which simply present catalytic motifs at high density on nanostructure scaffolds. Research on these topics is summarized, along with a discussion of metal nanoparticle catalysts templated by peptide nanostructures, especially fibrils. Research showing the high activities of different classes of peptides in catalyzing many reactions is highlighted. Advances in peptide design and synthesis methods mean they hold great potential for future developments of effective bioinspired and biocompatible catalysts

Self-assembly, bioactivity, and nanomaterials applications of peptide conjugates with bulky aromatic terminal groups

The self-assembly and structural and functional properties of peptide conjugates containing bulky terminal aromatic substituents are reviewed with a particular focus on bioactivity. Terminal moieties include Fmoc [fluorenylmethyloxycarbonyl], naphthalene, pyrene, naproxen, diimides of naphthalene or pyrene, and others. These provide a driving force for self-assembly due to π-stacking and hydrophobic interactions, in addition to the hydrogen bonding, electrostatic, and other forces between short peptides. The balance of these interactions leads to a propensity to self-assembly, even for conjugates to single amino acids. The hybrid molecules often form hydrogels built from a network of β-sheet fibrils. The properties of these as biomaterials to support cell culture, or in the development of molecules that can assemble in cells (in response to cellular enzymes, or otherwise) with a range of fascinating bioactivities such as anticancer or antimicrobial activity, are highlighted. In addition, applications of hydrogels as slow-release drug delivery systems and in catalysis and other applications are discussed. The aromatic nature of the substituents also provides a diversity of interesting optoelectronic properties that have been demonstrated in the literature, and an overview of this is also provided. Also discussed are coassembly and enzyme-instructed self-assembly which enable precise tuning and (stimulus-responsive) functionalization of peptide nanostructures