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The human cardiac troponin C peptide fragment H-V9EQLTEEQKNEFKAAFDIFVLGA31-OH, which covers helix-A in the native protein, self-assembles into β-sheet fibrils in solution. These fibrils further entangle to give a hydrogel. This peptide may therefore serve as a template for development of novel biomaterials. [ABSTRACT FROM AUTHOR]

The self-assembly of the macrophage-activating lipopeptide MALP-2 in aqueous solution has been investigated and is compared to that of the constituent peptide GNNDESNISFKEK. MALP-2 is a toll-like receptor agonist lipopeptide with diverse potential biomedical applications and its self-assembly has not previously been examined. It is found to self-assemble, above a critical aggregation concentration (cac), into remarkable "fibre raft" structures, based on lateral aggregation of β-sheet based bilayer tapes. Peptide GNNDESNISFKEK also forms β-sheet structures above a cac, although the morphology is distinct, comprising highly extended and twisted tape structures. A detailed insight into the molecular packing within the MALP-2 raft and GNNDESNISFKEK nanotape structures is obtained through X-ray diffraction and small-angle X-ray scattering. These results point to the significant influence of the attached lipid chains on the self-assembly motif, which lead to the raft structure for the lipopeptide assemblies. [ABSTRACT FROM AUTHOR]

The self-assembly of peptide nanotubes formed by an l-glutamic acid-based bolaamphiphile is shown to proceed via a remarkable mechanism where the peptide conformation changes from β-sheet to unordered. The kinetics of this process are elucidated via X-ray scattering and UV circular dichroism methods. The reverse transition from “unordered” to β-sheet structures is triggered by UV radiation. [ABSTRACT FROM AUTHOR]

Abstract: The self-assembly and bioactivity of the peptide–polymer conjugate DGRFFF–PEG3000 containing the RGD cell adhesion motif has been examined, in aqueous solution. The conjugate is designed to be amphiphilic by incorporation of three hydrophobic phenylalanine residues as well as the RGD unit and a short poly(ethylene glycol) (PEG) chain of molar mass 3000kgmol−1. Above a critical aggregation concentration, determined by fluorescence measurements, signals of β-sheet structure are revealed by spectroscopic measurements, as well as X-ray diffraction. At high concentration, a self-assembled fibril nanostructure is revealed by electron microscopy. The fibrils are observed despite PEG crystallization which occurs on drying. This suggests that DGRFFF has an aggregation tendency that is sufficiently strong not to be prevented by PEG crystallization. The adhesion, viability and proliferation of human corneal fibroblasts was examined for films of the conjugate on tissue culture plates (TCPs) as well as low attachment plates. On TCP, DGRFFF–PEG3000 films prepared at sufficiently low concentration are viable, and cell proliferation is observed. However, on low attachment surfaces, neither cell adhesion nor proliferation was observed, indicating that the RGD motif was not available to enhance cell adhesion. This was ascribed to the core–shell architecture of the self-assembled fibrils with a peptide core surrounded by a PEG shell which hinders access to the RGD unit. [Copyright &y& Elsevier]

The self-assembly of three cosmeticallyactive peptide amphiphilesC16-GHK, C16-KT, and C16-KTTKS (C16denotes a hexadecyl, palmitoyl chain) used in commercialskin care products is examined. A range of spectroscopic, microscopic,and X-ray scattering methods is used to probe the secondary structure,aggregate morphology, and the nanostructure. Peptide amphiphile (PA)C16-KTTKS forms flat tapes and extended fibrillar structureswith high β-sheet content. In contrast, C16-KT andC16-GHK exhibit crystal-like aggregates with, in the caseof the latter PA, lower β-sheet content. All three PA samplesshow spacings from bilayer structures in small-angle X-ray scatteringprofiles, and all three have similar critical aggregation concentrations,this being governed by the lipid chain length. However, only C16-KTTKS is stained by Congo red, a diagnostic dye used todetect amyloid formation, and this PA also shows a highly alignedcross-β X-ray diffraction pattern consistent with the high β-sheetcontent in the self-assembled aggregates. These findings may provideimportant insights relevant to the role of self-assembled aggregateson the reported collagen-stimulating properties of these PAs. [ABSTRACT FROM AUTHOR]

Insulin-degrading enzyme (IDE) is a neutral Zn2+ peptidase that degrades short peptides based on substrate conformation, size and charge. Some of these substrates, including amyloid β (Aβ) are capable of self-assembling into cytotoxic oligomers. Based on IDE recognition mechanism and our previous report of the formation of a stable complex between IDE and intact Aβ in vitro and in vivo, we analyzed the possibility of a chaperone-like function of IDE. A proteolytically inactive recombinant IDE with Glu111 replaced by Gln (IDEQ) was used. IDEQ blocked the amyloidogenic pathway of Aβ yielding non-fibrillar structures as assessed by electron microscopy. Measurements of the kinetics of Aβ aggregation by light scattering showed that 1) IDEQ effect was promoted by ATP independent of its hydrolysis, 2) end products of Aβ-IDEQ co-incubation were incapable of “seeding” the assembly of monomeric Aβ and 3) IDEQ was ineffective in reversing Aβ aggregation. Moreover, Aβ aggregates formed in the presence of IDEQ were non-neurotoxic. IDEQ had no conformational effects upon insulin (a non-amyloidogenic protein under physiological conditions) and did not disturb insulin receptor activation in cultured cells. Our results suggest that IDE has a chaperone-like activity upon amyloid-forming peptides. It remains to be explored whether other highly conserved metallopeptidases have a dual protease-chaperone function to prevent the formation of toxic peptide oligomers from bacteria to mammals. [ABSTRACT FROM AUTHOR]

A strategy is presented that exploits the ability ofsyntheticpolymers of different nature to disturb the strong self-assembly capabilitiesof amyloid based β-sheet forming peptides. Following a convergentapproach, the peptides of interest were synthesized via solid-phasepeptide synthesis (SPPS) and the polymers via reversible addition–fragmentationchain transfer (RAFT) polymerization, followed by a copper(I) catalyzedazide–alkyne cycloaddition (CuAAC) to generate the desiredpeptide–polymer conjugates. This study focuses on a modifiedversion of the core sequence of the β-amyloid peptide (Aβ),Aβ(16–20) (KLVFF). The influence of attaching short poly(N-isopropylacrylamide) and poly(hydroxyethylacrylate) tothe peptide sequences on the self-assembly properties of the hybridmaterials were studied via infrared spectroscopy, TEM, circular dichroismand SAXS. The findings indicate that attaching these polymers disturbsthe strong self-assembly properties of the biomolecules to a certaindegree and permits to influence the aggregation of the peptides basedon their β-sheets forming abilities. This study presents aninnovative route toward targeted and controlled assembly of amyloid-likefibers to drive the formation of polymeric nanomaterials. [ABSTRACT FROM AUTHOR]

Studying peptide amphiphiles (PAs), we investigate theinfluenceof alkyl chain length on the aggregation behavior of the collagen-derivedpeptide KTTKS with applications ranging from antiwrinkle cosmeticcreams to potential uses in regenerative medicine. We have studiedsynthetic peptides amphiphiles C14–KTTKS (myristoyl-Lys-Thr-Thr-Lys-Ser)and C18–KTTKS (stearoyl-Lys-Thr-Thr-Lys-Ser) toinvestigate in detail their physicochemical properties. It is presumedthat the hydrophobic chain in these self-assembling peptide amphiphilesenhances peptide permeation across the skin compared to KTTKS alone.Subsequently Cn–KTTKS should actas a prodrug and release the peptide by enzymatic cleavage. Our resultsshould be useful in the further development of molecules with collagen-stimulatingactivity. [ABSTRACT FROM AUTHOR]

Abstract: There has been great interest recently in peptide amphiphiles and block copolymers containing biomimetic peptide sequences due to applications in bionanotechnology. We investigate the self-assembly of the peptide-PEG amphiphile FFFF-PEG5000 containing the hydrophobic sequence of four phenylalanine residues conjugated to PEG of molar mass 5000. This serves as a simple model peptide amphiphile. At very low concentration, association of hydrophobic aromatic phenylalanine residues occurs, as revealed by circular dichroism and UV/vis fluorescence experiments. A critical aggregation concentration associated with the formation of hydrophobic domains is determined through pyrene fluorescence assays. At higher concentration, defined β-sheets develop as revealed by FTIR spectroscopy and X-ray diffraction. Transmission electron microscopy reveals self-assembled straight fibril structures. These are much shorter than those observed for amyloid peptides, the finite length may be set by the end cap energy due to the hydrophobicity of phenylalanine. The combination of these techniques points to different aggregation processes depending on concentration. Hydrophobic association into irregular aggregates occurs at low concentration, well-developed β-sheets only developing at higher concentration. Drying of FFFF-PEG5000 solutions leads to crystallization of PEG, as confirmed by polarized optical microscopy (POM), FTIR and X-ray diffraction (XRD). PEG crystallization does not disrupt local β-sheet structure (as indicated by FTIR and XRD). However on longer lengthscales the β-sheet fibrillar structure is perturbed because spherulites from PEG crystallization are observed by POM. [Copyright &y& Elsevier]

A series of heptapeptides comprising the core sequence Aβ(16–20), KLVFF, of the amyloid β peptide coupled with paired N-terminal γ-amino acids are investigated in terms of cytotoxicity reduction and binding to the full Aβ peptide, both pointing to inhibition of fibrillisation for selected compounds. This is related to the self-assembly capacity of the heptapeptides. [ABSTRACT FROM AUTHOR]

The nanostructure of a peptide amphiphile in commercial use in anti-wrinkle creams is investigated. The peptide contains a matrikine, collagen-stimulating, pentapeptide sequence. Self-assembly into giant nanotapes is observed and the internal structure was found to comprise bilayers parallel to the flat tape surfaces. [ABSTRACT FROM AUTHOR]

The structure of single wall peptide nanotubes is presented for the model surfactant-like peptide A6K. Capillary flow alignment of a sample in the nematic phase at high concentration in water leads to oriented X-ray diffraction patterns. Analysis of these, accompanied by molecular dynamics simulations, suggests the favourable self-assembly of antiparallel peptide dimers into β-sheet ribbons that wrap helically to form the nanotube wall. [ABSTRACT FROM AUTHOR]

The structure of single wall peptide nanotubes is presented for the model surfactant-like peptide A6K. Capillary flow alignment of a sample in the nematic phase at high concentration in water leads to oriented X-ray diffraction patterns. Analysis of these, accompanied by molecular dynamics simulations, suggests the favourable self-assembly of antiparallel peptide dimers into β-sheet ribbons that wrap helically to form the nanotube wall. [ABSTRACT FROM AUTHOR]

Correction for ‘Self-assembly of the anti-fungal polyene amphotericin B into giant helically-twisted nanotapes’ by Ian William Hamley et al., Chem. Commun., 2015, 51, 17680–17683. [ABSTRACT FROM AUTHOR]

The self-assembly and bioactivity of a peptide amphiphile (PA) incorporating a 13-residue sequence derived from the last 13 amino acids of the C-terminus of lumican, C16-YEALRVANEVTLN, attached to a hexadecyl (C16) lipid chain have been examined. Lumican is a proteoglycan found in many types of tissue and is involved in collagen fibril organization. A critical aggregation concentration (cac) for the PA was determined through pyrene fluorescence measurements. The structure of the aggregates was imaged using electron microscopy, and twisted and curved nanotapes were observed. In situ small-angle X-ray scattering and fiber X-ray diffraction reveal that these tapes contain interdigitated bilayers of the PA molecules. FTIR and circular dichroism spectroscopy and fiber X-ray diffraction indicate that the lumican sequence in the PA adopts a β-sheet secondary structure. Cell assays using human dermal fibroblasts show that below the cac the PA displays good biocompatibility and also stimulates collagen production over a period of 3 weeks, exceeding a 2-fold enhancement for several concentrations. Thus, this PA has promise in future biological applications, in particular, in tissue engineering. [ABSTRACT FROM AUTHOR]

The bola-amphiphilic arginine-capped peptide RFL4RF self-assembles into nanotubes in aqueous solution. The nanostructure and rheology are probed by in situ simultaneous rheology/small-angle scattering experiments including rheo-SAXS, rheo-SANS, and rheo-GISANS (SAXS: small-angle X-ray scattering, SANS: small-angle neutron scattering, GISANS: grazing incidence small-angle neutron scattering). Nematic alignment of peptide nanotubes under shear is observed at sufficiently high shear rates under steady shear in either Couette or cone-and-plate geometry. The extent of alignment increases with shear rate. A shear plateau is observed in a flow curve measured in the Couette geometry, indicating the presence of shear banding above the shear rate at which significant orientation is observed (0.1-1 s-1). The orientation under shear is transient and is lost as soon as shear is stopped. GISANS shows that alignment at the surface of a cone-and-plate cell develops at sufficiently high shear rates, very similar to that observed in the bulk using the Couette geometry. A small isotope effect (comparing H2O/D2O solvents) is noted in the CD spectra indicating increased interpeptide hydrogen bonding in D2O, although this does not influence nanotube self-assembly. These results provide new insights into the controlled alignment of peptide nanotubes for future applications. [ABSTRACT FROM AUTHOR]

The surfactant-like peptide (Ala)6-(Asp) (A6D) is shown to self-assemble into ultrathin (3 nm thick) nanosheets in aqueous solution above a critical aggregation concentration. A combination of circular dichroism and FTIR spectroscopy and X-ray diffraction shows that the nanosheets comprise interdigitated bilayers of the peptide with β-sheet conformation. The self-assembly can be modulated by addition of hexamethylenediamine which is expected to interact with the anionic C terminus (and C-terminal D residue) of the peptide. Multiple ordered nanostructures can be accessed depending on the amount of added diamine. Nanosheet and bicontinuous network structures were observed using cryogenic-TEM and small-angle X-ray scattering. Addition of hexamethylenediamine at a sufficiently large molar ratio leads to disruption of the ordered nanostructure and the formation of a solution of A6D-diamine molecular complexes with highly charged end groups. The multiple acid-functionalized nanostructures that are accessible in this system are expected to have many applications in the fabrication of new nanomaterials. [ABSTRACT FROM AUTHOR]

A de novo topology of virus-like assembly is reported. The design is a trifaceted coiled-coil peptide helix, which self-assembles into ultrasmall, monodisperse, anionic virus-like shells that encapsulate and transfer both RNA and DNA into human cells. Unlike existing artificial systems, these shells share the same physical characteristics of viruses being anionic, nonaggregating, abundant, hollow, and uniform in size, while effectively mediating gene silencing and transgene expression. These are the smallest virus-like structures reported to date, both synthetic and native, with the ability to adapt and transfer small and large nucleic acids. The design thus offers a promising solution for engineering bespoke artificial viruses with desired functions. [ABSTRACT FROM AUTHOR]

A model octapeptide peptide consisting of an alternating sequence of arginine (Arg) and phenylalanine (Phe) residues, namely, [Arg-Phe]4, was prepared, and its self-assembly in solution studied. The simple alternating [Arg-Phe]4 peptide sequence allows for unique insights into the aggregation process and the structure of the self-assembled motifs. Fluorescence and UV-vis assays were used to determine critical aggregation concentrations, corresponding to the formation of oligomeric species and β-sheet rich structures organized into both spheroidal aggregates and highly ordered fibrils. Electron and atomic force microscopy images show globular aggregates and long unbranched fibers with diameters ranging from 4 nm up to 40 nm. Infrared and circular dichroism spectroscopy show the formation of β-sheet structures. X-ray diffraction on oriented stalks show that the peptide fibers have an internal lamellar structure, with an orthorhombic unit cell with parameters a 27.6 Å, b 9.7 Å, and c 9.6 Å. In situ small-angle X-ray scattering (SAXS) shows the presence of low molecular weight oligomers in equilibrium with mature fibers which are likely made up from 5 or 6 intertwined protofilaments. Finally, weak gel solutions are probed under gentle shear, suggesting the ability of these arginine-rich fibers to form networks. [ABSTRACT FROM AUTHOR]

Amyloid fibrils are formed by a modelsurfactant-like peptide (Ala)10-(His)6containinga hexa-histidine tag. Thispeptide undergoes a remarkable two-step self-assembly process withtwo distinct critical aggregation concentrations (cac’s), probedby fluorescence techniques. A micromolar range cac is ascribed tothe formation of prefibrillar structures, whereas a millimolar rangecac is associated with the formation of well-defined but more compactfibrils. We examine the labeling of these model tagged amyloid fibrilsusing Ni-NTA functionalized gold nanoparticles (Nanogold). Successfullabeling is demonstrated via electron microscopy imaging. The specificityof tagging does not disrupt the β-sheet structure of the peptidefibrils. Binding of fibrils and Nanogold is found to influence thecircular dichroism associated with the gold nanoparticle plasmon absorptionband. These results highlight a new approach to the fabrication offunctionalized amyloid fibrils and the creation of peptide/nanoparticlehybrid materials. [ABSTRACT FROM AUTHOR]