RESUMEN
The molecular analysis of biomolecular-membrane interactions is central to understanding most cellular systems but has emerged as a complex technical challenge given the complexities of membrane structure and composition across all living cells. We present a review of the application of surface plasmon resonance and dual polarization interferometry-based biosensors to the study of biomembrane-based systems using both planar mono- or bilayers or liposomes. We first describe the optical principals and instrumentation of surface plasmon resonance, including both linear and extraordinary transmission modes and dual polarization interferometry. We then describe the wide range of model membrane systems that have been developed for deposition on the chips surfaces that include planar, polymer cushioned, tethered bilayers, and liposomes. This is followed by a description of the different chemical immobilization or physisorption techniques. The application of this broad range of engineered membrane surfaces to biomolecular-membrane interactions is then overviewed and how the information obtained using these techniques enhance our molecular understanding of membrane-mediated peptide and protein function. We first discuss experiments where SPR alone has been used to characterize membrane binding and describe how these studies yielded novel insight into the molecular events associated with membrane interactions and how they provided a significant impetus to more recent studies that focus on coincident membrane structure changes during binding of peptides and proteins. We then discuss the emerging limitations of not monitoring the effects on membrane structure and how SPR data can be combined with DPI to provide significant new information on how a membrane responds to the binding of peptides and proteins.
Asunto(s)
Membrana Celular/química , Interferometría/métodos , Membrana Dobles de Lípidos/química , Liposomas/química , Resonancia por Plasmón de Superficie/métodos , Técnicas Biosensibles/métodos , Proteínas de la Membrana/química , Péptidos/químicaRESUMEN
Glycopeptide antibiotics (GPAs) are important antibiotics that are highly challenging to synthesise due to their unique and heavily crosslinked structure. Given this, the synthetic production and diversification of this key compound class remains impractical. Furthermore, the possibility of biosynthetic reengineering of GPAs is not yet feasible since the selectivity of the biosynthetic crosslinking enzymes for altered substrates is largely unknown. We show that combining peptide synthesis with enzymatic cyclisation enables the formation of novel examples of GPAs and provides an indication of the utility of these crucial enzymes. By accessing the biosynthetic process inâ vitro, we identified peptide modifications that are enzymatically tolerated and can also reveal the mechanistic basis for substrate intolerance where present. Using this approach, we next specifically activated modified residues within GPAs for functionalisation at previously inaccessible positions, thereby offering the possibility of late-stage chemical functionalisation after GPA cyclisation is complete.
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Antibacterianos/síntesis química , Glicopéptidos/síntesis química , Antibacterianos/química , Ciclización , Glicopéptidos/químicaRESUMEN
Grb7 is an adapter protein, overexpressed in HER2+ve breast and other cancers, and identified as a therapeutic target. Grb7 promotes both proliferative and migratory cellular pathways through interaction of its SH2 domain with upstream binding partners including HER2, SHC, and FAK. Here we present the evaluation of a series of monocyclic and bicyclic peptide inhibitors that have been developed to specifically and potently target the Grb7 SH2-domain. All peptides tested were found to inhibit signaling in both ERK and AKT pathways in SKBR-3 and MDA-MB-231 cell lines. Proliferation, migration, and invasion assays revealed, however, that the second-generation bicyclic peptides were not more bioactive than the first generation G7-18NATE peptide, despite their higher in vitro affinity for the target. This was found not to be due to steric hindrance by the cell-permeability tag, as ascertained by ITC, but to differences in the ability of the bicyclic peptides to interact with and penetrate cellular membranes, as determined using SPR and mass spectrometry. These studies reveal that just small differences to amino acid composition can greatly impact the effectiveness of peptide inhibitors to their intracellular target and demonstrate that G7-18NATE remains the most effective peptide inhibitor of Grb7 developed to date.
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Antineoplásicos/farmacología , Células Epiteliales/efectos de los fármacos , Proteína Adaptadora GRB7/antagonistas & inhibidores , Regulación Neoplásica de la Expresión Génica , Péptidos Cíclicos/farmacología , Transducción de Señal/efectos de los fármacos , Secuencia de Aminoácidos , Antineoplásicos/síntesis química , Sitios de Unión , Línea Celular , Línea Celular Tumoral , Permeabilidad de la Membrana Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Proteína Adaptadora GRB7/genética , Proteína Adaptadora GRB7/metabolismo , Humanos , Membrana Dobles de Lípidos/química , Membrana Dobles de Lípidos/metabolismo , Péptidos Cíclicos/síntesis química , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Fosfatidilserinas/química , Fosfatidilserinas/metabolismo , Unión Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/genética , Relación Estructura-Actividad , Dominios Homologos src/efectos de los fármacosRESUMEN
Natural products such as the glycopeptide antibiotics (GPAs, including vancomycin and teicoplanin) are of great pharmaceutical importance due to their use against Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus. GPAs are assembled in a complex process based on nonribosomal peptide synthesis and late-stage, multistep cross-linking of the linear heptapeptide performed by cytochrome P450 monooxygenases. These P450 enzymes demonstrate varying degrees of substrate selectivity toward the linear peptide precursor, with limited information available about their tolerance regarding modifications to amino acid residues within the essential antibiotic core of the GPA. In order to test the acceptance of altered residues by the P450-catalyzed cyclization cascade, we have explored the use of ß-amino acids in both variable and highly conserved positions within GPA peptides. Our results indicate that the incorporation of ß-amino acids at the C-terminus of the peptide leads to a dramatic reduction in the efficiency of peptide cyclization by the P450s during GPA biosynthesis, whereas replacement of residue 3 is well tolerated by the same enzymes. These results show that maintaining the C-terminal 3,5-dihydroxyphenylglycine residue is of key importance to maintain the efficiency of this complex and essential enzymatic cross-linking process.
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Aminoácidos/química , Antibacterianos/biosíntesis , Glicopéptidos/biosíntesis , Ciclización , Oxidación-ReducciónRESUMEN
We have studied the effect of penetratin and a truncated analogue on the bilayer structure using dual polarisation interferometry, to simultaneously measure changes in mass per unit area and birefringence (an optical parameter representing bilayer order) with high sensitivity during the binding and dissociation from the membrane. Specifically, we studied penetratin (RQIKIWFQNRRMKWKK), along with a shortened and biotinylated version known as R8K-biotin (RRMKWKKK(Biotin)-NH2). Overall both peptides bound only weakly to the neutral DMPC and POPC bilayers, while much higher binding was observed for the anionic DMPC/DMPG and POPC/POPG. The binding of penetratin to gel-phase DMPC/DMPG was adequately represented by a two-state model, whereas on the fluid-phase POPC/POPG it exhibited a distinctly different binding pattern, best represented by a three-state kinetic model. However, R8K-biotin did not bind well to DMPC/DMPG and showed a more transitory and superficial binding to POPC/POPG. Comparing the modelling results for both peptides binding to POPC/POPG suggests an important role for a securely bound intermediate prior to penetratin insertion and translocation. Overall these results further elucidate the mechanism of penetratin, and provide another example of the significance of the ability of DPI to measure structural changes and the use of kinetic analysis to investigate the stages of peptide-membrane interactions.
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Péptidos de Penetración Celular/farmacología , Membrana Dobles de Lípidos/química , Secuencia de Aminoácidos , Biotinilación , Birrefringencia , Proteínas Portadoras/farmacología , Dimiristoilfosfatidilcolina/química , Geles , Interferometría , Cinética , Liposomas/química , Lípidos de la Membrana/química , Modelos Químicos , Fragmentos de Péptidos/farmacología , Fosfatidilcolinas/química , Fosfatidilgliceroles/química , Unión Proteica , Relación Estructura-ActividadRESUMEN
ß-Peptides have great potential as novel biomaterials and therapeutic agents, due to their unique ability to self-assemble into low dimensional nanostructures, and their resistance to enzymatic degradation in vivo. However, the self-assembly mechanisms of ß-peptides, which possess increased flexibility due to the extra backbone methylene groups present within the constituent ß-amino acids, are not well understood due to inherent difficulties of observing their bottom-up growth pathway experimentally. A computational approach is presented for the bottom-up modelling of the self-assembled lipidated ß3-peptides, from monomers, to oligomers, to supramolecular low-dimensional nanostructures, in all-atom detail. The approach is applied to elucidate the self-assembly mechanisms of recently discovered, distinct structural morphologies of low dimensional nanomaterials, assembled from lipidated ß3-peptide monomers. The resultant structures of the nanobelts and the twisted fibrils are stable throughout subsequent unrestrained all-atom molecular dynamics simulations, and these assemblies display good agreement with the structural features obtained from X-ray fiber diffraction and atomic force microscopy data. This is the first reported, fully-atomistic model of a lipidated ß3-peptide-based nanomaterial, and the computational approach developed here, in combination with experimental fiber diffraction analysis and atomic force microscopy, will be useful in elucidating the atomic scale structure of self-assembled peptide-based and other supramolecular nanomaterials.
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Simulación de Dinámica Molecular , Nanoestructuras , Péptidos , Nanoestructuras/química , Péptidos/química , Lípidos/química , Microscopía de Fuerza AtómicaRESUMEN
BACKGROUND AND PURPOSE: This study investigated the reno-protective effects of a highly selective AT2R agonist peptide, ß-Pro7Ang III in a mouse model of acute kidney injury (AKI). METHODS: C57BL/6 J mice underwent either sham surgery or unilateral kidney ischemia-reperfusion injury (IRI) for 40 min. IRI mice were treated with either ß-Pro7Ang III or perindopril and at 7 days post-surgery the kidneys analysed for histopathology and the development of fibrosis and matrix metalloproteinase (MMP)-2 and -9 activity. The association of the therapeutic effects of ß-Pro7Ang III with macrophage number and phenotype was determined in vivo and in vitro. KEY RESULTS: Decreased kidney tubular injury, interstitial matrix expansion and reduced interstitial immune cell infiltration in IRI mice receiving ß-Pro7Ang III treatment was observed at day 7, compared to IRI mice without treatment. This correlated to reduced collagen accumulation and MMP-2 activity in IRI mice following ß-Pro7Ang III treatment. FACS analysis showed a reduced number and proportion of CD45+CD11b+F4/80+ macrophages in IRI kidneys in response to ß-Pro7Ang III, correlating with a significant increase in M2 macrophage markers and decreased M1 markers at day 3 and 7 post-IR injury, respectively. In vitro analysis of cultured THP-1 cells showed that ß-Pro7Ang III attenuated lipopolysaccharide (LPS)-induced tumour necrosis factor-α (TNF-α) and interleukin (IL)- 6 production but increased IL-10 secretion, compared to LPS alone. CONCLUSION: Administration of ß-Pro7Ang III via mini-pump improved kidney structure and reduced interstitial collagen accumulation, in parallel with an alteration of macrophage phenotype and anti-inflammatory cytokine release, therefore mitigating the downstream progression of ischemic AKI.
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Lesión Renal Aguda , Daño por Reperfusión , Ratones , Animales , Lipopolisacáridos/farmacología , Ratones Endogámicos C57BL , Riñón , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/prevención & control , Colágeno/farmacología , Daño por Reperfusión/genética , ReperfusiónRESUMEN
Determining the porosity of hydrogels is an important component of material characterisation. While scanning electron microscopy (SEM) is a widely used method to study hydrogel nanoarchitecture, it is well-established that SEM sample preparation methods can alter the structure of hydrogels. Herein we describe the impact of sample preparation on the SEM analysis of self-assembling ß-peptide hydrogels. Three methods of hydrogel preparation for SEM were compared, and each method preserved distinctly different nanoarchitecture, specifically, different levels of fibre alignment and porosity. Comparison of conventional SEM preparation and our hybrid method, which comprises high pressure freezing, freeze substitution without fixative and critical point drying, showed a high degree of similarity at the nanometre scale and diverging architecture at the micron scale. This study quantified the impact of chemical fixation versus high pressure freezing on self-assembling ß3-peptide hydrogels, demonstrated the effect of sample preparation on fibre alignment and porosity, and presents a novel hybrid preparation method where chemical fixation can be avoided when conventional SEM is desired.
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Hidrogeles , Péptidos , Hidrogeles/química , Microscopía Electrónica de Rastreo , CongelaciónRESUMEN
Self-assembling lipopeptide hydrogels have been widely developed for the delivery of therapeutics due to their rapid gelation, injectability, and highly controlled physicochemical properties. Lipopeptides are also known for their membrane-associating and cell penetrating properties, which may impact on their application in cell-encapsulation. Self-assembling lipidated-ß3-peptide materials developed in our laboratory have previously been used in cell culture as 2D substrates, thus as a continuation of this work we aimed to encapsulate cells in 3D by forming a hydrogel. We therefore assessed the self-assembling lipidated-ß3-peptides for cell-penetrating properties in mesenchymal stems cells (MSC) using fluorescence microscopy and membrane association with surface plasmon resonance spectroscopy (SPR). The results demonstrated that lipidated ß3-peptides penetrate the MSC plasma membrane and localise to the mitochondrial network. While self-assembling lipopeptide hydrogels have shown tremendous potential for delivery of therapeutics, further optimisation may be required to minimise the membrane uptake of the lipidated-ß3-peptides for cell encapsulation applications.
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Técnicas de Cultivo de Célula , Lipopéptidos , Transporte Biológico , Membrana Celular , HidrogelesRESUMEN
Small tripeptides composed entirely of ß3-amino acids have been shown to self-assemble into fibres following acylation of the N-terminus. Given the use of Fmoc as a strategy to initiate self-assembly in α-peptides, we hypothesized that the acyl cap can be replaced by an Fmoc without perturbation to the self-assembly and enable simpler synthetic protocols. We therefore replaced the N-acyl cap for an Fmoc group and herein we show that these Fmoc-protected ß3-peptides produce regular spherical particles, rather than fibrous structures, that are stable and capable of encapsulating cargo. We then demonstrated that these particles were able to deliver cargo to cells without any obvious signs of cytotoxicity. This is the first description of such regular nanoparticles derived from Fmoc-protected ß3-peptides.
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Stimulation of the angiotensin II type 2 receptor (AT2R) evokes protective effects in various cardiovascular diseases. Thus, this study aimed to investigate the effects of AT2R stimulation, with or without AT1R blockade, in a model of hypertension with concomitant type 1 diabetes mellitus (T1DM). Spontaneously hypertensive rats (SHRs) were given either citrate or a single dose of streptozotocin (STZ; 55 mg/kg, i.p.) to induce diabetes. After 4 weeks of diabetes, animals were administered either a vehicle (saline), AT2R agonist, ß-Pro7Ang III (0.1 mg/kg/day via osmotic mini-pump), AT1R blocker, candesartan (2 mg/kg/day via drinking water), or a combination of both for a further 8 weeks. ß-Pro7Ang III treatment had no effect on blood pressure, but attenuated the significant increase in cardiac interstitial collagen and protein expression of fibrotic and inflammatory markers, and superoxide levels that was evident in diabetic SHRs. These effects were not observed with candesartan, despite its blood pressure lowering effects. Although ß-Pro7Ang III had no effect on aortic fibrosis, it significantly attenuated MCP-1 protein expression and superoxide levels when compared to both the non-diabetic and diabetic SHRs, to a similar extent as candesartan. In both the heart and vasculature, the effects of ß-Pro7Ang III in combination with candesartan were similar to those of ß-Pro7Ang III alone, and superior to candesartan alone. It was concluded that in hypertension with concomitant diabetes, AT2R stimulation with a novel ligand alone, or in combination with AT1R blockade, improved the cardiac and vascular structural changes that were strongly associated with inflammation and oxidative stress, independent of blood pressure regulation.
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Diabetes Mellitus , Hipertensión , Animales , Ratas , Bencimidazoles/farmacología , Bencimidazoles/uso terapéutico , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Ratas Endogámicas SHR , Receptor de Angiotensina Tipo 1/metabolismo , Superóxidos , CardiotónicosRESUMEN
Peptide self-assembly has been exploited to generate a multitude of biomaterials that exhibit biocompatibility due to their similarity to naturally occurring proteins. Previously, we have shown that ß-tripeptides self-assemble despite containing sterically bulky, functional sidechains. Herein, we describe the synthesis of a novel ß-amino acid to allow for the synthesis of a trifunctional ß-tripeptide that remarkably maintains self-assembly and acts as a bioactive neuronal scaffold. These scaffolds show promise for studies involving neuronal cell growth and development.
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Neuronas/química , Oligopéptidos/química , Andamios del Tejido/química , Proliferación CelularRESUMEN
The novel RNA virus, severe acute respiratory syndrome coronavirus II (SARS-CoV-2), is currently the leading cause of mortality in 2020, having led to over 1.6 million deaths and infecting over 75 million people worldwide by December 2020. While vaccination has started and several clinical trials for a number of vaccines are currently underway, there is a pressing need for a cure for those already infected with the virus. Of particular interest in the design of anti-SARS-CoV-2 therapeutics is the human protein angiotensin converting enzyme II (ACE2) to which this virus adheres before entry into the host cell. The SARS-CoV-2 virion binds to cell-surface bound ACE2 via interactions of the spike protein (s-protein) on the viral surface with ACE2. In this paper, we use all-atom molecular dynamics simulations and binding enthalpy calculations to determine the effect that a bound ACE2 active site inhibitor (MLN-4760) would have on the binding affinity of SARS-CoV-2 s-protein with ACE2. Our analysis indicates that the binding enthalpy could be reduced for s-protein adherence to the active site inhibitor-bound ACE2 protein by as much as 1.48-fold as an upper limit. This weakening of binding strength was observed to be due to the destabilization of the interactions between ACE2 residues Glu-35, Glu-37, Tyr-83, Lys-353, and Arg-393 and the SARS-CoV-2 s-protein receptor binding domain (RBD). The conformational changes were shown to lead to weakening of ACE2 interactions with SARS-CoV-2 s-protein, therefore reducing s-protein binding strength. Further, we observed increased conformational lability of the N-terminal helix and a conformational shift of a significant portion of the ACE2 motifs involved in s-protein binding, which may affect the kinetics of the s-protein binding when the small molecule inhibitor is bound to the ACE2 active site. These observations suggest potential new ways for interfering with the SARS-CoV-2 adhesion by modulating ACE2 conformation through distal active site inhibitor binding.
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Enzima Convertidora de Angiotensina 2/metabolismo , Inhibidores de Proteasas/metabolismo , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Enzima Convertidora de Angiotensina 2/antagonistas & inhibidores , Sitios de Unión , COVID-19/patología , COVID-19/virología , Dominio Catalítico , Diseño de Fármacos , Humanos , Enlace de Hidrógeno , Simulación de Dinámica Molecular , Inhibidores de Proteasas/química , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Estructura Terciaria de Proteína , SARS-CoV-2/aislamiento & purificación , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , TermodinámicaRESUMEN
Parkinson's disease (PD) is a progressive neurological disorder, in which dopaminergic midbrain neurons degenerate, leading to dopamine depletion that is associated with neuronal death. In this Review, we initially describe the pathogenesis of PD and established therapies that unfortunately only delay progression of the disease. With a rapidly escalating incidence in PD, there is an urgent need to develop new therapies that not only halt progression but even reverse degeneration. Biomaterials are playing critical roles in these new therapies which include controlled and site-specific delivery of neurotrophins, increased engraftment of implanted neural stem cells, and redirection of endogenous stem cell populations away from their niche to encourage reparative mechanisms. This Review will therefore cover important design features of biomaterials used in regenerative medicine and tissue engineering strategies targeted at PD.
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Células-Madre Neurales , Enfermedad de Parkinson , Materiales Biocompatibles , Dopamina , Neuronas Dopaminérgicas , Humanos , Enfermedad de Parkinson/terapiaRESUMEN
The increasing resistance of pathogenic microbes to antimicrobials and the shortage of antibiotic drug discovery programs threaten the clinical use of antibiotics. This threat calls for the development of new methods for control of drug-resistant microbial pathogens. We have designed, synthesised and characterised an antimicrobial material formed via the self-assembly of a population of two distinct ß-peptide monomers, a lipidated tri-ß-peptide (ß3-peptide) and a novel ß3-peptide conjugated to a glycopeptide antibiotic, vancomycin. The combination of these two building blocks resulted in fibrous assemblies with distinctive structures determined by atomic force microscopy and electron microscopy. These fibres inhibited the growth of methicillin resistant Staphylococcus aureus (MRSA) and associated directly with the bacteria, acting as a peptide nanonet with fibre nucleation sites on the bacteria observed by electron microscopy and confocal microscopy. Our results provide insights into the design of peptide based supramolecular assemblies with antibacterial activity and establish an innovative strategy to develop self-assembled antimicrobial materials for future biomedical application.
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A synthetic strategy for conjugating small molecules and peptide-based therapeutics, via a cleavable ester bond, to a lipidated ß3-tripeptide is presented. The drug-loaded ß3-peptide was successfully co-assembled with a functionally inert lipidated ß3-tripeptide to form a hydrogel. Quantitative release of lactose from the hydrogel, by the action of serum esterases, is demonstrated over 28 days. The esterase-mediated sustained release of the bioactive brain-derived neurotrophic factor (BDNF) peptide mimics from the hydrogel resulted in increased neuronal survival and normal neuronal function of peripheral neurons. These studies define a versatile strategy for the facile synthesis and co-assembly of self-assembling ß3-peptide-based hydrogels with the ability to control drug release using endogenous esterases with potential in vivo applications for sustained localized drug delivery.
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Esterasas/metabolismo , Hidrogeles/farmacología , Neuronas/efectos de los fármacos , Péptidos/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Liberación de Fármacos , Esterasas/sangre , Femenino , Hidrogeles/química , Hidrogeles/metabolismo , Ensayo de Materiales , Estructura Molecular , Neuronas/metabolismo , Péptidos/química , Péptidos/metabolismo , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
A new method for in-gel sample processing and tryptic digestion of proteins is described. Sample preparation, rehydration, in situ digestion and peptide extraction from gel slices are dramatically accelerated by treating the gel slice with surface acoustic waves (SAWs). Only 30 minutes total workflow time is required for this new method to produce base peak chromatograms (BPCs) of similar coverage and intensity to those observed for traditional processing and overnight digestion. Simple set up, good reproducibility, excellent peptide recoveries, rapid turnover of samples and high confidence protein identifications put this technology at the fore-front of the next generation of proteomics sample processing tools.
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Acústica , Métodos Analíticos de la Preparación de la Muestra/instrumentación , Proteínas/metabolismo , Animales , Bovinos , Geles , Humanos , Técnicas Analíticas Microfluídicas , Modelos Moleculares , Conformación Proteica , Proteínas/química , Propiedades de Superficie , Factores de TiempoRESUMEN
ß3-peptides consisting exclusively of ß3-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-ß3-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 ß3-tripeptide foldamers can be tuned via sequential lipidation of N-acetyl ß3-tripeptides which control the lateral interactions between peptide fibrils and provide defined structures with a greater homogeneous population.
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A new modality for chemical synthesis on a drop scale which employs a piezoelectric chip as the reactor and surface acoustic waves (SAWs) as the source of energy (and consequent heating) is described.
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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 ß-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 ß-peptide foldamers with a specific focus on N-acetyl-ß3-peptides and their applications as bio- and nanomaterials.