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1.
Langmuir ; 38(11): 3434-3445, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35274959

RESUMO

Peptide-based hydrogels have attracted much attention due to their extraordinary applications in biomedicine and offer an excellent mimic for the 3D microenvironment of the extracellular matrix. These hydrated matrices comprise fibrous networks held together by a delicate balance of intermolecular forces. Here, we investigate the hydrogelation behavior of a designed decapeptide containing a tetraleucine self-assembling backbone and fibronectin-related tripeptides near both ends of the strand. We have observed that this synthetic peptide can produce hydrogel matrices entrapping >99% wt/vol % water. Ultrastructural analyses combining atomic force microscopy, small-angle neutron scattering, and X-ray diffraction revealed that amyloid-like fibrils form cross-linked networks endowed with remarkable thermal stability, the structure of which is not disrupted up to temperatures >80 °C. We also examined the interaction of peptide hydrogels with either NIH3T3 mouse fibroblasts or HeLa cells and discovered that the matrices sustain cell viability and induce morphogenesis into grape-like cell spheroids. The results presented here show that this decapeptide is a remarkable building block to prepare highly stable scaffolds simultaneously endowed with high water retention capacity and the ability to instruct cell growth into tumor-like spheroids even in noncarcinoma lineages.


Assuntos
Hidrogéis , Nanoestruturas , Amiloide , Animais , Células HeLa , Humanos , Hidrogéis/química , Camundongos , Morfogênese , Células NIH 3T3 , Nanoestruturas/toxicidade , Peptídeos/química , Água
2.
ACS Appl Bio Mater ; 5(3): 905-944, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35195008

RESUMO

This review discusses peptide epitopes used as antigens in the development of vaccines in clinical trials as well as future vaccine candidates. It covers peptides used in potential immunotherapies for infectious diseases including SARS-CoV-2, influenza, hepatitis B and C, HIV, malaria, and others. In addition, peptides for cancer vaccines that target examples of overexpressed proteins are summarized, including human epidermal growth factor receptor 2 (HER-2), mucin 1 (MUC1), folate receptor, and others. The uses of peptides to target cancers caused by infective agents, for example, cervical cancer caused by human papilloma virus (HPV), are also discussed. This review also provides an overview of model peptide epitopes used to stimulate non-specific immune responses, and of self-adjuvanting peptides, as well as the influence of other adjuvants on peptide formulations. As highlighted in this review, several peptide immunotherapies are in advanced clinical trials as vaccines, and there is great potential for future therapies due the specificity of the response that can be achieved using peptide epitopes.


Assuntos
Vacinas de Subunidades/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Antígenos/imunologia , Vacinas Anticâncer/administração & dosagem , Controle de Doenças Transmissíveis , Humanos , Neoplasias/terapia , Peptídeos/imunologia
3.
Soft Matter ; 18(4): 711-721, 2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35014650

RESUMO

Lamellar structures are formed in a variety of soft materials including lipids, surfactants, block polymers, clays, colloids, semicrystalline polymers and others. Lamellar phases are characterized by scattering patterns containing pseudo-Bragg peaks from the layer ordering. However, fluctuations of the lamellae give rise to diffuse scattering in addition. This diffuse scattering can provide valuable information on the elastic properties of lamellae which control their fluctuations. A number of models to account for this are described in this Tutorial Review, along with examples from the literature. In addition, diffuse scattering from in-plane fluctuations or structures such as perforations or patterned nanoparticles is considered. This type of diffuse scattering can give unique information on the nature of, and positional (and bond orientational) ordering within, correlated structures within the lamellar plane. Anisotropic diffuse scattering features from thermotropic smectic phases is also briefly discussed.

4.
Chem Commun (Camb) ; 57(67): 8360-8363, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34338257

RESUMO

The self-assembly in aqueous solution of benzene-1,3,5-tricarboxamide (BTA) bearing one alkyl chain and two PEG (polyethylene glycol) chains or two alkyl chains and one PEG chain yields completely distinct nanostructures. Two series of derivatives were synthesized and extensively characterized and electron microscopy and small-angle X-ray scattering (SAXS) reveal micelle structures for derivatives with one alkyl and two PEG chains, but nanotapes and nanoribbons for the series with two alkyl and one PEG chain.

5.
Langmuir ; 37(30): 9170-9178, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34292730

RESUMO

The peptide angiotensin-converting enzyme inhibitors captopril and lisinopril are unexpectedly shown to exhibit critical aggregation concentration (CAC) behavior through measurements of surface tension, electrical conductivity, and dye probe fluorescence. These three measurements provide similar values for the CAC, and there is also evidence from circular dichroism spectroscopy for a possible conformational change in the peptides at the same concentration. Cryogenic transmission electron microscopy indicates the formation of micelle-like aggregates above the CAC, which can thus be considered a critical micelle concentration, and the formation of aggregates with a hydrodynamic radius of ∼6-7 nm is also evidenced by dynamic light scattering. We also used synchrotron radiation X-ray diffraction to determine the single-crystal structure of captopril and lisinopril. Our results improve the accuracy of previous data reported in the literature, obtained using conventional X-ray sources. We also studied the structure of aqueous solutions containing captopril or lisinopril at high concentrations. The aggregation may be driven by intermolecular interactions between the proline moiety of captopril molecules or between the phenylalanine moiety of lisinopril molecules.


Assuntos
Captopril , Lisinopril , Inibidores da Enzima Conversora de Angiotensina
6.
Bioconjug Chem ; 32(8): 1472-1490, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34228433

RESUMO

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.


Assuntos
Lipopeptídeos/química , Vacinas/química , Animais , Humanos , Lipopeptídeos/imunologia , Vacinas/imunologia
8.
Biomacromolecules ; 22(5): 1835-1855, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33843196

RESUMO

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 ß-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.


Assuntos
Nanoestruturas , Peptídeos , Catálise , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta
9.
Soft Matter ; 17(11): 3096-3104, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33598669

RESUMO

A designed surfactant-like peptide is shown, using a combination of cryogenic-transmission electron microscopy and small-angle X-ray scattering, to have remarkable pH-dependent self-assembly properties. Peptide Arg3-Leu12 (R3L12) forms a network of peptide nanotubes at pH 9 and below. These are associated with α-helical conformation in a "cross-α" nanotube structure, in which peptide dimers lie perpendicular to the nanotube axis, with arginine coated inner and outer nanotube walls. In contrast, this peptide forms decorated vesicular aggregates at higher pH values, close to the pKa of the arginine residues. These structures are associated with a loss of α-helical order as detected through X-ray scattering, circular dichroism and FTIR spectroscopy, the latter technique also revealing a loss of ordering of leucine side chains. This suggests a proposed model for the decorated or patchy vesicular structures that comprises disordered peptide as the matrix of the membrane, with small domains of ordered peptide dimers forming the minority domains. We ascribe this to a lipid-raft like phase separation process, due to conformational disordering of the leucine hydrophobic chains. The observation of the self-assembly of a simple surfactant-like peptide into these types of nanostructure is remarkable, and peptide R3L12 shows unique pH-dependent morphological and conformational behaviour, with the potential for a range of future applications.


Assuntos
Nanoestruturas , Tensoativos , Dicroísmo Circular , Concentração de Íons de Hidrogênio , Peptídeos , Conformação Proteica em alfa-Hélice
10.
J Synchrotron Radiat ; 28(Pt 1): 318-321, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33399583

RESUMO

The design of a multipurpose sample cell holder for the high-throughput (HT) beamline B21 is presented. The device is compatible with the robot bioSAXS sample changer currently installed on BM29, ESRF, and P12 Petra IV synchrotrons. This work presents an approach that uses 3D-printing to make hardware alterations which can expand the versatility of HT beamlines at low cost.

11.
Soft Matter ; 16(44): 9998-10000, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33150351
12.
Langmuir ; 36(48): 14793-14801, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33210929

RESUMO

The aggregation of two short peptides, [RF] and [RF]4 (where R = arginine and F = phenylalanine), at dipalmitoylphosphatidylcholine (DPPC) model membranes was investigated at the air-water interface using the Langmuir technique and vesicles in aqueous solutions. The molar ratio of the peptide and lipid components was varied to provide insights into the peptide-membrane interactions, which might be related to their cytotoxicity. Both peptides exhibited affinity to the DPPC membrane interface and rapidly adopted ß-sheet-rich structures upon adsorption onto the surface of the zwitterionic membrane. Results from adsorption isotherm and small-angle X-ray scattering experiments showed changes in the structural and thermodynamic parameters of the membrane with increasing peptide concentration. Using atomic force microscopy, we showed the appearance of pores through the bilayer membranes and peptide aggregation at different interfaces, suggesting that the hydrophobic residues might have an effect on both pore size and layer structure, facilitating the membrane disruption and leading to different cytotoxicity effects.


Assuntos
1,2-Dipalmitoilfosfatidilcolina , Peptídeos , Adsorção , Amiloide , Bicamadas Lipídicas , Peptídeos/toxicidade , Termodinâmica
13.
Chem Commun (Camb) ; 56(80): 11977-11980, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33033814

RESUMO

The designed arginine-rich surfactant-like peptide R3L12 (arginine3-leucine12) is shown to form a remarkable diversity of self-assembled nanostructures in aqueous solution, depending on pH, including nanotubes, mesh-like tubular networks in three-dimensions and square planar arrays in two-dimensions. These structures are built from α-helical antiparallel coiled-coil peptide dimers arranged perpendicular to the nanotube axis, in a "cross-α" nanotube structure. The aggregation behavior is rationalized based on the effects of dimensionality, and the balance of hydrophobic and electrostatic interactions. The nanotube and nanomesh structures display arginine at high density on their surfaces, which may be valuable for future applications.


Assuntos
Leucina/química , Nanoestruturas/química , Nanotubos de Peptídeos/química , Tensoativos/química , Sequência de Aminoácidos , Arginina/química , Modelos Moleculares , Conformação Proteica em alfa-Hélice , Multimerização Proteica , Água
14.
Langmuir ; 36(43): 12942-12953, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33078952

RESUMO

A dipeptide-based synthetic amphiphile bearing a myristyl chain has been found to form hydrogels in the pH range 6.9-8.5 and organogels in various organic solvents including petroleum ether, diesel, kerosene, and petrol. These organogels and hydrogels have been thoroughly studied and characterized by different techniques including high-resolution transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and rheology. It has been found that the xerogel obtained from the peptide gelator can trap various toxic organic dyes from wastewater efficiently. Moreover, the hydrogel has been used to remove toxic heavy metal ions Pb2+ and Cd2+ from wastewater. Dye adsorption kinetics has been studied, and it has been fitted by using the Freundlich isotherm equation. Interestingly, the gelator amphiphilic peptide gels fuel oil, kerosene, diesel, and petrol in a biphasic mixture of salt water and oil within a few seconds. This indicates that these gels not only may find application in oil spill recovery but also can be used to remove toxic organic dyes and hazardous toxic metal ions from wastewater. Moreover, the gelator can be recycled several times without significant loss of activity, suggesting the sustainability of this new gelator. This holds future promise for environmental remediation by using peptide-based gelators.

15.
Soft Matter ; 16(44): 10106-10114, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-32716462

RESUMO

A histidine attached naphthalenediimide (NDI)-containing amphiphilic molecule (NDIP) self-assembles into nanotubes in aqueous solution at pH 6.6 as revealed by high-resolution transmission electron microscopy studies. This histidine-appended NDI forms a two-component hydrogel in the presence of tartaric acid at a molar ratio of 1 : 2. A morphological transformation was observed from a nanotube structure in the non-gel aggregated state of histidine appended NDI to interconnected cross-linked nanofibers of the two-component hydrogel in the presence of tartaric acid. Interestingly, the gel exhibits an unusual behavior upon aging compared to the fresh gel. It is found that the thermal stability and gel stiffness increase very significantly upon aging. Another important feature noted is that the very weak fluorescence of the fresh gel is transformed into bright greenish fluorescence upon aging. These results suggest that intermolecular interactions among the gelator molecules and tartaric acid in the gel phase slowly increase with time to form a mechanically very stiff and thermally robust gel.

16.
Chem Soc Rev ; 49(15): 5473-5509, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32632432

RESUMO

Amyloid diseases are global epidemics with profound health, social and economic implications and yet remain without a cure. This dire situation calls for research into the origin and pathological manifestations of amyloidosis to stimulate continued development of new therapeutics. In basic science and engineering, the cross-ß architecture has been a constant thread underlying the structural characteristics of pathological and functional amyloids, and realizing that amyloid structures can be both pathological and functional in nature has fuelled innovations in artificial amyloids, whose use today ranges from water purification to 3D printing. At the conclusion of a half century since Eanes and Glenner's seminal study of amyloids in humans, this review commemorates the occasion by documenting the major milestones in amyloid research to date, from the perspectives of structural biology, biophysics, medicine, microbiology, engineering and nanotechnology. We also discuss new challenges and opportunities to drive this interdisciplinary field moving forward.


Assuntos
Doença de Alzheimer/metabolismo , Amiloide/química , Amiloide/metabolismo , Amiloidose , Cátions Bivalentes/química , Reagentes para Ligações Cruzadas/química , Humanos , Modelos Moleculares , Conformação Molecular , Impressão Tridimensional , Dobramento de Proteína , Processamento de Proteína Pós-Traducional
17.
Front Chem ; 8: 416, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528930

RESUMO

Poly(N-substituted glycine) "peptoids" are an interesting class of peptidomimics that can resist proteolysis and mimic naturally found antimicrobial peptides (AMPs), which exhibit wide spectrum activity against bacteria. This work investigates the possibility of modifying peptoid AMP mimics (AMPMs) with aliphatic lipid "tails" to generate "lipopeptoids" that can assemble into micellar nanostructures, and evaluates their antimicrobial activities. Two families of AMPMs with different distributions of hydrophobic and cationic residues were employed-one with a uniform repeating amphiphilicity, the other with a surfactant-like head-to-tail amphiphilicity. To further evaluate the interplay between self-assembly and activity, the lipopeptoids were variously modified at the AMPM chain ends with a diethylene glycol (EG2) and/or a cationic group (Nlys-Nlys dipeptoid) to adjust amphiphilicity and chain flexibility. Self-assembly was investigated by critical aggregation concentration (CAC) fluorescence assays and dynamic light scattering (DLS). The structure of a key species was also verified by small-angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-EM). To screen for antibacterial properties, we measured the minimum inhibitory concentrations (MIC) against S. aureus, E. coli, and P. aeruginosa. We found that certain combinations of lipid tail and AMPM sequences exhibit increased antibacterial activity (i.e., decreased MICs). Perhaps counter-intuitively, we were particularly interested in increased MICs in combination with low CACs. Concealing antimicrobial interactions due to packing of AMPMs in nano-assemblies could pave the way to AMPMs that may be "inert" even if unintentionally released and prevent microbes from gaining resistance to the lipopeptoids. Overall, incorporation of EG2 significantly improved lipopeptoids packing while the hydrophobic tail length was found to have a major influence over the MIC. One particular sequence, which we named C15-EG2-(kss)4, exhibited a very low CAC of 34 µM (0.0075 wt.%) and a significantly increased MIC above values for the unmodified AMPM. With the sequence design trends uncovered from this study, future work will focus on discovering more species such as C15-EG2-(kss)4 and on investigating release mechanisms and the potency of the released lipopeptoids.

18.
Soft Matter ; 16(19): 4615-4624, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32368775

RESUMO

The self-assembly of model [P]RWG lipopeptides (P: l-proline, R: l-arginine, W: l-tryptophan, G: l-glycine), containing one or two aliphatic octadecyl (C18) chains in water and cyclohexanone/water solutions was examined. The self-assembly of mixtures of these RWG and PRWG lipopeptides was also investigated. These materials presented a similar critical aggregation concentration of ∼4.0 × 10-4 wt% and were characterized by unordered secondary structures with some ß-sheet content. TEM and cryo-TEM revealed the presence of mainly nanotape structures with micelles observed for systems rich in PRWG(C18H37). Analysis of detailed SAXS form factor measurements revealed the presence of bilayers 3-4 nm thick while the PRWG(C18H37) micelles have a core radius of approximately 3 nm, and a shell thickness of 2 nm. For the cyclohexanone/water systems polymorphs containing cluster aggregates (with radius of 0.25 nm to 0.50 nm) and some elongated structures (with radius of 5.7 nm to 26.1 nm) were seen. Longer structures were formed with the increase of the proline-containing lipopeptide content. The catalytic activity of these peptides was assessed using a model nitro-aldol reaction. The concentration of water in the reaction system influenced the conversion, higher content promoted better efficiency for the water systems, but the opposite was observed for the cyclohexanone/water samples.


Assuntos
Lipopeptídeos/química , Prolina/química , Catálise , Dicroísmo Circular , Cicloexanonas/química , Micelas , Microscopia Eletrônica de Transmissão , Estrutura Secundária de Proteína , Espalhamento a Baixo Ângulo , Soluções , Água/química , Difração de Raios X
19.
Dalton Trans ; 49(45): 16226-16237, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-32369068

RESUMO

Morphological, spectroscopic and scattering studies of the self-assembly and aggregation process of hybrids containing gold nanoparticles (AuNPs) and the amyloid peptides [RF]4 and P[RF]4 (where R = arginine; F = phenylalanine; P = proline) in aqueous solution were performed. Two methodologies were tested for the AuNP nucleation, using sodium borohydride (NaBH4) or epigallocatechin gallate (EGCG) as a reducing agent. This led to remarkable distinct modes of assembly, AuNP decorated fibrils with NaBH4 reduction or isolated AuNPs with EGCG reduction. For both methodologies, the presence of spherical AuNPs was observed by plasmonic resonance bands in absorption spectra at ∼520 nm. Zeta potential measurements confirmed stable systems, with a similar aggregation state. Circular dichroism spectra revealed an antiparallel ß-sheet conformation of the peptides. The transmission electron microscopy (TEM) images showed the coexistence of nanometer fibers and globular nanoparticles with 20 nm size. The small-angle X-ray scattering (SAXS) results show that the NaBH4 systems presented large cylindrical structures, while with increasing P[RF]4 content, a decrease in radius was observed. However, the EGCG-AuNPs were characterized by spherical particles, with a radius of 10-20 nm. Also, the colorimetric efficiency of the hybrids in the capture of Cu2+ ions in solution was monitored. Raman spectroscopy data confirmed the conformation/structure of self-assembled samples. Moreover, there are indications for a surface-enhanced Raman spectroscopy (SERS) effect for Cu2+ sites. The set of results indicates that these systems could act as a promising sensitive metal concentration probes.


Assuntos
Colorimetria/métodos , Cobre/análise , Cobre/química , Ouro/química , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas Metálicas/química
20.
ACS Macro Lett ; 9(4): 494-499, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32337093

RESUMO

Peptoids are biofunctional N-substituted glycine peptidomimics. Their self-assembly is of fundamental interest because they demonstrate alternatives to conventional peptide structures based on backbone chirality and beta-sheet hydrogen bonding. The search for self-assembling, water-soluble "minimal" sequences, be they peptide or peptidomimic, is a further challenge. Such sequences are highly desired for their compatibility with biomacromolecules and convenient synthesis for broader application. We report the self-assembly of a set of trimeric, water-soluble α-peptoids that exhibit a relatively low critical aggregation concentration (CAC ∼ 0.3 wt %). Cryo-EM and angle-resolved DLS show different sequence-dependent morphologies, namely uniform ca. 6 nm wide nanofibers, sheets, and clusters of globular assemblies. Absorbance and fluorescence spectroscopies indicate unique phenyl environments for π-interactions in the highly ordered nanofibers. Assembly of our peptoids takes place when the sequences are fully ionized, representing a departure from superficially similar amyloid-type hydrogen-bonded peptide nanostructures and expanding the horizons of assembly for sequence-specific bio- and biomimetic macromolecules.

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