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1.
Chem Commun (Camb) ; 55(58): 8434-8437, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31259350

RESUMO

Phosphatidylcholine is the main component of liposomes and other phospholipid-based nanocarriers in drug delivery. However, the functions and applications of these nanocarriers are extremely limited by conventional phospholipids. Here we report novel disulfide phosphatidylcholines (SS-PCs) and SS-PC based liposomes (SS-LPs) used as alternatives to traditional phospholipids and liposomes.


Assuntos
Dissulfetos/química , Portadores de Fármacos/química , Lipossomos/química , Fosfatidilcolinas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Dissulfetos/síntese química , Dissulfetos/metabolismo , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Humanos , Lipossomos/síntese química , Lipossomos/metabolismo , Camundongos , Oxirredução , Fosfatidilcolinas/síntese química , Fosfatidilcolinas/metabolismo
2.
Chem Commun (Camb) ; 55(65): 9653-9656, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31342021

RESUMO

The fast and accurate real-time monitoring of hydrogen peroxide (H2O2) secreted from living cells plays a critical role in clinical diagnosis and management. Herein, we report low-cost and self-supported MoS2 nanosheet arrays for non-enzymatic eletrochemical H2O2 detection. Under the optimal test conditions, such MoS2 electrodes exhibit extremely promising electrocatalytic performance with a low detection limit of 1.0 µM (S/N = 3) and an excellent sensitivity of 5.3 mA mM-1 cm-2. Furthermore, the detection of the trace amount of H2O2 secreted from live A549 cancer cells was successfully performed with this biosensor.


Assuntos
Dissulfetos/química , Peróxido de Hidrogênio/análise , Molibdênio/química , Nanoestruturas/química , Células A549 , Técnicas Biossensoriais/métodos , Carbono/química , Dissulfetos/síntese química , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção
3.
J Agric Food Chem ; 67(31): 8559-8572, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31298518

RESUMO

Avenin-like b protein is rich in cysteine residues, providing the possibility to form intermolecular disulfide bonds and then participate in glutenin polymerization. Site-directed mutagenesis was adopted to produce mutant avenin-like b gene encoding mutant avenin-like b protein, in which one tyrosine codon at the C-terminal is substituted by a cysteine codon. Compared with the control lines, both transgenic lines with wild-type and mutant avenin-like b genes demonstrated superior dough properties. While compared within the transgenic lines, the mutant lines showed relative weaker dough strength and decreased sodium-dodecyl-sulfate sedimentation volumes (from 69.7 mL in line WT alb-1 to 41.0 mL in line Mut alb-4). These inferior dough properties were accompanied by the lower contents of large-sized glutenin polymers, the decreased particle diameters of glutenin macropolymer (GMP), due to the lower content of intermolecular ß-sheets (from 39.48% for line WT alb-2 to 30.21% for line Mut alb-3) and the varied contents of disulfide bonds (from 137.37 µmol/g for line WT alb-1 to 105.49 µmol/g for line Mut alb-4) in wheat dough. The extra cysteine might alter the original disulfide bond structure, allowing cysteine residue usually involved in an intermolecular disulfide bond to become available for an intrachain disulfide bond. Avenin-like b proteins were detected in glutenin macropolymers, providing further evidence for this protein to participate in the polymerization of glutenin. This is the first time to investigate the effect of a specific cysteine residue in the avenin-like b protein on flour quality.


Assuntos
Cisteína/genética , Farinha/análise , Plantas Geneticamente Modificadas/genética , Prolaminas/genética , Triticum/genética , Pão/análise , Cisteína/metabolismo , Dissulfetos/química , Manipulação de Alimentos , Mutagênese Sítio-Dirigida , Plantas Geneticamente Modificadas/química , Plantas Geneticamente Modificadas/metabolismo , Prolaminas/metabolismo , Triticum/química , Triticum/metabolismo
4.
Chem Soc Rev ; 48(16): 4361-4374, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31294429

RESUMO

Antibody-Drug Conjugates (ADCs) are now established as a major class of therapeutics for the clinical treatment of cancer. The properties of the linker between the antibody and the payload are proven to be critical to the success of an ADC. Although ADC linkers can be 'non-cleavable', the vast majority of ADCs in clinical development have specific release mechanisms to allow controlled linker cleavage at the target site and are thus termed 'cleavable'. In recent years, the development of new methods of drug release from ADCs has continued in parallel to the deepening understanding of the biological processes underlying the mechanisms of action of pre-existing technologies. This review summarises the advances in the field of cleavable linker technologies for ADCs.


Assuntos
Anticorpos Monoclonais/química , Imunoconjugados/química , Ácidos/química , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Catepsina B/metabolismo , Dissulfetos/química , Estabilidade de Medicamentos , Humanos , Imunoconjugados/sangue , Imunoconjugados/metabolismo
5.
J Nanobiotechnology ; 17(1): 78, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269964

RESUMO

BACKGROUND: The construction of a multifunctional drug delivery system with a variety of advantageous features, including targeted delivery, controlled release and combined therapy, is highly attractive but remains a challenge. RESULTS: In this study, we developed a MoS2-based hyaluronic acid (HA)-functionalized nanoplatform capable of achieving targeted delivery of camptothecin (CPT) and dual-stimuli-responsive drug release. HA was connected to MoS2 via a disulfide linkage, forming a sheddable HA shell on the surface of MoS2. This unique design not only effectively prevented the encapsulated CPT from randomly leaking during blood circulation but also significantly accelerated the drug release in response to tumor-associated glutathione (GSH). Moreover, the MoS2-based generated heat upon near-infrared (NIR) irradiation could further increase the drug release rate as well as induce photothermal ablation of cancer cells. The results of in vitro and in vivo experiments revealed that MoS2-SS-HA-CPT effectively suppressed cell proliferation and inhibited tumor growth in lung cancer cell-bearing mice under NIR irradiation via synergetic chemo-photothermal therapy. CONCLUSIONS: The as-prepared MoS2-SS-HA-CPT with high targeting ability, dual-stimuli-responsive drug release, and synergistic chemo-photothermal therapy may provide a new strategy for cancer therapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/administração & dosagem , Dissulfetos/química , Portadores de Fármacos/química , Molibdênio/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Liberação Controlada de Fármacos , Feminino , Corantes Fluorescentes/química , Humanos , Ácido Hialurônico/química , Hipertermia Induzida , Raios Infravermelhos , Camundongos Nus , Transplante de Neoplasias , Oxirredução , Fotoquimioterapia/métodos
6.
Talanta ; 202: 342-348, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31171193

RESUMO

A molecular beacons (MBs) loaded on molybdenum disulfide (MoS2) nanosheets as fluorescence probes for sensitive and versatile detection of microRNAs (miRNAs) through hybridization chain reaction (HCR) has been designed. MoS2 was used as a adsorbent to capture the MBs and a selective fluorescence quencher to reduce the background signal. In the absence of miRNAs, HCR could not be triggered due to the stability of MB probes. The probes attached to the MoS2 surface, efficiently quenching fluorescence of the G-quadruplex/Thioflavin T. However, the presence of target miRNAs triggers the HCR process to generate large amount of HCR products. Meanwhile, the HCR products of long nanowires chain with abundant G-quadruplexes could not be adsorbed on the surface of MoS2, and therefore detach from the MoS2. Consequently, Thioflavin T could be embedded in G-quadruplexes and produced strong fluorescence signal. This fluorescence emission signal could achieve detection of miRNA as low as 4.2 pM and a wide linear ranges from 0.1 to 100 nM. In addition, a versatile fluorescence probe has been developed for detection of miRNA-21 by changing the miRNA-recognition domain of MB. Thus, the fluorescent probe would be a potential alternative tool for biomedical research and clinical molecular diagnostics.


Assuntos
Dissulfetos/química , Corantes Fluorescentes/química , Quadruplex G , MicroRNAs/análise , Sondas Moleculares/química , Molibdênio/química , Hibridização de Ácido Nucleico , Humanos
7.
Chem Commun (Camb) ; 55(52): 7510-7513, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31187817

RESUMO

Self-assembly of protein nanocages into two-dimensional superlattices can be achieved by disulfide-mediated modular interactions, which can be carried out by introducing single point mutation on the exterior surfaces of the protein nanocages nearby the symmetry rotation axes. As designed, the protein cages arrange in an on-axis alignment pattern.


Assuntos
Dissulfetos/química , Nanoestruturas/química , Proteínas/metabolismo , Cisteína/química , Ferritinas/genética , Ferritinas/metabolismo , Humanos , Oxirredução , Mutação Puntual , Proteínas/genética
8.
Chem Commun (Camb) ; 55(60): 8772-8775, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31172998

RESUMO

We introduced a new concept to the control of wetting characteristics by modulating the degree of atomic defects of two-dimensional transition metal dichalcogenide nanoassemblies of molybdenum disulfide. This work shed new light on the role of atomic vacancies on wetting characteristic that can be leveraged to develop a new class of superhydrophobic surfaces for various applications without altering their topography.


Assuntos
Adesão Celular , Dissulfetos/química , Células-Tronco Mesenquimais/fisiologia , Molibdênio/química , Nanoestruturas/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Molhabilidade
9.
Food Chem ; 297: 125005, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253325

RESUMO

Multiwalled carbon nanotubes molybdenum disulfide 3D nanocomposite (MWCNT-MoS2 NC) was successfully synthesized via eco-friendly hydrothermal method. The microstructural characterization of synthesized nanocomposite was carried out using different spectroscopic and microscopic techniques. Nanocomposite was activated using glutaraldehyde chemistry and used as a platform to immobilize Lens culinaris ß-galactosidase (Lsbgal) which resulted in 93% of immobilization efficiency. Attachment of Lsbgal onto nanocomposite was confirmed by AFM, FE-SEM, FTIR, and CLSM. The nanobiocatalyst showed broadening in operational pH and temperature working range. Remarkable increase in thermal stability was observed as compared to soluble enzyme. Nanobiocatalyst showed outstanding increase in storage stability, retained 92% of residual activity over a period of 8 months. This offers good reusability as it retained ∼50% residual activity up to 21 reuses and exhibited higher rate of lactose hydrolysis in whey. MWCNT-MoS2 NC conjugated to biomolecules can serve as a potential platform for fabrication of lactose biosensor.


Assuntos
Lactose/metabolismo , Lens (Planta)/enzimologia , Nanocompostos/química , Soro do Leite/metabolismo , beta-Galactosidase/metabolismo , Biocatálise , Dissulfetos/química , Estabilidade Enzimática , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Concentração de Íons de Hidrogênio , Molibdênio/química , Nanotubos de Carbono/química , Temperatura Ambiente , beta-Galactosidase/química
10.
Int J Nanomedicine ; 14: 3893-3909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239663

RESUMO

Background: Photothermal and chemotherapy treatment has been frequently studied for cancer therapy; however, chemotherapy is equally toxic to both normal and cancer cells. The clinical application value of most kinds of photothermal transforming agents remains limited, due to their poor degradation and minimal accumulation in tumors. Materials and methods: We reported the synthesis of photothermal transforming agents (MoS2) and chemotherapeutic (doxorubicin, DOX) co-loaded electrospun nanofibers using blend electrospinning for the treatment of postoperative tumor recurrence. Results: Under the irradiation of an 808 nm laser, the as-prepared chitosan/polyvinyl alcohol/MoS2/DOX nanofibers showed an admirable photothermal conversion capability with a photothermal conversion efficiency of 23.2%. These composite nanofibers are in vitro and in vivo biocompatible. In addition, they could control the sustained release of DOX and the generated heat can sensitize the chemotherapeutic efficacy of DOX via enhancing its release rate. Their chemo-/photothermal combined therapy efficiency was systematically studied in vitro and in vivo. Instead of circulating with the body fluid, MoS2 was trapped by the nanofibrous matrix in the tumor and so its tumor-killing ability was not compromised, thus rendering this composite nanofiber a promising alternative for future clinical translation within biomedical application fields. Conclusion: Chitosan/polyvinyl alcohol/MoS2/DOX nanofibers showed an excellent photothermal conversion capability with a photothermal conversion efficiency of 23.2% and can completely inhibit the postoperative tumor reoccurrence.


Assuntos
Dissulfetos/química , Doxorrubicina/uso terapêutico , Molibdênio/química , Nanofibras/química , Nanotecnologia/métodos , Neoplasias/terapia , Fototerapia , Animais , Materiais Biocompatíveis/farmacologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Reagentes para Ligações Cruzadas/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Células HT29 , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanofibras/ultraestrutura , Recidiva Local de Neoplasia/patologia , Neoplasias/sangue , Neoplasias/patologia , Neoplasias/cirurgia , Padrões de Referência , Resultado do Tratamento
11.
Food Chem ; 296: 9-16, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31202311

RESUMO

Z-lycopene isomers are more bioavailable than all-E-lycopene, especially 5-Z-lycopene. Based on our observations, the addition of unblanched onion could favor Z-isomerization of lycopene (by more than 94%) during heating tomato-onion-extra virgin olive oil (EVOO) purees at 90 °C for 2 h. The increase in Z-lycopene was correlated linearly with the addition of unblanched onion, with R2 > 0.92, and increased rates of 5-Z-lycopene were 3-4 times higher than for 9-Z-lycopene and 13-Z-lycopene. Diallyl disulfide (DADS), formed by alliinase-catalyzed breakdown of non-volatile precursors in onion, contributed to these increases and correlated linearly (R2 > 0.79, 0-0.50 mg/g puree) with increased Z-lycopene. Increased rates of 5-Z-lycopene were also 3-4 times higher than for 9-Z-lycopene and 13-Z-lycopene. However, blanching of onion, in tomato-onion-EVOO purees, before heating, significantly decreased the effect of onion on Z-isomerization of lycopene.


Assuntos
Lipídeos/química , Licopeno/química , Lycopersicon esculentum/química , Cebolas/química , Compostos Alílicos/química , Cromatografia Líquida de Alta Pressão , Dissulfetos/química , Isomerismo , Licopeno/análise , Lycopersicon esculentum/metabolismo , Azeite de Oliva/química , Cebolas/metabolismo , Temperatura Ambiente
12.
Nat Commun ; 10(1): 2745, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227705

RESUMO

Small molecule probes are indispensable tools to explore diverse cellular events. However, finding a specific probe of a target remains a high challenge. Here we report the discovery of Fast-TRFS, a specific and superfast fluorogenic probe of mammalian thioredoxin reductase, a ubiquitous enzyme involved in regulation of diverse cellular redox signaling pathways. By systematically examining the processes of fluorophore release and reduction of cyclic disulfides/diselenides by the enzyme, structural factors that determine the response rate and specificity of the probe are disclosed. Mechanistic studies reveal that the fluorescence signal is switched on by a simple reduction of the disulfide bond within the probe, which is in stark contrast to the sensing mechanism of published probes. The favorable properties of Fast-TRFS enable development of a high-throughput screening assay to discover inhibitors of thioredoxin reductase by using crude tissue extracts as a source of the enzyme.


Assuntos
Descoberta de Drogas/métodos , Corantes Fluorescentes/química , Imagem Molecular/métodos , Sondas Moleculares/química , Tiorredoxina Redutase 1/metabolismo , Animais , Produtos Biológicos/farmacologia , Misturas Complexas , Dissulfetos/química , Corantes Fluorescentes/metabolismo , Células HeLa , Ensaios de Triagem em Larga Escala/métodos , Humanos , Microscopia Intravital/métodos , Microscopia de Fluorescência/métodos , Sondas Moleculares/metabolismo , Oxirredução , RNA Interferente Pequeno/metabolismo , Proteínas Recombinantes/metabolismo , Especificidade por Substrato , Tiorredoxina Redutase 1/antagonistas & inibidores , Tiorredoxina Redutase 1/genética
13.
Chemosphere ; 232: 9-17, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31152908

RESUMO

Amorphous molybdenum sulphide materials are attracting more attention in heterogeneous catalysis, gas adsorption and water remediation fields. Herein, a new type of amorphous molybdenum sulphide composite (poly(diallyldimethylammonium-MoS4), shorten as PDADMA-MoS4) was synthesized via a facile precipitation reaction. Metal adsorption tests of prepared PDADMA-MoS4 composite shows that Hg2+ and Pb2+ concentrations in solution can decrease from 10 ppm to <0.5 ppb level much lower than the drinking water requirement (<2 ppb) in 10 min. The metal adsorption isotherms suggest that maximum metal-uptake capacities are 1460.0 mg/g for Hg (pH = 5) and 433.7 mg/g for Hg (pH = 1), indicating that this sorbent works over a wide pH range (1.0-7.0) to effectively remove Hg from aqueous solution. More importantly, at very low pH = 1, this sorbent material exhibits extraordinarily high selectivity of Hg over Pb and Cu (separation factors ßHg/Cu=4.5×104 and ßHg/Pb=3.6×104). The excellent Hg capacity and selectivity at low pH region (pH < 2) has shed light on the new generation of adsorbent materials for acidic wastewater treatment.


Assuntos
Dissulfetos/química , Mercúrio/análise , Molibdênio/química , Eliminação de Resíduos Líquidos , Águas Residuárias/química , Adsorção , Concentração de Íons de Hidrogênio , Metais
14.
Anal Bioanal Chem ; 411(21): 5481-5488, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31236648

RESUMO

The mechanism behind the variation in the photoluminescence (PL) of a MoS2 nanohybrid material with pH was investigated. Highly fluorescent MoS2 quantum dots dispersed across MoS2 nanosheets (MoS2 QDNS) were synthesized by a hydrothermal route in the presence of NaOH. Upon reducing the pH from 13 to 6.5, the PL intensity was markedly quenched. The removal of dangling sulfur atoms by adding mineral acids could be a plausible mechanism for this PL quenching, together with the inner filter effect and Förster resonance energy transfer due to the resulting species. A label-free turn-on fluorescence sensor for H2O2 was developed using this hybrid material. The PL of the acidified MoS2 QDNS at pH 6.5 increased (i.e., recovered) linearly with the concentration of H2O2. The dynamic range of the sensor was found to be 2-94 µM with a limit of detection (LOD) of 2 µM. This sensing strategy was also extended for the detection of glucose by appending glucose oxidase (GOx) as a catalyst. In the presence of GOx, glucose oxidizes to gluconic acid and H2O2, so the original level of glucose can be estimated by determining the H2O2 present. The absence of a complicated enzyme immobilization step is the prime advantage of the present glucose sensor. The current work exemplifies the utility of MoS2-based nanoparticle systems in the biological sensor domain. Graphical abstract.


Assuntos
Dissulfetos/química , Peróxido de Hidrogênio/análise , Concentração de Íons de Hidrogênio , Molibdênio/química , Transferência Ressonante de Energia de Fluorescência , Glucose Oxidase/análise , Limite de Detecção , Medições Luminescentes
15.
J Nanobiotechnology ; 17(1): 76, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31217009

RESUMO

BACKGROUND: Molybdenum disulfide (MoS2) has been widely explored for biomedical applications due to its brilliant photothermal conversion ability. In this paper, we report a novel multifunctional MoS2-based drug delivery system (MoS2-SS-HA). By decorating MoS2 nanosheets with hyaluronic acid (HA), these functionalized MoS2 nanosheets have been developed as a tumor-targeting chemotherapeutic nanocarrier for near-infrared (NIR) photothermal-triggered drug delivery, facilitating the combination of chemotherapy and photothermal therapy into one system for cancer therapy. RESULTS: The nanocomposites (MoS2-SS-HA) generated a uniform diameter (ca. 125 nm), exhibited great biocompatibility as well as high stability in physiological solutions, and could be loaded with the insoluble anti-cancer drug erlotinib (Er). The release of Er was greatly accelerated under near infrared laser (NIR) irradiation, showing that the composites can be used as responsive systems, with Er release controllable through NIR irradiation. MTT assays and confocal imaging results showed that the MoS2-based nanoplatform could selectively target and kill CD44-positive lung cancer cells, especially drug resistant cells (A549 and H1975). In vivo tumor ablation studies prove a better synergistic therapeutic effect of the joint treatment, compared with either chemotherapy or photothermal therapy alone. CONCLUSION: The functionalized MoS2 nanoplatform developed in this work could be a potent system for targeted drug delivery and synergistic chemo-photothermal cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Dissulfetos/química , Portadores de Fármacos/química , Cloridrato de Erlotinib/farmacologia , Hipertermia Induzida , Molibdênio/química , Nanocompostos/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Cloridrato de Erlotinib/química , Feminino , Humanos , Ácido Hialurônico/química , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fototerapia
16.
J Nanobiotechnology ; 17(1): 77, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226993

RESUMO

BACKGROUND: The design of efficient drug delivery vectors requires versatile formulations able to simultaneously direct a multitude of molecular targets and to bypass the endosomal recycling pathway of cells. Liposomal-based vectors need the decoration of the lipid surface with specific peptides to fulfill the functional requirements. The unspecific binding of peptides to the lipid surface is often accompanied with uncontrolled formulations and thus preventing the molecular mechanisms of a successful therapy. RESULTS: We present a simple synthesis pathway to anchor cysteine-terminal peptides to thiol-reactive lipids for adequate and quantitative liposomal formulations. As a proof of concept, we have synthesized two different lipopeptides based on (a) the truncated Fibroblast Growth Factor (tbFGF) for cell targeting and (b) the pH sensitive and fusogenic GALA peptide for endosomal scape. CONCLUSIONS: The incorporation of these two lipopeptides in the liposomal formulation improves the fibroblast cell targeting and promotes the direct delivery of cargo molecules to the cytoplasm of the cell.


Assuntos
Dissulfetos/química , Lipídeos/química , Peptídeos/química , Piridinas/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Cisteína/química , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos , Endossomos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Lipossomos/química , Camundongos , Estrutura Molecular , Imagem Óptica/métodos , Estudo de Prova de Conceito
17.
Phys Chem Chem Phys ; 21(22): 11916-11923, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31125036

RESUMO

Peptide structural transformation and aggregation is associated with a large number of outsider aetiology diseases, and it is intrinsically linked to amyloid peptide aggregation. Diphenylalanine self-assembled structures are used as robust minimalist beta amyloids not only to elucidate protein aggregation but also to generate hydrogels. Herein, we employed a neutral model peptide Ac-Phe-Phe-Cys-NH2 (Ac-FFC-NH2) to elucidate the role of intermolecular disulfide bonds in protein fibrillation. The Ac-FFC-NH2 peptide initially self-assembles into nanospheres that evolve to amyloid type fibrils under mild oxidative conditions. Incubation of the peptide in the presence of the chemical reduction agent TCEP inhibits the formation of the fibrils, detecting only spherical nanostructures with no secondary structure. Importantly, we triggered the transformation of the preformed linear straight amyloid fibrils to non-fibrillar structures by TCEP treatment. Under this condition, the amyloid bundles are transformed into rings, which evolve to a new spherical microstructure. We showed that the chemical reduction of intermolecular S-S in internal amyloid sequences might favour the off-path intermediates of amyloid fibril growth, even when the fibrils are formed. Our findings demonstrated that in internal amyloid sequences, the formation of intermolecular S-S promotes the formation of amyloid type fibrils; meanwhile, its reduction stabilises non-fibrillar structures. Altogether, this work provides fundamental understanding at the molecular and supramolecular level, thus facilitating the rational design of therapeutic tools for protein aggregation diseases.


Assuntos
Amiloide/química , Dissulfetos/química , Oligopeptídeos/química , Oligopeptídeos/síntese química , Oxirredução , Multimerização Proteica
18.
Molecules ; 24(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067724

RESUMO

One of the most challenging issues in photocatalytic hydrogen evolution is to efficiently separate photocharge carriers. Although MoS2 loading could effectively improve the photoactivity of TiO2, a fundamental understanding of the charge transfer process between TiO2 and MoS2 is still lacking. Herein, TiO2 photocatalysts with different exposed facets were used to construct MoS2/TiO2 heterostructures. XPS, ESR, together with PL measurements evidenced the Type II electron transfer from MoS2 to {001}-TiO2. Differently, electron-rich characteristic of {101}-faceted TiO2 were beneficial for the direct Z-scheme recombination of electrons in TiO2 with holes in MoS2. This synergetic effect between facet engineering and oxygen vacancies resulted in more than one order of magnitude enhanced hydrogen evolution rate. This finding revealed the elevating mechanism of constructing high-performance MoS2/TiO2 heterojunction based on facet and defect engineering.


Assuntos
Dissulfetos/química , Transporte de Elétrons , Hidrogênio/química , Molibdênio/química , Titânio/química , Catálise , Oxigênio/química , Processos Fotoquímicos
19.
J Agric Food Chem ; 67(27): 7775-7782, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31088053

RESUMO

Analyzing an in vitro gastroduodenal digest of whey proteins by high-performance liquid chromatography (HPLC) coupled to high-resolution/high-sensitivity tandem mass spectrometry (MS/MS), we sought to evaluate if state-of-art peptidomics provide comprehensive peptide coverage of food "digestomes". A multitude of small-sized peptides derived from both α-lactalbumin and ß-lactoglobulin as well as disulfide cross-linked hetero-oligomers remained unassigned, even when the digests were compared before and after S-S reduction. The precipitation with 12% trichloroacetic acid demonstrated the occurrence of large-sized polypeptides that escaped the bioinformatic identification. The analysis of a HPLC-MS/MS run with different proteomic search engines generated dissimilar peptide subsets, thus emphasizing the demand of refined searching algorithms. Although the MS/MS fragmentation of monocharged ions with exclusion of non-peptide-interfering compounds enlarged the inventory of short peptides, the overall picture of the "digestome" was still incomplete. These findings raise relevant implications for the identification of possible food-derived bioactive peptides or allergenic determinants.


Assuntos
Digestão , Duodeno/metabolismo , Mucosa Gástrica/metabolismo , Peptídeos/análise , Proteínas do Soro do Leite/química , Proteínas do Soro do Leite/metabolismo , Alérgenos/análise , Cromatografia Líquida de Alta Pressão/métodos , Dissulfetos/química , Análise de Alimentos/métodos , Lactalbumina/química , Lactalbumina/metabolismo , Lactoglobulinas/química , Lactoglobulinas/metabolismo , Proteólise , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos
20.
Nanoscale ; 11(18): 9185-9193, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31038146

RESUMO

Recent advances in nanotechnology have developed a lot of opportunities for biological applications. In this work, multifunctional MoS2/AuNR nanocomposites with unique high NIR absorption were designed via combining MoS2 nanosheets and gold nanorods (AuNRs). The nanocomposites were synthesized through electrostatic self-assembly and showed high stability and good biocompatibility. Then they were used to modulate the aggregation of amyloid-ß peptides, destabilize mature fibrils under NIR irradiation, and eliminate Aß-induced ROS against neurotoxicity. The inhibition and destabilization effects were confirmed by Thioflavin T (ThT) fluorescence assay and transmission electron microscopy (TEM). Cell viability assay and ROS assay revealed that MoS2/AuNR nanocomposites could alleviate Aß-induced oxidative stress and cell toxicity. More importantly, both MoS2 nanosheets and AuNRs can be used as NIR photothermal agents, MoS2/AuNR nanocomposites have enhanced ability of disrupting Aß fibrils and improved cell viability by generating local heat under low power NIR irradiation. Our results provide new insights into the design of new multifunctional systems for the treatment of amyloid-related diseases.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Raios Infravermelhos , Nanocompostos/química , Fragmentos de Peptídeos/metabolismo , Amiloide/química , Amiloide/toxicidade , Peptídeos beta-Amiloides/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dissulfetos/química , Ouro/química , Humanos , Molibdênio/química , Nanocompostos/toxicidade , Nanotubos/química , Fragmentos de Peptídeos/química , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
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