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1.
Chem Commun (Camb) ; 56(20): 3035-3038, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32048636

RESUMO

It remains challenging to develop new materials exhibiting enzyme-like activities and understand the structure-property correlations and catalytic mechanisms. In this study, the characteristics, mechanisms, and applications of a light-activated mimic oxidase based on semiconducting polymer dots (Pdots) prepared from an organic conjugated polymer are demonstrated.


Assuntos
Luz , Polímeros/química , Pontos Quânticos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Catálise , Estrutura Molecular , Oxirredutases/química , Oxirredutases/metabolismo , Semicondutores
2.
Top Curr Chem (Cham) ; 378(1): 8, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31840194

RESUMO

Plasmonic nanoparticles (NPs) are one of the most promising and studied inorganic nanomaterials for different biomedical applications. Plasmonic NPs have excellent biocompatibility, long-term stability against physical and chemical degradation, relevant optical properties, well-known synthesis methods and tuneable surface functionalities. Herein, we review recently reported bioconjugated plasmonic NPs using different chemical approaches and loading cargoes (such as drugs, genes, and proteins) for enhancement of transdermal delivery across biological tissues. The main aim is to understand the interaction of the complex skin structure with biomimetic plasmonic NPs. This knowledge is not only important in enhancing transdermal delivery of pharmaceutical formulations but also for controlling undesired skin penetration of industrial products, such as cosmetics, sunscreen formulations and any other mass-usage consumable that contains plasmonic NPs.


Assuntos
Nanopartículas/química , Pele/metabolismo , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Materiais Biomiméticos/farmacologia , Portadores de Fármacos/química , Ouro/química , Humanos , Nanopartículas Metálicas/química , Nanopartículas/metabolismo , Pele/efeitos dos fármacos
3.
Chem Commun (Camb) ; 55(96): 14534-14537, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31740902

RESUMO

Fe-N/C single atom catalysts (SACs) exhibit peroxidase-like, oxidase-like, catalase-like, and glutathione peroxidase-like activity. Fe-N/C SACs are successfully applied to control the intracellular H2O2 level. This study not only explores the types of SACs mimicking enzymes but also provides opportunities for SACs in biomedical and other bioengineering applications.


Assuntos
Materiais Biomiméticos/química , Carbono/química , Ferro/química , Nitrogênio/química , Espécies Reativas de Oxigênio/química , Materiais Biomiméticos/metabolismo , Materiais Biomiméticos/farmacologia , Catalase/química , Catalase/metabolismo , Catálise , Sobrevivência Celular/efeitos dos fármacos , Glutationa Peroxidase/química , Glutationa Peroxidase/metabolismo , Células HeLa , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Oxirredução , Porfirinas/química , Espécies Reativas de Oxigênio/metabolismo
4.
Chem Commun (Camb) ; 55(87): 13152-13155, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31617527

RESUMO

We designed a supported lipid bilayer (SLB) biomimetic membrane system that comprised polyaniline (PANI) to support a lipid bilayer membrane that incorporated Na+/H+ transporter proteins (NhaA) to give the system the capability of controllable electrogenic ion transport. The high turnover rate of NhaA (∼105 per min) provides the basis for this PANI-SLB-NhaA system to be a high-speed rechargeable biocapacitor that functions as a low-energy-consuming fast switch for biological engineering applications.


Assuntos
Compostos de Anilina/metabolismo , Materiais Biomiméticos/metabolismo , Técnicas Biossensoriais , Proteínas de Escherichia coli/metabolismo , Bicamadas Lipídicas/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Compostos de Anilina/química , Materiais Biomiméticos/química , Espectroscopia Dielétrica , Eletrodos , Proteínas de Escherichia coli/química , Ouro/química , Ouro/metabolismo , Bicamadas Lipídicas/química , Trocadores de Sódio-Hidrogênio/química
5.
Chemistry ; 25(63): 14267-14272, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31603595

RESUMO

Bioinspired complexes employing the ligands 6-tert-butylpyridazine-3-thione (SPn) and pyridine-2-thione (SPy) were synthesized and fully characterized to mimic the tungstoenzyme acetylene hydratase (AH). The complexes [W(CO)(C2 H2 )(CHCH-SPy)(SPy)] (4) and [W(CO)(C2 H2 )(CHCH-SPn)(SPn)] (5) were formed by intramolecular nucleophilic attack of the nitrogen donors of the ligand on the coordinated C2 H2 molecule. Labelling experiments using C2 D2 with the SPy system revealed the insertion reaction proceeding via a bis-acetylene intermediate. The starting complex [W(CO)(C2 H2 )(SPy)2 ] (6) for these studies was accessed by the new acetylene precursor mixture [W(CO)(C2 H2 )n (MeCN)3-n Br2 ] (n=1 and 2; 7). All complexes represent rare examples in the field of W-C2 H2 chemistry with 4 and 5 being the first of their kind. In the ongoing debate on the enzymatic mechanism, the findings support activation of acetylene by the tungsten center.


Assuntos
Materiais Biomiméticos/química , Complexos de Coordenação/química , Tungstênio/química , Acetileno/química , Acetileno/metabolismo , Materiais Biomiméticos/metabolismo , Complexos de Coordenação/síntese química , Medição da Troca de Deutério , Hidroliases/química , Hidroliases/metabolismo , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estereoisomerismo
6.
Chemistry ; 25(63): 14290-14294, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31448834

RESUMO

The reactivity of the previously reported peroxo adduct [FeIII 2 (µ-O2 )(MeBzim-Py)4 (CH3 CN)2 ]4+ (1) (MeBzim-Py=2-(2'-pyridyl)-N-methylbenzimidazole) towards aldehyde substrates including phenylacetaldehyde (PAA), hydrocinnamaldehyde (HCA), propionaldehyde (PA), 2-phenylpropionaldehyde (PPA), cyclohexanecarboxaldehyde (CCA), and para-substituted benzaldehydes (benzoyl chlorides) has been investigated. Complex 1 proved to be a nucleophilic oxidant in aldehyde deformylation reaction. These models, including detailed kinetic and mechanistic studies, may serve as the first biomimics of aldehyde deformylating oxygenase (ADO) enzymes.


Assuntos
Aldeídos/química , Materiais Biomiméticos/química , Complexos de Coordenação/química , Compostos Férricos/química , Materiais Biomiméticos/metabolismo , Complexos de Coordenação/metabolismo , Cinética , Oxigenases/química , Oxigenases/metabolismo
7.
Chemistry ; 25(63): 14370-14381, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31469197

RESUMO

Creating efficient and residue-directed artificial proteases is a challenging task due to the extreme inertness of the peptide bond, combined with the difficulty of achieving specific interactions between the catalysts and the protein side chains. Herein we report strictly site-selective hydrolysis of a multi-subunit globular protein, hemoglobin (Hb) from bovine blood, by a range of ZrIV -substituted polyoxometalates (Zr-POMs) in mildly acidic and physiological pH solutions. Among 570 peptide bonds in Hb, selective cleavage was observed at only eleven sites, each occurring at Asp-X peptide bonds located in the positive patches on the protein surface. The molecular origins of the observed Asp-X selectivity were rationalized by means of molecular docking, DFT-based binding, and mechanistic studies on model peptides. The proposed mechanism of hydrolysis involves coordination of the amide oxygen to ZrIV followed by a direct nucleophilic attack of the side chain carboxylate group on the C-terminal amide carbon atom with formation of a cyclic anhydride, which is further hydrolyzed to give the reaction products. The activation energy for the cleavage of the structurally related Glu-X sequence compared to Asp-X was calculated to be higher by 1.4 kcal mol-1 , which corresponds to a difference of about one order of magnitude in the rates of hydrolysis. The higher activation energy is attributed to the higher strain present in the six-membered ring of glutaric anhydride (Glu-X), as compared to the five-membered ring of the succinic anhydride (Asp-X) intermediate. Similarly, the cleavage at X-Asp and X-Glu bonds are predicted to be kinetically less likely as the corresponding activation energies were 6 kcal mol-1 higher, explaining the experimentally observed selectivity. The synergy between the negatively charged polyoxometalate cluster, which binds at positive patches on protein surfaces, and selective activation of Asp-X peptide bonds located in these regions by ZrIV ions, results in a novel class of artificial proteases with aspartate-directed reactivity, which is very rare among naturally occurring proteases.


Assuntos
Ácido Aspártico/química , Materiais Biomiméticos/química , Complexos de Coordenação/química , Compostos de Tungstênio/química , Zircônio/química , Sequência de Aminoácidos , Sítios de Ligação , Materiais Biomiméticos/metabolismo , Catálise , Complexos de Coordenação/metabolismo , Hemoglobinas/química , Hemoglobinas/metabolismo , Hidrólise , Espectroscopia de Ressonância Magnética , Conformação Molecular , Simulação de Acoplamento Molecular , Peptídeo Hidrolases/química , Peptídeo Hidrolases/metabolismo , Termodinâmica
8.
Biomater Sci ; 7(8): 3425-3437, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31268061

RESUMO

Since conventional chemotherapy has a variety of deficiencies and severe side effects, phototherapy has recently aroused great interest worldwide owing to its great potential towards theranostic applications. However, the physiological barrier of tumors hindered the penetration of therapeutic and imaging agents into the center of tumors. In this study, a novel biomimetic nanoplatform inspired by high-density lipoproteins (HDLs) was designed with deep tumor penetrating ability and integrated the clinical imaging agent indocyanine green (ICG) for synergistic phototherapy. Specifically, the HDL-protein was conjugated with the tumor-homing iRGD peptide via an applicable cross-linker to obtain a similar α helix structure, which served as an organizing scaffold for maintaining lipid nanoparticle structure. Our study illustrated that the mimicking nanoparticles shared nanosized diameters and superior biostability compared with free ICG. Once irradiated by NIR light, the encapsulated ICG could produce heat in localized ranges for photothermal therapy (PTT) and sufficient reactive oxygen species (ROS) for photodynamic therapy (PDT). Moreover, the fluorescence of ICG excited by NIR light effectively assisted in diagnosis. After intravenous injection, HDL mimicking nanoparticles could penetrate into deep tumors to realize enhanced phototherapy (PTT and PDT) under NIR laser irradiation. This biomimetic drug delivery system could open an avenue for the production of tailored theranostic nanoplatforms for personalized medicine in the near future.


Assuntos
Materiais Biomiméticos/química , Verde de Indocianina/química , Lipoproteínas HDL/metabolismo , Imagem Molecular/métodos , Nanopartículas/química , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Animais , Transporte Biológico , Materiais Biomiméticos/metabolismo , Linhagem Celular Tumoral , Verde de Indocianina/metabolismo , Espaço Intracelular/metabolismo , Camundongos , Oligopeptídeos/química , Espécies Reativas de Oxigênio/metabolismo
9.
Biomater Sci ; 7(9): 3706-3716, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31187794

RESUMO

Tumor hypoxia, which is indispensable to tumor propagation and therapy resistance, has been one of the most important factors influencing clinical outcomes. To modulate the hypoxia microenvironment, we herein developed reactive oxygen species (ROS)-sensitive arylboronic ester-based biomimetic nanocarriers co-encapsulated with a photosensitizer chlorin e6 (Ce6) and a hypoxia-activated prodrug tirapazamine (TPZp) for tumor-specific release and synergistic photodynamic chemotherapy. In order to bypass macrophage uptake and improve tumor penetration, the nanocarriers were further modified with the red blood cell membrane and iRGD peptide (denoted as NPs@i-RBMCe6+TPZp). After administration, NPs@i-RBMCe6+TPZp exhibited prolonged blood circulation, selective tumor accumulation and excellent penetration into the tumor interior. Upon light irradiation, ROS were generated by Ce6 for photodynamic therapy (PDT), which subsequently caused dissociation of the ROS-responsive nanocarriers. An enhanced therapeutic effect was further achieved through the activation of TPZp in the aggravated local hypoxia microenvironment. The synergistic cancer therapy based on NPs@i-RBMCe6+TPZp significantly suppressed tumor growth with negligible side effects. The biomimetic nanocarriers have great potential to overcome hypoxia-limited PDT, and significantly improve the anticancer efficacy by synergistic tumor-targeted PDT and hypoxia-activated chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Materiais Biomiméticos/química , Neoplasias da Mama/tratamento farmacológico , Hipóxia Celular/efeitos dos fármacos , Nanopartículas/química , Fotoquimioterapia , Espécies Reativas de Oxigênio/metabolismo , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Materiais Biomiméticos/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Camundongos , Estrutura Molecular , Nanopartículas/metabolismo , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Relação Estrutura-Atividade , Tirapazamina/química , Tirapazamina/farmacologia
10.
Nat Commun ; 10(1): 2223, 2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-31110174

RESUMO

Mammalian cells are different from plant and microbial cells, having no exterior cell walls for protection. Environmental assaults can easily damage or destroy mammalian cells. Thus, the ability to develop a biomimetic cell wall (BCW) on their plasma membrane as a shield can advance various applications. Here we demonstrate the synthesis of BCW with a framing template and a crosslinked matrix for shielding live mammalian cells. The framing template is a supramolecular DNA structure. The crosslinked matrix is a polyelectrolyte complex made of alginate and polylysine. As the entire procedure of BCW synthesis is strictly operated under physiological conditions, BCW-covered mammalian cells can maintain high bioactivity. More importantly, the data show that BCW can shield live mammalian cells from not only physical assaults but also biological assaults. Thus, this study has successfully demonstrated the synthesis of BCW on live mammalian cells with great potential of shielding them from environmental assaults.


Assuntos
Materiais Biomiméticos/metabolismo , Parede Celular/metabolismo , DNA/metabolismo , Nanocápsulas/química , Alginatos/química , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Parede Celular/ultraestrutura , Reagentes para Ligações Cruzadas/química , Humanos , Microscopia Eletrônica de Transmissão , Nanocápsulas/ultraestrutura , Polilisina/química
11.
Mikrochim Acta ; 186(5): 295, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31016397

RESUMO

A metal organic framework (MOF) of type Fe(III)-BTC (where BTC is 1,3,5-benzenetricarboxylic acid) was utilized to construct an integrated system for cascade colorimetric determination of glucose. The MOF performs a dual function in acting (a) as a peroxidase (POx) mimic, and (b) as a solid support for immobilization of glucose oxidase (GOx). The MOF was prepared by a one-pot method. Glucose is consumed while H2O2 is produced during the enzymatic oxidation by GOx. In the presence of H2O2, the POx mimic catalytically oxidizes 3,3',5,5'-tetramethylbenzidine (TMB) to form a blue-green product. The absorbance of oxidized TMB (measured at 652 nm) increases linearly in the 5.0-100 µM glucose concentration range, and the detection limit is 2.4 µM. The GOx@Fe-BTC MOF was successfully applied to the determination of glucose in serum. Graphical abstract Schematic presentation of a bifunctional metal organic framework of type Fe-BTC for cascade (enzymatic and enzyme-mimicking) colorimetric determination of glucose. The Fe-BTC performs a dual function in acting as both a peroxidase mimic and support for immobilizing glucose oxidase. Using the integrated enzyme, a colorimetric method was successfully applied to one-step detection of glucose in human serum.


Assuntos
Corantes/química , Glucose/análise , Ferro/química , Estruturas Metalorgânicas/química , Ácidos Tricarboxílicos/química , Benzidinas/química , Materiais Biomiméticos/metabolismo , Técnicas Biossensoriais/métodos , Catálise , Cor , Colorimetria , Glucose Oxidase/metabolismo , Peróxido de Hidrogênio , Limite de Detecção , Oxirredução , Peroxidases/metabolismo
12.
Biopolymers ; 110(6): e23277, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30972750

RESUMO

Surfactant protein C (SP-C) is an important constituent of lung surfactant (LS) and, along with SP-B, is included in exogenous surfactant replacement therapies for treating respiratory distress syndrome (RDS). SP-C's biophysical activity depends upon the presence of a rigid C-terminal helix, of which the secondary structure is more crucial to functionality than precise side-chain chemistry. SP-C is highly sequence-conserved, suggesting that the ß-branched, aliphatic side chains of the helix are also important. Nonnatural mimics of SP-C were created using a poly-N-substituted glycine, or "peptoid," backbone. The mimics included varying amounts of α-chiral, aliphatic side chains and α-chiral, aromatic side chains in the helical region, imparting either biomimicry or structural rigidity. Biophysical studies confirmed that the peptoids mimicked SP-C's secondary structure and replicated many of its surface-active characteristics. Surface activity was optimized by incorporating both structurally rigid and biomimetic side chain chemistries in the helical region indicating that both characteristics are important for activity. By balancing these features in one mimic, a novel analogue was created that emulates SP-C's in vitro surface activity while overcoming many of the challenges related to natural SP-C. Peptoid-based analogues hold great potential for use in a synthetic, biomimetic LS formulation for treating RDS.


Assuntos
Materiais Biomiméticos/química , Peptoides/química , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/metabolismo , Dicroísmo Circular , Desenho de Drogas , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Microscopia de Fluorescência , Peptoides/síntese química , Peptoides/metabolismo , Conformação Proteica em alfa-Hélice , Precursores de Proteínas/química , Proteolipídeos/química , Propriedades de Superfície
13.
Adv Mater ; 31(19): e1900401, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30920710

RESUMO

2D nanomaterials have attracted broad interest in the field of biomedicine owing to their large surface area, high drug-loading capacity, and excellent photothermal conversion. However, few studies report their "enzyme-like" catalytic performance because it is difficult to prepare enzymatic nanosheets with small size and ultrathin thickness by current synthetic protocols. Herein, a novel one-step wet-chemical method is first proposed for protein-directed synthesis of 2D MnO2 nanosheets (M-NSs), in which the size and thickness can be easily adjusted by the protein dosage. Then, a unique sono-chemical approach is introduced for surface functionalization of the M-NSs with high dispersity/stability as well as metal-cation-chelating capacity, which can not only chelate 64 Cu radionuclides for positron emission tomography (PET) imaging, but also capture the potentially released Mn2+ for enhanced biosafety. Interestingly, the resulting M-NS exhibits excellent enzyme-like activity to catalyze the oxidation of glucose, which represents an alternative paradigm of acute glucose oxidase for starving cancer cells and sensitizing them to thermal ablation. Featured with outstanding phototheranostic performance, the well-designed M-NS can achieve effective photoacoustic-imaging-guided synergistic starvation-enhanced photothermal therapy. This study is expected to establish a new enzymatic phototheranostic paradigm based on small-sized and ultrathin M-NSs, which will broaden the application of 2D nanomaterials.


Assuntos
Compostos de Manganês/química , Nanoestruturas/química , Neoplasias/diagnóstico , Neoplasias/terapia , Óxidos/química , Fototerapia/métodos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/metabolismo , Catálise , Linhagem Celular Tumoral , Meios de Contraste/química , Cobre/química , Humanos , Marcação por Isótopo/métodos , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Oxirredução/efeitos dos fármacos , Tamanho da Partícula , Tomografia por Emissão de Pósitrons/métodos , Propriedades de Superfície , Nanomedicina Teranóstica/métodos , Água/química
14.
Proc Natl Acad Sci U S A ; 116(12): 5405-5410, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30833393

RESUMO

Biomimetic systems often exhibit striking designs well adapted to specific functions that have been inspiring the development of new technologies. Herein, we explored the remarkable ability of honey bees to catch and release large quantities of pollen grains. Hair spacing and height on bees are crucial for their ability to mechanically fix pollen grains. Inspired by this, we proposed the concept of a micropatterned surface for microparticle entrapment, featuring high-aspect-ratio elastic micropillars spaced to mimic the hairy surface of bees. The hypothesis was validated by investigating the ability of polydimethylsiloxane microfabricated patches to fix microparticles. The geometrical arrangement, spacing, height, and flexibility of the fabricated micropillars, and the diameter of the microparticles, were investigated. Higher entrapment capability was found through the match between particle size and pillar spacing, being consistent with the observations that the diameter of pollen grains is similar to the spacing between hairs on bees' legs. Taller pillars permitted immobilization of higher quantities of particles, consistent with the high aspect ratio of bees' hairs. Our biomimetic surfaces were explored for their ability to fix solid microparticles for drug-release applications, using tetracycline hydrochloride as a model antibiotic. These surfaces allowed fixation of more than 20 mg/cm2 of antibiotic, about five times higher dose than commercialized patches (5.1 mg/cm2). Such bioinspired hairy surfaces could find applications in a variety of fields where dry fixation of high quantities of micrometer-sized objects are needed, including biomedicine, agriculture, biotechnology/chemical industry, and cleaning utensils.


Assuntos
Abelhas/ultraestrutura , Materiais Biomiméticos/metabolismo , Portadores de Fármacos/química , Polinização , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Portadores de Fármacos/metabolismo , Escherichia coli/efeitos dos fármacos , Pólen , Staphylococcus aureus/efeitos dos fármacos
15.
Nat Protoc ; 14(4): 991-1014, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30886367

RESUMO

Developing a mechanistic understanding of the impact of food structure and composition on human health has increasingly involved simulating digestion in the upper gastrointestinal tract. These simulations have used a wide range of different conditions that often have very little physiological relevance, and this impedes the meaningful comparison of results. The standardized protocol presented here is based on an international consensus developed by the COST INFOGEST network. The method is designed to be used with standard laboratory equipment and requires limited experience to encourage a wide range of researchers to adopt it. It is a static digestion method that uses constant ratios of meal to digestive fluids and a constant pH for each step of digestion. This makes the method simple to use but not suitable for simulating digestion kinetics. Using this method, food samples are subjected to sequential oral, gastric and intestinal digestion while parameters such as electrolytes, enzymes, bile, dilution, pH and time of digestion are based on available physiological data. This amended and improved digestion method (INFOGEST 2.0) avoids challenges associated with the original method, such as the inclusion of the oral phase and the use of gastric lipase. The method can be used to assess the endpoints resulting from digestion of foods by analyzing the digestion products (e.g., peptides/amino acids, fatty acids, simple sugars) and evaluating the release of micronutrients from the food matrix. The whole protocol can be completed in ~7 d, including ~5 d required for the determination of enzyme activities.


Assuntos
Materiais Biomiméticos/metabolismo , Ingredientes de Alimentos/análise , Intestinos/enzimologia , Modelos Biológicos , Boca/enzimologia , Estômago/enzimologia , Aminoácidos/análise , Aminoácidos/química , Bile/enzimologia , Materiais Biomiméticos/química , Digestão/fisiologia , Ingestão de Alimentos/fisiologia , Ensaios Enzimáticos/normas , Ácidos Graxos/análise , Ácidos Graxos/química , Alimentos , Suco Gástrico/enzimologia , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Oligossacarídeos/análise , Oligossacarídeos/química , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/química , Saliva/enzimologia
16.
Int J Mol Sci ; 20(5)2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30813553

RESUMO

Rhamnolipids (RLs) are potential biocontrol agents for crop culture protection. Their mode of action has been proposed as dual, combining plant protection activation and antifungal activities. The present work focuses on the interaction of natural RLs with plant and fungi membrane models at the molecular scale. Representative models were constructed and the interaction with RLs was studied by Fourier transform infrared (FTIR) and deuterium nuclear magnetic resonance (²H NMR) spectroscopic measurements. Molecular dynamic (MD) simulations were performed to investigate RL insertion in lipid bilayers. Our results showed that the RLs fit into the membrane models and were located near the lipid phosphate group of the phospholipid bilayers, nearby phospholipid glycerol backbones. The results obtained with plant plasma membrane models suggest that the insertion of RLs inside the lipid bilayer did not significantly affect lipid dynamics. Oppositely, a clear fluidity increase of fungi membrane models was observed. This effect was related to the presence and the specific structure of ergosterol. The nature of the phytosterols could also influence the RL effect on plant plasma membrane destabilization. Subtle changes in lipid dynamics could then be linked with plant defense induction and the more drastic effects associated with fungal membrane destabilization.


Assuntos
Materiais Biomiméticos/metabolismo , Biofísica , Membrana Celular/metabolismo , Fungos/metabolismo , Glicolipídeos/metabolismo , Plantas/metabolismo , Fenômenos Biomecânicos , Glicolipídeos/química , Bicamadas Lipídicas/metabolismo , Espectroscopia de Ressonância Magnética , Simulação de Dinâmica Molecular , Fosfolipídeos/metabolismo
17.
Eur J Med Chem ; 166: 281-290, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30731397

RESUMO

Offering novel scaffolds targeting estrogen receptor creates huge necessity to overcome the evolving resistance developed by tumors. Structure-based drug design coupled with ring opening strategy of the steroids skeleton revealed the potential of indole-based analogs to be synthesized targeting the ligand binding domain of estrogen receptor-α. In vitro studies revealed the potential of the total sub-classes of the synthesized analogs to show anti-proliferative activity against estrogen receptor-dependent cancer cell lines at IC50 ranging from 28.23 to 57.13 µM. This was further validated by evaluating the potential of the synthesized analogs to compete along with estradiol via ER-α ELISA assay to show inhibitory profile at IC50 ranging from 1.76 to 204.75 nM. Two analogs (YMA-005 and YMA-006) showed significant reduction in tumor size at two dose levels with extensive degeneration and necrosis. Both YMA-005 and YMA-006 showed in-situ reduction of ER-α Immunohistochemical expression at both dose levels. Ultimately, novel analogs of indole-based biomimetic of estrone scaffolds were offered as estrogen receptor-α inhibitors.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/farmacologia , Desenho de Drogas , Receptor alfa de Estrogênio/antagonistas & inibidores , Indóis/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Linhagem Celular Tumoral , Técnicas de Química Sintética , Receptor alfa de Estrogênio/química , Receptor alfa de Estrogênio/metabolismo , Humanos , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Conformação Proteica
18.
Chem Asian J ; 14(7): 1021-1027, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30809935

RESUMO

Glycopolymers mimicking GM1 gangliosides were synthesized by incorporating multiple types of carbohydrates into the polymer backbone. The glycopolymers were immobilized onto gold surfaces, and the interactions with the cholera toxin B subunit (CTB) were analyzed using surface plasmon resonance imaging. The glycopolymer containing both galactose and neuraminic acid showed enhanced recognition of CTB. The interaction was enhanced mainly because of an improvement in the dissociation process by the binding of the neuraminic acid group in the GM1 binding pocket. This cooperativity of galactose and neuraminic acid was achieved by incorporation into the same flexible polymer backbone, and the importance of the close placement of galactose and neuraminic acid groups was revealed. These results will be valuable in medical fields and also for the development of biofunctional materials.


Assuntos
Resinas Acrílicas/metabolismo , Materiais Biomiméticos/metabolismo , Toxina da Cólera/metabolismo , Galactose/metabolismo , Ácidos Neuramínicos/metabolismo , Resinas Acrílicas/síntese química , Resinas Acrílicas/química , Materiais Biomiméticos/síntese química , Gangliosídeo G(M1)/química , Gangliosídeo G(M1)/metabolismo , Glicosilação , Ouro/química , Cinética , Ligação Proteica , Ressonância de Plasmônio de Superfície
19.
ACS Appl Mater Interfaces ; 11(8): 7850-7861, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30707559

RESUMO

Biomimetic nanoparticles (NPs) combine the flexibility and reproducibility of synthetic materials with the functionality of biological materials. Here, we developed and characterized biomimetic poly(lactic- co-glycolic acid) (PLGA) NPs coated with human cancer cell membrane fractions (CCMFs) to form CCMF-coated PLGA (CCMF-PLGA) NPs. We evaluated the ability of these CCMF-PLGA NPs to disrupt cancer cell-stromal cell interactions and to induce an immune response. Western blot analysis verified the plasma membrane purity of CCMFs. Confocal fluorescence microscopy and flow cytometry confirmed the presence of intact membrane-associated proteins including CXCR4 and CD44 following membrane derivation and coating. CCMFs and CCMF-PLGA NPs were capable of inhibiting cancer cell migration toward human mammary fibroblasts. Intravenous injection of CCMF-PLGA NPs significantly reduced experimental metastasis in vivo. Following immunization of Balb/c mice, near-infrared fluorescence imaging confirmed the migration of NPs to proximal draining lymph nodes (LNs). A higher percentage of CD8+ and CD4+ cytotoxic T-lymphocyte populations was observed in spleens and LNs of CCMF-PLGA NP-immunized mice. Splenocytes isolated from CCMF-PLGA NP-immunized mice had the highest number of interferon gamma-producing T-cells as detected by the ELISpot assay. CCMF-PLGA NPs hold promise for disrupting cancer cell-stromal cell interactions and for priming the immune system in cancer immunotherapy.


Assuntos
Materiais Biomiméticos/uso terapêutico , Membrana Celular/química , Neoplasias Pulmonares/prevenção & controle , Nanopartículas/química , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Materiais Biomiméticos/farmacologia , Neoplasias da Mama/patologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Receptores de Hialuronatos/química , Interferon gama/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Linfonodos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Receptores CXCR4/química
20.
ACS Appl Mater Interfaces ; 11(6): 5804-5811, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30663882

RESUMO

Metal-peptide interactions provide plentiful resource and design principles for developing functional biomaterials and smart sensors. Pb2+, as a borderline metal ion, has versatile coordination modes. The interference from competing metal ions and endogenous chelating species greatly challenges Pb2+ analysis, especially in complicated living biosystems. Herein, a biomimetic peptide-based fluorescent sensor GSSH-2TPE was developed, starting from the structure of a naturally occurring peptide glutathione. Lewis acid-base theory was employed to guide the molecular design and tune the affinity and selectivity of the targeting performance. The integration of peptide recognition and aggregation-induced emission effect provides desirable sensing features, including specific turn-on response to Pb2+ over 18 different metal ions, rapid binding, and signal output, as well as high sensitivity with a detection limit of 1.5 nM. Mechanism investigation demonstrated the balance between the chelating groups, and the molecular configuration of the sensor contributes to the high selectivity toward Pb2+ complexation. The ion-induced supramolecular assembly lights up the bright fluorescence. The ability to image Pb2+ in living cells was exhibited with minimal interference from endogenous biothiols, no background fluorescence, and good biocompatibility. With good cell permeability, GSSH-2TPE can monitor changes in Pb2+ levels and biodistribution and thus predict possible damage pathways. Such metal-peptide interaction-based sensing systems offer tailorable platforms for designing bioanalytical tools and show great potential for studying the cell biology of metal ions in living biosystems.


Assuntos
Materiais Biomiméticos/química , Chumbo/química , Peptídeos/química , Materiais Biomiméticos/metabolismo , Materiais Biomiméticos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Corantes Fluorescentes/química , Glutationa/química , Células HeLa , Humanos , Chumbo/análise , Limite de Detecção , Microscopia de Fluorescência , Estilbenos/química , Distribuição Tecidual
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