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1.
Sensors (Basel) ; 24(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38732893

RESUMO

An abnormal level of dopamine (DA), a kind of neurotransmitter, correlates with a series of diseases, including Parkinson's disease, Willis-Ekbom disease, attention deficit hyperactivity disorder, and schizophrenia. Hence, it is imperative to achieve a precise, rapid detection method in clinical medicine. In this study, we synthesized nanocomposite carbon aerogels (CAs) doped with iron and iron carbide, based on algae residue-derived biomass materials, using Fe(NO3)3 as the iron source. The modified glassy carbon electrode (GCE) for DA detection, denoted as CAs-Fe/GCE, was prepared through surface modification with this composite material. X-ray photoelectron spectroscopy and X-ray diffraction characterization confirmed the successful doping of iron into the as-prepared CAs. Additionally, the electrochemical behavior of DA on the modified electrode surface was investigated and the results demonstrate that the addition of the CAs-Fe promoted the electron transfer rate, thereby enhancing their sensing performance. The fabricated electrochemical DA biosensor exhibits an accurate detection of DA in the concentration within the range of 0.01~200 µM, with a detection limit of 0.0033 µM. Furthermore, the proposed biosensor is validated in real samples, showing its high applicability for the detection of DA in beverages.


Assuntos
Técnicas Biossensoriais , Carbono , Dopamina , Técnicas Eletroquímicas , Eletrodos , Ferro , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Dopamina/análise , Dopamina/química , Carbono/química , Ferro/química , Técnicas Eletroquímicas/métodos , Géis/química , Limite de Detecção , Espectroscopia Fotoeletrônica , Nanocompostos/química
2.
Sensors (Basel) ; 24(9)2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38733043

RESUMO

In this paper, a novel aptamer-modified nitrogen-doped graphene microelectrode (Apt-Au-N-RGOF) was fabricated and used to specifically identify and detect dopamine (DA). During the synthetic process, gold nanoparticles were loaded onto the active sites of nitrogen-doped graphene fibers. Then, aptamers were modified on the microelectrode depending on Au-S bonds to prepare Apt-Au-N-RGOF. The prepared microelectrode can specifically identify DA, avoiding interference with other molecules and improving its selectivity. Compared with the N-RGOF microelectrode, the Apt-Au-N-RGOF microelectrode exhibited higher sensitivity, a lower detection limit (0.5 µM), and a wider linear range (1~100 µM) and could be applied in electrochemical analysis fields.


Assuntos
Aptâmeros de Nucleotídeos , Dopamina , Técnicas Eletroquímicas , Ouro , Grafite , Nanopartículas Metálicas , Microeletrodos , Grafite/química , Dopamina/análise , Dopamina/química , Aptâmeros de Nucleotídeos/química , Ouro/química , Técnicas Eletroquímicas/métodos , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Limite de Detecção , Nitrogênio/química
3.
Luminescence ; 39(5): e4760, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38738510

RESUMO

The present communication reports on the synthesis of a novel methyl-pyridone azo fluorescent tag (MPAFT) were proven through 1H (NMR), FT-IR, UV-vis, and high-resolution mass spectrometry. The quantum chemical parameters of MPAFT were evaluated using density functional theory (DFT) analysis. It was further investigated for its latent fingerprint (LFPs) in various surfaces and anticounterfeiting applications. By exposing Level I-Level III, ridge features to UV light with a wavelength of 365 nm, a bioimaging investigation has also demonstrated the potential of MPAFT's emission behaviour. The cyclic voltammetry (CV) and linear sweep voltammetry (LSV) at MPAFT/MGCE (modified glassy carbon electrode) were used to explore the electrochemical sensitivity and reliable detection of dopamine (DA) in neutral PBS (pH 7) electrolyte solution, and the results show good sensitivity and detection. The lower detection limit for LSV was 0.81 µM under optimum conditions.


Assuntos
Dopamina , Técnicas Eletroquímicas , Corantes Fluorescentes , Pirazóis , Piridonas , Piridonas/química , Dopamina/análise , Dopamina/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Pirazóis/química , Humanos , Estrutura Molecular , Teoria da Densidade Funcional , Imagem Óptica , Processos Fotoquímicos
4.
Biosens Bioelectron ; 258: 116370, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38744115

RESUMO

Protein phosphorylation is a significant post-translational modification that plays a decisive role in the occurrence and development of diseases. However, the rapid and accurate identification of phosphoproteins remains challenging. Herein, a high-throughput sensor array has been constructed based on a magnetic bimetallic nanozyme (Fe3O4@ZNP@UiO-66) for the identification and discrimination of phosphoproteins. Attributing to the formation of Fe-Zr bimetallic dual active centers, the as-prepared Fe3O4@ZNP@UiO-66 exhibits enhanced peroxidase-mimicking catalytic activity, which promotes the electron transfer from Zr center to Fe(II)/Fe(III). The catalytic activity of Fe3O4@ZNP@UiO-66 can be selectively inhibited by phosphoproteins due to the strong interaction between phosphate groups and Zr centers, as well as the ultra-robust antifouling capability of zwitterionic dopamine nanoparticle (ZNP). Considering the diverse binding affinities between various proteins with the nanozyme, the catalytic activity of Fe3O4@ZNP@UiO-66 can be changed to various degree, leading to the different absorption responses at 420 nm in the hydrogen peroxide (H2O2) - 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) system. By simply extracting different absorbance intensities at various time points, a sensor array based on reaction kinetics for the discrimination of phosphoproteins from other proteins is constructed through linear discriminant analysis (LDA). Besides, the quantitative determination of phosphoproteins and identification of protein mixtures have been realized. Further, based on the differential level of phosphoproteins in cells, the differentiation of cancer cells from normal cells can also be implemented by utilizing the proposed sensor array, showing great potential in disease diagnosis.


Assuntos
Técnicas Biossensoriais , Peróxido de Hidrogênio , Neoplasias , Fosfoproteínas , Zircônio , Técnicas Biossensoriais/métodos , Humanos , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Peróxido de Hidrogênio/química , Zircônio/química , Peroxidase/química , Dopamina/química , Limite de Detecção , Materiais Biomiméticos/química , Catálise
5.
Langmuir ; 40(20): 10718-10725, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38728259

RESUMO

For accurate in vivo detection, nonspecific adsorption of biomacromolecules such as proteins and cells is a severe issue. The adsorption leads to electrode passivation, significantly compromising both the sensitivity and precision of sensing. Meanwhile, common antibiofouling modifications, such as polymer coatings, still grapple with issues related to biocompatibility, electrode passivation, and miniaturization. Herein, we propose a composite antibiofouling coating strategy based on zwitterionic metal-organic frameworks (Z-MOFs) and a combination of acrylamide hydrogels. On a well-designed TiO2/Z-MOF/hydrogel photoelectrode, we achieve highly sensitive and selective detection of dopamine in complex biological environments. The hydrogel's three-dimensional porous structure combined with unique microporous architecture of Z-MOF ensures effective sieving of interfering macromolecules while preserving efficient small molecules and electron transport. This innovative approach paves the way for constructing miniature, in vivo antibiofouling sensors for molecule monitoring in living organisms with complicated chemical environments.


Assuntos
Técnicas Biossensoriais , Dopamina , Hidrogéis , Titânio , Hidrogéis/química , Dopamina/análise , Dopamina/química , Técnicas Biossensoriais/métodos , Titânio/química , Incrustação Biológica/prevenção & controle , Técnicas Eletroquímicas/métodos , Processos Fotoquímicos , Estruturas Metalorgânicas/química , Materiais Biocompatíveis/química , Eletrodos
6.
Carbohydr Polym ; 337: 122146, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710570

RESUMO

Diabetic wounds remain a global challenge due to disordered wound healing led by inflammation, infection, oxidative stress, and delayed proliferation. Therefore, an ideal wound dressing for diabetic wounds not only needs tissue adhesiveness, injectability, and self-healing properties but also needs a full regulation of the microenvironment. In this work, adhesive wound dressings (HA-DA/PRP) with injectability were fabricated by combining platelet rich plasma (PRP) and dopamine-modified-hyaluronic acid (HA-DA). The engineered wound dressings exhibited tissue adhesiveness, rapid self-healing, and shape adaptability, thereby enhancing stability and adaptability to irregular wounds. The in vitro experiments demonstrated that HA-DA/PRP adhesives significantly promoted fibroblast proliferation and migration, attributed to the loaded PRP. The adhesives showed antibacterial properties against both gram-positive and negative bacteria. Moreover, in vitro experiments confirmed that HA-DA/PRP adhesives effectively mitigated oxidative stress and inflammation. Finally, HA-DA/PRP accelerated the healing of diabetic wounds by inhibiting bacterial growth, promoting granulation tissue regeneration, accelerating neovascularization, facilitating collagen deposition, and modulating inflammation through inducing M1 to M2 polarization, in an in vivo model of infected diabetic wounds. Overall, HA-DA/PRP adhesives with the ability to comprehensively regulate the microenvironment in diabetic wounds may provide a novel approach to expedite the diabetic wounds healing in clinic.


Assuntos
Antibacterianos , Diabetes Mellitus Experimental , Ácido Hialurônico , Hidrogéis , Plasma Rico em Plaquetas , Cicatrização , Ácido Hialurônico/química , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Plasma Rico em Plaquetas/química , Antibacterianos/farmacologia , Antibacterianos/química , Diabetes Mellitus Experimental/tratamento farmacológico , Camundongos , Ratos , Bandagens , Masculino , Proliferação de Células/efeitos dos fármacos , Humanos , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacos , Dopamina/química , Fibroblastos/efeitos dos fármacos , Adesivos/química , Adesivos/farmacologia
7.
J Inorg Biochem ; 256: 112548, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38593610

RESUMO

Neuromelanin (NM) plays a well-established role in neurological disorders pathogenesis; the mechanism of action is still discussed and the investigations in this field are limited by NM's complex and heterogeneous composition, insolubility, and low availability from human brains. An alternative can be offered by synthetic NM obtained from dopamine (DA) oxidative polymerization; however, a deep knowledge of the influence of both physicochemical parameters (T, pH, ionic strength) and other compounds in the reaction media (buffer, metal ions, other catecholamines) on DA oxidation process and, consequently, on synthetic NM features is mandatory to develop reliable NM preparation methodologies. To partially fulfill this aim, the present work focuses on defining the role of temperature, buffer and metal ions on both DA oxidation rate and DA oligomer size. DA oxidation in the specific conditions is monitored by UV-Vis spectroscopy and Principal Component Analysis (PCA) is run either on the raw spectra to model the background absorption increase, related to small DA oligomers formation, or on their first derivative to rationalize DA consumption. After having studied three case studies, 3-Way PCA is applied to directly evaluate the effect of temperature and buffer type on DA oxidation in the presence of different metal ions. Despite the proof-of-concept nature of the work and the number of compounds still to be included in the investigation, the preliminary results and the possibility to further expand the chemometric approach represent an interesting contribution to the field of in vitro simulation of NM synthesis.


Assuntos
Dopamina , Melaninas , Oxirredução , Polimerização , Análise de Componente Principal , Dopamina/metabolismo , Dopamina/química , Melaninas/química , Melaninas/metabolismo , Melaninas/biossíntese , Temperatura , Humanos , Soluções Tampão , Metais/química , Concentração de Íons de Hidrogênio
8.
Anal Chem ; 96(15): 6037-6044, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38560885

RESUMO

Dopamine (DA), an essential neurotransmitter, is closely associated with various neurological disorders, whose real-time dynamic monitoring is significant for evaluating the physiological activities of neurons. Electrochemical sensing methods are commonly used to determine DA, but they mostly rely on the redox reaction of its o-phenolic hydroxyl group, which makes it difficult to distinguish it from substances with this group. Here, we design a biomimetic nanozyme inspired by the coordination structure of the copper-based active site of dopamine ß-hydroxylase, which was successfully synthesized via a urea-mediated MOF pyrolysis reconstruction strategy. Experimental studies and theoretical calculations revealed that the nanozyme with Cu-N3 coordination could hydroxylate the carbon atom of the DA ß-site at a suitable potential and that the active sites of this Cu-N3 structure have the lowest binding energy for the DA ß-site. With this property, the new oxidation peak achieves the specific detection of DA rather than the traditional electrochemical signal of o-phenol hydroxyl redox, which would effectively differentiate it from neurotransmitters, such as norepinephrine and epinephrine. The sensor exhibited good monitoring capability in DA concentrations from 0.05 to 16.7 µM, and its limit of detection was 0.03 µM. Finally, the sensor enables the monitoring of DA released from living cells and can be used to quantitatively analyze the effect of polystyrene microplastics on the amount of DA released. The research provides a method for highly specific monitoring of DA and technical support for initial screening for neurocytotoxicity of pollutants.


Assuntos
Dopamina , Oxigenases de Função Mista , Dopamina/química , Fenol , Biomimética , Cobre , Plásticos , Pirólise , Eletrodos , Neurotransmissores , Técnicas Eletroquímicas/métodos
9.
J Chromatogr A ; 1724: 464910, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38657316

RESUMO

A simplified approach for preparation of sandwich type molecularly imprinted polymers (PPDA-MIPs) is proposed for simultaneously identify Low-density lipoprotein (LDL) and dispose "bad cholesterol". Porous polydopamine nanosphere (PPDA) is applied as a matrix for immobilization of LDL, and the imprinted layer is formed by dopamine acting as a functional monomer. Since imprinted cavities exhibit shape memory effects in terms of recognizing selectivity, the PPDA-MIPs exhibit excellent selectivity toward LDL and a substantial binding capacity of 550.3 µg mg-1. Meanwhile, six adsorption/desorption cycles later, the adsorption efficiency of 83.09 % is still achieved, indicating the adequate stability and reusability of PPDA-MIPs. Additionally, over 80 % of cholesterol is recovered, indicating the completeness of "bad cholesterol" removal in LDL. Lastly, as demonstrated by gel electrophoresis, PPDA-MIPs performed satisfactory behavior for the removal of LDL from the goat serum sample.


Assuntos
Colesterol , Indóis , Lipoproteínas LDL , Polímeros Molecularmente Impressos , Polímeros , Lipoproteínas LDL/sangue , Lipoproteínas LDL/química , Lipoproteínas LDL/isolamento & purificação , Adsorção , Polímeros/química , Colesterol/sangue , Colesterol/química , Indóis/química , Animais , Polímeros Molecularmente Impressos/química , Dopamina/sangue , Dopamina/química , Dopamina/isolamento & purificação , Dopamina/análise , Impressão Molecular/métodos , Cabras , Nanosferas/química
10.
J Org Chem ; 89(9): 5977-5987, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38557022

RESUMO

Mellpaladines A-C (1-3) and dopargimine (4) are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine (5), three additional mellpaladines D-F (6-8), and serotodopalgimine (9), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine (10). The structures of these compounds were determined based on spectrometric and spectroscopic analyses. Compound 4 and its congeners dopargine (11), nordopargimine (15), and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)ethan-1-amine (16) were synthetically prepared for biological evaluations. The biological activities of all isolated compounds were evaluated in comparison with those of 1-4 using a mouse behavioral assay upon intracerebroventricular injection, revealing key functional groups in the dopargimines and mellpaladines for in vivo behavioral toxicity. Interestingly, these alkaloids also emerged during a screen of our marine natural product library aimed at identifying antiviral activities against dengue virus, SARS-CoV-2, and vesicular stomatitis Indiana virus (VSV) pseudotyped with Ebola virus glycoprotein (VSV-ZGP).


Assuntos
Alcaloides , Dopamina , Urocordados , Animais , Alcaloides/química , Alcaloides/farmacologia , Alcaloides/isolamento & purificação , Alcaloides/síntese química , Urocordados/química , Camundongos , Dopamina/química , Dopamina/farmacologia , Estrutura Molecular , Guanidina/química , Guanidina/farmacologia , Antivirais/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/síntese química , Guanidinas/química , Guanidinas/farmacologia , Guanidinas/isolamento & purificação , SARS-CoV-2/efeitos dos fármacos , Humanos
11.
Talanta ; 274: 126003, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38569374

RESUMO

Antibiotics in aquatic environments raise health concerns. Therefore, the rapid, on-site, and accurate detection of antibiotic residues is crucial for protecting the environment and human health. Herein, a dumbbell-shaped iron (Fe3+)-dopamine coordination nanozyme (Fe-DCzyme) was developed via an iron-driven self-assembly strategy. It exhibited excellent peroxidase-like activity, which can be quenched by adding l-cysteine to prevent Fe3+/Fe2+ electron transfer but restored by adding norfloxacin. Given the 'On-Off-On' effect of peroxidase-like activity, Fe-DCzyme was used as a colourimetric sensor for norfloxacin detection, and showed a wide linear range from 0.05 to 6.00 µM (R2 = 0.9950) and LOD of 27.0 nM. A portable smartphone-assisted detection platform using Fe-DCzyme was also designed to convert norfloxacin-induced color changes into RGB values as well as to realise the rapid, on-site and quantitative detection of norfloxacin. A good linear relation (0.10-6.00 µM) and high sensitivity (LOD = 79.3 nM) were achieved for the smartphone-assisted Fe-DCzyme detection platform. Its application was verified using norfloxacin spiking methods with satisfactory recoveries (92.66%-119.65%). Therefore, the portable smartphone-assisted Fe-DCzyme detection platform with low cost and easy operation can be used for the rapid, on-site and visual quantitative detection of antibiotic residues in water samples.


Assuntos
Colorimetria , Dopamina , Ferro , Norfloxacino , Smartphone , Norfloxacino/análise , Norfloxacino/química , Ferro/química , Dopamina/análise , Dopamina/química , Colorimetria/métodos , Antibacterianos/análise , Antibacterianos/química , Poluentes Químicos da Água/análise , Limite de Detecção , Nanoestruturas/química
12.
Molecules ; 29(8)2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38675592

RESUMO

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, primarily associated with dopaminergic neuron depletion in the Substantia Nigra. Current treatment focuses on compensating for dopamine (DA) deficiency, but the blood-brain barrier (BBB) poses challenges for effective drug delivery. Using differentiated SH-SY5Y cells, we investigated the co-administration of DA and the antioxidant Grape Seed Extract (GSE) to study the cytobiocompability, the cytoprotection against the neurotoxin Rotenone, and their antioxidant effects. For this purpose, two solid lipid nanoparticle (SLN) formulations, DA-co-GSE-SLNs and GSE-ads-DA-SLNs, were synthesized. Such SLNs showed mean particle sizes in the range of 187-297 nm, zeta potential values in the range of -4.1--9.7 mV, and DA association efficiencies ranging from 35 to 82%, according to the formulation examined. The results showed that DA/GSE-SLNs did not alter cell viability and had a cytoprotective effect against Rotenone-induced toxicity and oxidative stress. In addition, this study also focused on the evaluation of Alpha-synuclein (aS) levels; SLNs showed the potential to modulate the Rotenone-mediated increase in aS levels. In conclusion, our study investigated the potential of SLNs as a delivery system for addressing PD, also representing a promising approach for enhanced delivery of pharmaceutical and antioxidant molecules across the BBB.


Assuntos
Sobrevivência Celular , Dopamina , Extrato de Sementes de Uva , Nanopartículas , Doença de Parkinson , Rotenona , alfa-Sinucleína , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Dopamina/química , Dopamina/metabolismo , Nanopartículas/química , Extrato de Sementes de Uva/química , Extrato de Sementes de Uva/farmacologia , Rotenona/farmacologia , Linhagem Celular Tumoral , alfa-Sinucleína/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Estresse Oxidativo/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Tamanho da Partícula , Lipossomos/química , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo
13.
Biosens Bioelectron ; 257: 116332, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677016

RESUMO

In situ detection of dopamine (DA) at single-cell level is critical for exploring neurotransmitter-related biological processes and diseases. However, the low content of DA and a variety of distractors with similar oxidation potentials as DA in cells brought great challenges. Here, a sensitive and specific electrochemical nanosensor was proposed for in situ detection of DA in single living cells based on nanodiamond (ND) and molecularly imprinted polymer (MIP)-functionalized carbon fiber nanoelectrode (ND/MIP/CFNE). Due to its excellent electrocatalytic property, ND was modified to the surface of CFNE based on amide bonding. Compared with bare CFNE, ND-modified CFNE can enhance oxidation currents of DA by about 4-fold, improving signal-to-noise ratio and detection sensitivity. MIP was further electropolymerized on the surface of nanoelectrodes to achieve specific capture and recognition of DA, which could avoid the interference of complex matrix and analogs in cells. Taking advantage of the precise positioning capability of a single-cell analyzer and micromanipulator, ND/MIP/CFNE could be precisely inserted into different locations of single cells and monitor oxidation signal of DA. The concentration of DA in the cytoplasm of single pheochromocytoma (PC12) cell was measured to be about 0.4 µM, providing a sensitive and powerful method for single-cell detection. Furthermore, the nanoelectrodes can monitor the fluctuation of intracellular DA under drug stimulation, providing new ideas and methods for new drug development and efficacy evaluation.


Assuntos
Técnicas Biossensoriais , Dopamina , Técnicas Eletroquímicas , Polímeros Molecularmente Impressos , Análise de Célula Única , Dopamina/análise , Dopamina/química , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Células PC12 , Técnicas Eletroquímicas/métodos , Polímeros Molecularmente Impressos/química , Animais , Ratos , Nanodiamantes/química , Eletrodos , Fibra de Carbono/química , Impressão Molecular/métodos , Limite de Detecção , Polímeros/química
14.
Nature ; 629(8010): 235-243, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38499039

RESUMO

Biogenic monoamines-vital transmitters orchestrating neurological, endocrinal and immunological functions1-5-are stored in secretory vesicles by vesicular monoamine transporters (VMATs) for controlled quantal release6,7. Harnessing proton antiport, VMATs enrich monoamines around 10,000-fold and sequester neurotoxicants to protect neurons8-10. VMATs are targeted by an arsenal of therapeutic drugs and imaging agents to treat and monitor neurodegenerative disorders, hypertension and drug addiction1,8,11-16. However, the structural mechanisms underlying these actions remain unclear. Here we report eight cryo-electron microscopy structures of human VMAT1 in unbound form and in complex with four monoamines (dopamine, noradrenaline, serotonin and histamine), the Parkinsonism-inducing MPP+, the psychostimulant amphetamine and the antihypertensive drug reserpine. Reserpine binding captures a cytoplasmic-open conformation, whereas the other structures show a lumenal-open conformation stabilized by extensive gating interactions. The favoured transition to this lumenal-open state contributes to monoamine accumulation, while protonation facilitates the cytoplasmic-open transition and concurrently prevents monoamine binding to avoid unintended depletion. Monoamines and neurotoxicants share a binding pocket that possesses polar sites for specificity and a wrist-and-fist shape for versatility. Variations in this pocket explain substrate preferences across the SLC18 family. Overall, these structural insights and supporting functional studies elucidate the mechanism of vesicular monoamine transport and provide the basis to develop therapeutics for neurodegenerative diseases and substance abuse.


Assuntos
Monoaminas Biogênicas , Interações Medicamentosas , Proteínas Vesiculares de Transporte de Monoamina , Humanos , 1-Metil-4-fenilpiridínio/química , 1-Metil-4-fenilpiridínio/metabolismo , 1-Metil-4-fenilpiridínio/farmacologia , Anfetamina/química , Anfetamina/farmacologia , Anfetamina/metabolismo , Sítios de Ligação , Monoaminas Biogênicas/química , Monoaminas Biogênicas/metabolismo , Microscopia Crioeletrônica , Dopamina/química , Dopamina/metabolismo , Modelos Moleculares , Norepinefrina/química , Norepinefrina/metabolismo , Ligação Proteica , Prótons , Reserpina/farmacologia , Reserpina/química , Reserpina/metabolismo , Serotonina/química , Serotonina/metabolismo , Especificidade por Substrato , Proteínas Vesiculares de Transporte de Monoamina/química , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Proteínas Vesiculares de Transporte de Monoamina/ultraestrutura
15.
Anal Chim Acta ; 1298: 342415, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38462342

RESUMO

BACKGROUND: Tyramine is an important index of food freshness degree, and tyrosinase that can specifically oxidized monophenolamine to catecholamine plays a crucial part in the occurrence and development of melanin-related skin diseases. Therefore, it is crucial to develop sensitive and efficient methods for the detection of tyramine and tyrosinase. RESULTS: In this work, encouraged by tyrosinase-triggered specific oxidation of tyramine to dopamine and the unique fluorescent reaction between dopamine and amino silane, we have developed a one-step synthetic strategy of silicon containing nanoparticles (Si CNPs) for "turn-on" detection of tyramine and tyrosinase. The Si CNPs formed with thoroughly studied mechanism exhibit uniform structure and robust yellow-green fluorescence. The low detection limits for tyramine (1.87 µM) and tyrosinase (0.0029 U/mL) demonstrate admirable sensitivity outstripping most methods. The proposed assay achieves satisfactory results in the determination of tyramine and tyrosinase activity in real samples. Furthermore, we leverage this new fluorescent assay to enable the fabrication of an "AND" Boolean logic gate. SIGNIFICANCE: The entire process can be completed at easily available temperature and pressure with rapid response, convenient operation and visual observation. This fluorescent assay featured with excellent sensitivity, selectivity and stability has considerable prospects in the application of biosensors and disease diagnosis.


Assuntos
Monofenol Mono-Oxigenase , Nanopartículas , Monofenol Mono-Oxigenase/química , Dopamina/química , Silício , Tiramina , Nanopartículas/química
16.
J Phys Chem B ; 128(12): 2885-2896, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38488148

RESUMO

Polydopamine (pDA) is a valuable material with wide-ranging potential applications. However, the complex and debated nature of dopamine polymerization complicates our understanding. Specifically, the impact of foreign substances, especially proteins, on pDA formation adds an additional layer of subtlety and complexity. This study delves into specific surface features of proteins that predominantly shape their impact on dopamine polymerization. Notably, the biotin-binding site emerges as a critical region responsible for the pronounced inhibitory effect of avidin and neutravidin on the dopamine polymerization process. The binding of biotin successfully mitigates these inhibitory effects. Moreover, several nucleases demonstrated a significant hindrance to pDA formation, with their impact substantially alleviated through the introduction of DNA. It is speculated that hydrogen bonding, electrostatic, cation-π, and/or hydrophobic interactions may underlie the binding between protein surfaces and diverse oligomeric intermediates formed by the oxidation products of dopamine. Additionally, we observed a noteworthy blocking effect on the dopamine polymerization reaction induced by erythropoietin (EPO), a glycoprotein hormone known for its role in stimulating red blood cell production and demonstrating neuroprotective effects. The inhibitory influence of EPO persisted even after deglycosylation. These findings not only advance our comprehension of the mechanisms underlying dopamine polymerization but also provide strategic insights for manipulating the reaction to tailor desired biomaterials.


Assuntos
Biotina , Dopamina , Dopamina/química , Polimerização , Materiais Biocompatíveis
17.
ACS Sens ; 9(4): 1785-1798, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38384144

RESUMO

Real-time sensing of dopamine is essential for understanding its physiological function and clarifying the pathophysiological mechanism of diseases caused by impaired dopamine systems. However, severe fouling from nonspecific protein adsorption, for a long time, limited conventional neural recording electrodes concerning recording stability. This study reported a high-antifouling nanocrystalline boron-doped diamond microsensor grown on a carbon fiber substrate. The antifouling properties of this diamond sensor were strongly related to the grain size (i.e., nanocrystalline and microcrystalline) and surface terminations (i.e., oxygen and hydrogen terminals). Experimental observations and molecular dynamics calculations demonstrated that the oxygen-terminated nanocrystalline boron-doped diamond microsensor exhibited enhanced antifouling characteristics against protein adsorption, which was attributed to the formation of a strong hydration layer as a physical and energetic barrier that prevents protein adsorption on the surface. This finally allowed for in vivo monitoring of dopamine in rat brains upon potassium chloride stimulation, thus presenting a potential solution for the design of next-generation antifouling neural recording sensors. Experimental observations and molecular dynamics calculations demonstrated that the oxygen-terminated nanocrystalline boron-doped diamond (O-NCBDD) microsensor exhibited ultrahydrophilic properties with a contact angle of 4.9°, which was prone to forming a strong hydration layer as a physical and energetic barrier to withstand the adsorption of proteins. The proposed O-NCBDD microsensor exhibited a high detection sensitivity of 5.14 µA µM-1 cm-2 and a low detection limit of 25.7 nM. This finally allowed for in vivo monitoring of dopamine with an average concentration of 1.3 µM in rat brains upon 2 µL of potassium chloride stimulation, thus presenting a potential solution for the design of next-generation antifouling neural recording sensors.


Assuntos
Diamante , Dopamina , Dopamina/análise , Dopamina/química , Animais , Diamante/química , Interações Hidrofóbicas e Hidrofílicas , Ratos , Incrustação Biológica/prevenção & controle , Boro/química , Neurotransmissores/análise , Técnicas Biossensoriais/métodos , Adsorção , Simulação de Dinâmica Molecular , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Masculino , Nanopartículas/química
18.
Molecules ; 29(3)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38338487

RESUMO

In this paper, a highly conductive alkali-activated graphitized carbon (a-GC) was prepared using tilapia fish scales as precursors through enzymolysis, activation and pyrolytic carbonization methods. The prepared a-GC was modified on the surface of a screen-printed carbon electrode to construct a flexible portable electrochemical sensing platform, which was applied to the differential pulse voltametric detection of dopamine (DA) using a U-disk electrochemical workstation combined with a smart phone and Bluetooth. The prepared a-GC possesses good electrical conductivity, a large specific surface area and abundant active sites, which are beneficial for the electrooxidation of DA molecules and result in excellent sensitivity and high selectivity for DA analysis. Under the optimal conditions, the oxidation peak current of DA increased gradually, with its concentrations in the range from 1.0 µmol/L to 1000.0 µmol/L, with the detection limit as low as 0.25 µmol/L (3S/N). The proposed sensor was further applied to the determination of DA in human sweat samples, with satisfactory results, which provided an opportunity for developing noninvasive early diagnosis and nursing equipment.


Assuntos
Carbono , Dopamina , Animais , Humanos , Dopamina/química , Carbono/química , Técnicas Eletroquímicas/métodos , Reprodutibilidade dos Testes , Carvão Vegetal , Eletrodos
19.
Biosensors (Basel) ; 14(2)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38392021

RESUMO

Single-entity electrochemistry, which employs electrolysis during the collision of single particles on ultramicroelectrodes, has witnessed significant advancements in recent years, enabling the observation and characterization of individual particles. Information on a single aqueous droplet (e.g., size) can also be studied based on the redox species contained therein. Dopamine, a redox-active neurotransmitter, is usually present in intracellular vesicles. Similarly, in the current study, the electrochemical properties of neurotransmitters in submicron droplets were investigated. Because dopamine oxidation is accompanied by proton transfer, unique electrochemical properties of dopamine were observed in the droplet. We also investigated the electrochemical properties of the adsorbed droplets containing DA and the detection of oxidized dopamine by the recollision phenomenon.


Assuntos
Dopamina , Água , Dopamina/química , Eletroquímica , Oxirredução
20.
Soft Matter ; 20(9): 2017-2023, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38334445

RESUMO

Surgical adhesives play a crucial role in tissue integration and repair, yet their application in wet conditions has been severely limited by inadequate adhesive strength and subpar biocompatibility. Furthermore, tissue adhesives have rarely been reported in cartilage tissue repair. In this study, a three-armed dopamine-modified hyaluronic acid derivative adhesive was prepared to function as a bio-inspired adhesive in moist environments. To meet the clinical requirements for cartilage tissue adhesion, we studied its chemical structure, including microscopic morphology, adhesion properties with materials and tissues, in vivo degradation rules, and biological evaluation. The OGMHA8-DOPA adhesive with the optimal aldehyde substitution degree and dopamine-grafting rate was determined by analyzing the experimental conditions. SEM results revealed that the cartilage tissue adhered to a porous interconnected structure. The excellent biocompatibility of the material not only facilitated chondrocyte adhesion but also supported their proliferation on its surface. Animal experiments have demonstrated that this material has no observable inflammatory response or incidence of fibrous capsule formation. The degradation timeline of the material extends beyond the duration of two weeks. The dopamine-modified adhesive exhibited a tight interfacial binding force between the biomaterial and cartilage tissue and excellent biocompatibility in watery tissue, revealing its potential for application in cartilage tissue repair and minimally invasive surgery.


Assuntos
Adesivos , Materiais Biocompatíveis , Animais , Materiais Biocompatíveis/farmacologia , Adesivos/química , Dopamina/química , Cartilagem , Condrócitos
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