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1.
Anal Chim Acta ; 1188: 339181, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34794568

RESUMO

In this work, MnO2 nanoflower (NF), as novel and more effective co-reaction accelerator, was applied to construct a new ternary electrochemiluminescence (ECL) system of Ru complex/tripropylamine (TPrA)/MnO2 NF. Compared with the classic Ru complex/TPrA binary ECL system, the reaction efficiency of co-reactant TPrA in the new ternary ECL system was obviously enhanced, leading to the significantly improved ECL signal by accelerating the dissociation of co-reactants into more active radicals. Then, an ECL biosensor was fabricated based on the proposed ternary ECL system, realizing the sensitive determination of glutathione (GSH). In order to realize the efficient nucleic acid amplification, a certain amount of GSH was firstly converted to a large number of intermediate DNA in assistance of Hg2+, which acted as walker could walk along with the DNA triplex immobilized on the electrode and cut off the DNA strand (S2) labeled with ferrocene (Fc). Owing to the fact that Fc possessed obvious quenching effect to the ECL of Ru complex labeled on the other side of S2, the ECL signal recovered significantly. Thus, the proposed ECL biosensor achieved the sensitive determination of GSH, and the detection limit was 50 nM.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Glutationa , Medições Luminescentes , Compostos de Manganês , Óxidos , Propilaminas
2.
Molecules ; 26(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34641270

RESUMO

The conjugation of biomolecules to magnetic nanoparticles has emerged as promising approach in biomedicine as the treatment of several diseases, such as cancer. In this study, conjugation of bioactive peptide fractions from germinated soybeans to magnetite nanoparticles was achieved. Different fractions of germinated soybean peptides (>10 kDa and 5-10 kDa) were for the first time conjugated to previously coated magnetite nanoparticles (with 3-aminopropyltriethoxysilane (APTES) and sodium citrate) by the Ugi four-component reaction. The crystallinity of the nanoparticles was corroborated by X-ray diffraction, while the particle size was determined by scanning transmission electron microscopy. The analyses were carried out using infrared and ultraviolet-visible spectroscopy, dynamic light scattering, and thermogravimetry, which confirmed the coating and functionalization of the magnetite nanoparticles and conjugation of different peptide fractions on their surfaces. The antioxidant activity of the conjugates was determined by the reducing power and hydroxyl radical scavenging activity. The nanoparticles synthesized represent promising materials, as they have found applications in bionanotechnology for enhanced treatment of diseases, such as cancer, due to a higher antioxidant capacity than that of fractions without conjugation. The highest antioxidant capacity was observed for a >10 kDa peptide fraction conjugated to the magnetite nanoparticles coated with APTES.


Assuntos
Antioxidantes/farmacologia , Nanopartículas de Magnetita/química , Peptídeos/farmacologia , Soja/química , Antioxidantes/química , Sequestradores de Radicais Livres/química , Germinação , Tamanho da Partícula , Peptídeos/química , Propilaminas/química , Silanos/química , Citrato de Sódio/química , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Difração de Raios X
3.
Molecules ; 26(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34641509

RESUMO

A dual recognition system with a fluorescence quenching of quantum dots (QDs) and specific recognition of molecularly imprinted polymer (MIP) for the detection of chloramphenicol (CAP) was constructed. MIP@SiO2@QDs was prepared by reverse microemulsion method with 3-aminopropyltriethoxysilane (APTS), tetraethyl orthosilicate (TEOS) and QDs being used as the functional monomer, cross-linker and signal sources, respectively. MIP can specifically recognize CAP, and the fluorescence of QDs can be quenched by CAP due to the photo-induced electron transfer reaction between CAP and QDs. Thus, a method for the trace detection of CAP based on MIP@SiO2@QDs fluorescence quenching was established. The fluorescence quenching efficiency of MIP@SiO2@QDs displayed a desirable linear response to the concentration of CAP in the range of 1.00~4.00 × 102 µmol × L-1, and the limit of detection was 0.35 µmol × L-1 (3σ, n = 9). Importantly, MIP@SiO2@QDs presented good detection selectivity owing to specific recognition for CAP, and was successfully applied to quantify CAP in lake water with the recovery ranging 102.0~104.0%, suggesting this method has the promising potential for the on-site detection of CAP in environmental waters.


Assuntos
Cloranfenicol/análise , Fluorometria/métodos , Pontos Quânticos/química , Compostos de Cádmio/química , Fluorescência , Concentração de Íons de Hidrogênio , Lagos/análise , Limite de Detecção , Microscopia Eletrônica de Transmissão , Impressão Molecular , Propilaminas/química , Sensibilidade e Especificidade , Silanos/química , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier , Telúrio/química , Poluentes Químicos da Água/análise
4.
FASEB J ; 35(10): e21874, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34486176

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations of PKD1 or PKD2 genes, is characterized by development and growth of cysts causing progressive kidney enlargement. Reduced resting cytosolic calcium and increased cAMP levels associated with the tonic action of vasopressin are two central biochemical defects in ADPKD. Here we show that co-targeting two GPCRs, the vasopressin V2 receptor (V2R) and the calcium sensing receptor, using the novel V2R antagonist lixivaptan in combination with the calcimimetic R-568, reduced cyst progression in two animal models of human PKD. Lixivaptan is expected to have a safer liver profile compared to tolvaptan, the only drug approved to delay PKD progression, based on computational model results and initial clinical evidence. PCK rat and Pkd1RC/RC mouse littermates were fed without or with lixivaptan (0.5%) and R-568 (0.025% for rats and 0.04% for mice), alone or in combination, for 7 (rats) or 13 (mice) weeks. In PCK rats, the combined treatment strongly decreased kidney weight, cyst and fibrosis volumes by 20%, 49%, and 73%, respectively, compared to untreated animals. In Pkd1RC/RC mice, the same parameters were reduced by 20%, 56%, and 69%, respectively. In both cases the combined treatment appeared nominally more effective than the individual drugs used alone. These data point to an intriguing new application for two existing drugs in PKD treatment. The potential for synergy between these two compounds suggested in these animal studies, if confirmed in appropriate clinical investigations, would represent a welcome advancement in the treatment of ADPKD.


Assuntos
Benzamidas/farmacologia , Fenetilaminas/farmacologia , Rim Policístico Autossômico Dominante/tratamento farmacológico , Propilaminas/farmacologia , Pirróis/farmacologia , Receptores de Detecção de Cálcio/antagonistas & inibidores , Receptores de Vasopressinas/química , Animais , AMP Cíclico , Quimioterapia Combinada , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Rim Policístico Autossômico Dominante/metabolismo , Rim Policístico Autossômico Dominante/patologia , Ratos , Ratos Sprague-Dawley
5.
Acta Vet Hung ; 69(3): 298-302, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34520389

RESUMO

This paper presents a clinical case report of a golden eagle (Aquila chrysaetos) with foreign bodies (stones) in its proventriculus. The case deals with the identification, management and removal of foreign objects identified in the gastrointestinal tract. A surgical removal by proventriculotomy under general anaesthesia was attempted. The surgery and the recovery were uneventful, and the follow-up after six months revealed no complications. To the best of our knowledge, there are no other reports of successful foreign body removal by proventriculotomy in the golden eagle.


Assuntos
Doenças das Aves , Águias , Corpos Estranhos , Animais , Corpos Estranhos/cirurgia , Corpos Estranhos/veterinária , Propilaminas , Proventrículo , Sulfetos
6.
ACS Chem Biol ; 16(9): 1615-1621, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34403242

RESUMO

Ubiquitin activity-based probes have proven invaluable in elucidating structural mechanisms in the ubiquitin system by stabilizing transient macromolecular complexes of deubiquitinases, ubiquitin-activating enzymes, and the assemblies of ubiquitin-conjugating enzymes with ubiquitin ligases of the RING-Between-RING and RING-Cysteine-Relay families. Here, we demonstrate that an activity-based probe, ubiquitin-propargylamine, allows for the preparative reconstitution and structural analysis of the interactions between ubiquitin and certain HECT ligases. We present a crystal structure of the ubiquitin-linked HECT domain of HUWE1 that defines a catalytically critical conformation of the C-terminal tail of the ligase for the transfer of ubiquitin to an acceptor protein. Moreover, we observe that ubiquitin-propargylamine displays selectivity among HECT domains, thus corroborating the notion that activity-based probes may provide entry points for the development of specific, active site-directed inhibitors and reporters of HECT ligase activities.


Assuntos
Enzimas de Conjugação de Ubiquitina/química , Ubiquitina-Proteína Ligases/química , Ubiquitina/química , Sequência de Aminoácidos , Catálise , Domínio Catalítico , Cisteína/química , Humanos , Modelos Moleculares , Pargilina/análogos & derivados , Pargilina/química , Propilaminas/química , Conformação Proteica , Relação Estrutura-Atividade , Especificidade por Substrato , Ubiquitinação
7.
J Biol Chem ; 297(2): 100940, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34237302

RESUMO

The severe acute respiratory syndrome coronavirus 2 envelope protein (S2-E) is a conserved membrane protein that is important for coronavirus (CoV) assembly and budding. Here, we describe the recombinant expression and purification of S2-E in amphipol-class amphipathic polymer solutions, which solubilize and stabilize membrane proteins, but do not disrupt membranes. We found that amphipol delivery of S2-E to preformed planar bilayers results in spontaneous membrane integration and formation of viroporin cation channels. Amphipol delivery of the S2-E protein to human cells results in plasma membrane integration, followed by retrograde trafficking to the trans-Golgi network and accumulation in swollen perinuclear lysosomal-associated membrane protein 1-positive vesicles, likely lysosomes. CoV envelope proteins have previously been proposed to manipulate the luminal pH of the trans-Golgi network, which serves as an accumulation station for progeny CoV particles prior to cellular egress via lysosomes. Delivery of S2-E to cells will enable chemical biological approaches for future studies of severe acute respiratory syndrome coronavirus 2 pathogenesis and possibly even development of "Trojan horse" antiviral therapies. Finally, this work also establishes a paradigm for amphipol-mediated delivery of membrane proteins to cells.


Assuntos
Membrana Celular/efeitos dos fármacos , Proteínas do Envelope de Coronavírus/metabolismo , Polímeros/farmacologia , Propilaminas/farmacologia , Tensoativos/farmacologia , Rede trans-Golgi/metabolismo , Membrana Celular/metabolismo , Proteínas do Envelope de Coronavírus/genética , Células HeLa , Humanos , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Lisossomos/metabolismo , Polímeros/química , Propilaminas/química , Transporte Proteico , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Tensoativos/química
8.
Biosensors (Basel) ; 11(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209744

RESUMO

Bioelectrodes mediated by metal oxide nanoparticles have facilitated the development of new sensors in medical diagnosis. High-purity TiO2 nanoparticles (NPs) were synthesized through thermal plasma and deposited directly on an interdigitated electrode. The surface of the TiO2-deposited electrode was activated with (3-aminopropyl) triethoxysilane (APTES) followed by fixing the single-stranded probe deoxyribonucleic acid (DNA) to fabricate the DNA biosensor. The structural properties of the deposited TiO2 nanoparticles were analyzed using a transmission electron microscope (TEM), X-ray diffraction (XRD), and a dynamic light scattering (DLS) system. The chemical composition and structural properties of the TiO2 nanoparticle layer and the fixed layer were analyzed by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). E. coli O157:H7, a well-known pernicious pathogenic bacterial species, was detected as a target DNA of the prepared DNA biosensor, and the characteristics of DNA detection were determined by the current change using a picoammeter. The degree of binding between the probe DNA and the target DNA was converted into an electrical signal using the picoammeter method to quantitatively analyze the concentration of the target DNA. With the specificity experiment, it was confirmed that the biosensor was able to discriminate between nucleotides with mismatched, non-complementary, or complementary sequences.


Assuntos
Técnicas Biossensoriais , DNA/análise , Técnicas Eletroquímicas , Eletrodos , Escherichia coli O157 , Nanopartículas Metálicas/química , Nanopartículas/química , Propilaminas , Silanos , Titânio/química , Difração de Raios X
9.
Bioorg Chem ; 113: 105013, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34062405

RESUMO

AD is a progressive brain disorder. Because of the lack of remarkable single-target drugs against neurodegenerative disorders, the multitarget-directed ligand strategy has received attention as a promising therapeutic approach. Herein, we rationally designed twenty-nine hybrids of N-propargylamine-hydroxypyridinone. The designed hybrids possessed excellent iron-chelating activity (pFe3+ = 17.09-22.02) and potent monoamine oxidase B inhibitory effects. Various biological evaluations of the optimal compound 6b were performed step by step, including inhibition screening of monoamine oxidase (hMAO-B IC50 = 0.083 ± 0.001 µM, hMAO-A IC50 = 6.11 ± 0.08 µM; SI = 73.5), prediction of blood-brain barrier permeability and mouse behavioral research. All of these favorable results proved that the N-propargylamine-hydroxypyridinone scaffold is a promising structure for the discovery of multitargeted ligands for AD therapy.


Assuntos
Inibidores da Monoaminoxidase/química , Pargilina/análogos & derivados , Propilaminas/química , Piridinas/química , Doença de Alzheimer/tratamento farmacológico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Modelos Animais de Doenças , Desenho de Fármacos , Estabilidade de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Quelantes de Ferro/síntese química , Quelantes de Ferro/química , Quelantes de Ferro/farmacologia , Quelantes de Ferro/uso terapêutico , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Monoaminoxidase/química , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/uso terapêutico , Pargilina/química , Relação Estrutura-Atividade
10.
Angew Chem Int Ed Engl ; 60(34): 18742-18749, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34115447

RESUMO

Mitochondria are the subcellular bioenergetic organelles. The analysis of their morphology and topology is essential to provide useful information on their activity and metabolism. Herein, we report a label-free shadow electrochemiluminescence (ECL) microscopy based on the spatial confinement of the ECL-emitting reactive layer to image single living mitochondria deposited on the electrode surface. The ECL mechanism of the freely-diffusing [Ru(bpy)3 ]2+ dye with the sacrificial tri-n-propylamine coreactant restrains the light-emitting region to a micrometric thickness allowing to visualize individual mitochondria with a remarkable sharp negative optical contrast. The imaging approach named "shadow ECL" (SECL) reflects the negative imprint of the local diffusional hindrance of the ECL reagents by each mitochondrion. The statistical analysis of the colocalization of the shadow ECL spots with the functional mitochondria revealed by classical fluorescent biomarkers, MitoTracker Deep Red and the endogenous intramitochondrial NADH, validates the reported methodology. The versatility and extreme sensitivity of the approach are further demonstrated by visualizing single mitochondria, which remain hardly detectable with the usual biomarkers. Finally, by alleviating problems of photobleaching and phototoxicity associated with conventional microscopy methods, SECL microscopy should find promising applications in the imaging of subcellular structures.


Assuntos
Técnicas Eletroquímicas , Medições Luminescentes , Mitocôndrias/química , Biomarcadores/análise , Corantes Fluorescentes/química , Compostos Organometálicos/química , Propilaminas/química
11.
Chem Asian J ; 16(15): 2018-2021, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34109742

RESUMO

In this study, we report an efficient fabrication method for the membrane of a metal-organic framework (MOF) (Kgm-OEt) which is one kind of kagomé-type MOF with a two-dimensional (2D) sheet structure having one-dimensional (1D) channels suitable for separation of H2 from other larger gases. The Kgm-OEt seed layer was created on an Al2 O3 substrate using layer-by-layer (LBL) growth, then a membrane was fabricated by secondary growth. The membrane on a 3-aminopropyltriethoxysilane (APTEs)-treated substrate obtained in this method was continuous and defect-free with the crystal orientation suitable for gas transportation, while the membrane grown on an unmodified substrate was loosely packed with unfavorable crystal orientation.


Assuntos
Óxido de Alumínio/química , Estruturas Metalorgânicas/síntese química , Propilaminas/química , Silanos/química , Estruturas Metalorgânicas/química , Estrutura Molecular , Tamanho da Partícula , Porosidade , Propriedades de Superfície
12.
Am J Nurs ; 121(7): 24, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34156375

RESUMO

A rising number of cases of misuse and abuse of propylhexedrine (Benzedrex), an over-the-counter nasal decongestant, have been documented. Misuse of this drug can lead to serious and potentially fatal cardiac and psychiatric adverse effects.


Assuntos
Descongestionantes Nasais/efeitos adversos , Propilaminas/efeitos adversos , Humanos , Descongestionantes Nasais/administração & dosagem , Medicamentos sem Prescrição/efeitos adversos , Propilaminas/administração & dosagem , Propilaminas/farmacologia
13.
Int J Mol Sci ; 22(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064275

RESUMO

Sigma-1 receptor (chaperone Sigma1R) is an intracellular protein with chaperone functions, which is expressed in various organs, including the brain. Sigma1R participates in the regulation of physiological mechanisms of anxiety (Su, T. P. et al., 2016) and reactions to emotional stress (Hayashi, T., 2015). In 2006, fabomotizole (ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole dihydrochloride) was registered in Russia as an anxiolytic (Seredenin S. and Voronin M., 2009). The molecular targets of fabomotizole are Sigma1R, NRH: quinone reductase 2 (NQO2), and monoamine oxidase A (MAO-A) (Seredenin S. and Voronin M., 2009). The current study aimed to clarify the dependence of fabomotizole anxiolytic action on its interaction with Sigma1R and perform a docking analysis of fabomotizole interaction with Sigma1R. An elevated plus maze (EPM) test revealed that the anxiolytic-like effect of fabomotizole (2.5 mg/kg i.p.) administered to male BALB/c mice 30 min prior EPM exposition was blocked by Sigma1R antagonists BD-1047 (1.0 mg/kg i.p.) and NE-100 (1.0 mg/kg i.p.) pretreatment. Results of initial in silico study showed that fabomotizole locates in the active center of Sigma1R, reproducing the interactions with the site's amino acids common for established Sigma1R ligands, with the ΔGbind value closer to that of agonist (+)-pentazocine in the 6DK1 binding site.


Assuntos
Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Benzimidazóis/farmacologia , Chaperonas Moleculares/metabolismo , Morfolinas/farmacologia , Receptores sigma/metabolismo , Animais , Anisóis/farmacologia , Sítios de Ligação/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Etilenodiaminas/farmacologia , Ligantes , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Propilaminas/farmacologia , Federação Russa
14.
Bull Environ Contam Toxicol ; 107(3): 487-493, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34023927

RESUMO

Isopropylamine dodecylbenzene sulfonate (IDS) is a new kind of anionic surfactant (ANS). To preliminarily evaluate the aquatic toxicity of IDS, this study took gibel carp (Carassius auratus gibelio) as the research object. The well-acclimatized fish were divided into six groups and exposed to 0 mg/L, 0.5 mg/L, 1.0 mg/L, 2.0 mg/L, 4.0 mg/L, or 8.0 mg/L of IDS for 7, 14, 21 or 28 days. Our results showed that the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content of the liver were unaffected by IDS exposure, while glutathione peroxidase (GSH-Px) activity was significantly inhibited. Hepatic tissue exhibited pathological damage, characterized by nuclear migration and dissolution and cell boundary blurring. The results suggest that IDS does not cause oxidative stress in the liver, but cause hepatic histopathological damage. GSH-Px can be considered as a biomarker of IDS exposure in gibel carp.


Assuntos
Carpa Dourada , Estresse Oxidativo , Animais , Derivados de Benzeno , Fígado/metabolismo , Propilaminas , Tensoativos/metabolismo , Tensoativos/toxicidade
15.
J Am Chem Soc ; 143(17): 6423-6433, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33885283

RESUMO

Terminal unactivated alkynes are nowadays considered the golden standard for cysteine-reactive warheads in activity-based probes (ABPs) targeting cysteine deubiquitinating enzymes (DUBs). In this work, we study the versatility of the thiol-alkyne addition reaction in more depth. Contrary to previous findings with UCHL3, we now show that covalent adduct formation can progress with substituents on the terminal or internal alkyne position. Strikingly, acceptance of alkyne substituents is strictly DUB-specific as this is not conserved among members of the same subfamily. Covalent adduct formation with the catalytic cysteine residue was validated by gel analysis and mass spectrometry of intact ABP-treated USP16CDWT and catalytically inactive mutant USP16CDC205A. Bottom-up mass spectrometric analysis of the covalent adduct with a deuterated propargyl ABP provides mechanistic understanding of the in situ thiol-alkyne reaction, identifying the alkyne rather than an allenic intermediate as the reactive species. Furthermore, kinetic analysis revealed that introduction of (bulky/electron-donating) methyl substituents on the propargyl moiety decreases the rate of covalent adduct formation, thus providing a rational explanation for the commonly lower level of observed covalent adduct compared to unmodified alkynes. Altogether, our work extends the scope of possible propargyl derivatives in cysteine targeting ABPs from unmodified terminal alkynes to internal and substituted alkynes, which we anticipate will have great value in the development of ABPs with improved selectivity profiles.


Assuntos
Alcinos/química , Cisteína Proteases/química , Pargilina/análogos & derivados , Compostos de Sulfidrila/química , Enzimas Desubiquitinantes/química , Células HEK293 , Humanos , Pargilina/química , Propilaminas/química , Ubiquitina Tiolesterase/química
16.
Biosens Bioelectron ; 184: 113232, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33878593

RESUMO

Here, we show that nitrogen-doped carbon quantum dots (NCQDs) strongly inhibits the anodic electrochemiluminescence (ECL) signal of a tris(4,4'-dicarboxylic acid-2,2'-bipyridyl) ruthenium(II) (Ru(dcbpy)32+)/tripropylamine (TPA) aqueous system. To determine the ECL-quenching mechanism, we used photoluminescence spectroscopy, UV-Visible absorption spectroscopy and dynamic simulation technology. Quenching of the ECL signal of Ru(dcbpy)32+/TPA by NCQDs was predominantly attributed to the interaction between Ru(dcbpy)32+ and NCQDs rather than that between TPA and NCQDs. Specifically, when Ru(dcbpy)32+ and NCQDs were in aqueous solution together, the carboxyl (-COOH) groups of Ru(dcbpy)32+ were in contact with oxygen- and nitrogen-containing groups on the surface of NCQDs and formed intermolecular hydrogen bonds. This process involved energy transfer from the excited-state Ru(dcbpy)32+ to the intermolecular hydrogen bonds, thus resulting in a decrease in the Ru(dcbpy)32+ ECL signal. On this basis, a quenching-type ECL sensor for the quantification of NCQDs was fabricated. The sensor had a wide linear range and an estimated detection limit of 0.0012 mg mL-1, as well as excellent stability and selectivity. Satisfactory recoveries of 97.0-99.5% were obtained using the ECL sensor to quantify NCQDs in tap water. NCQDs could potentially be used as a quenching probe of Ru(dcbpy)32+ to construct various biosensors with widespread applications in the sensing field.


Assuntos
Técnicas Biossensoriais , Pontos Quânticos , Carbono , Técnicas Eletroquímicas , Hidrogênio , Medições Luminescentes , Nitrogênio , Propilaminas
17.
FASEB J ; 35(5): e21581, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33871072

RESUMO

Synaptic plasticity damages play a crucial role in the onset and development of depression, especially in the hippocampus, which is more susceptible to stress and the most frequently studied brain region in depression. And, mitochondria have a major function in executing the complex processes of neurotransmission and plasticity. We have previously demonstrated that Iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could improve the depressive-like behavior in mice. But the underlying mechanisms are not well understood. The present study demonstrated that Ipt reversed depressive-like phenotype in vivo (chronic mild stress-induced mice model of depression) and in vitro (corticosterone-induced cellular model). Further study showed that Ipt could upregulate the synaptic-related proteins postsynaptic density 95 (PSD 95) and synaptophysin (SYN), and alleviated the synaptic structure damage. Moreover, Ipt could reverse the abnormal mitochondrial fission and fusion, as well as the reduced mitochondrial ATP production and collapse of mitochondrial membrane potential in depressive models. Knocking down the mitochondrial ATP-sensitive potassium (Mito-KATP) channel subunit MitoK partly blocked the above effects of Ipt. Therefore, our results reveal that Ipt can alleviate the abnormal mitochondrial dynamics and function depending on MitoK, contributing to improve synaptic plasticity and exert antidepressive effects. These findings provide a candidate compound and a novel target for antidepressive therapy.


Assuntos
Depressão/tratamento farmacológico , Canais KATP/antagonistas & inibidores , Mitocôndrias/efeitos dos fármacos , Propilaminas/farmacologia , Estresse Psicológico/complicações , Sinapses/efeitos dos fármacos , Animais , Depressão/etiologia , Depressão/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Plasticidade Neuronal , Sinapses/metabolismo
18.
J Biol Chem ; 296: 100645, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33839156

RESUMO

Interactions of membrane-bound mammalian cytochromes P450 (CYPs) with NADPH-cytochrome P450 oxidoreductase (POR), which are required for metabolism of xenobiotics, are facilitated by membrane lipids. A variety of membrane mimetics, such as phospholipid liposomes and nanodiscs, have been used to simulate the membrane to form catalytically active CYP:POR complexes. However, the exact mechanism(s) of these interactions are unclear because of the absence of structural information of full-length mammalian CYP:POR complexes in membranes. Herein, we report the use of amphipols (APols) to form a fully functional, soluble, homogeneous preparation of full-length CYP:POR complexes amenable to biochemical and structural study. Incorporation of CYP2B4 and POR into APols resulted in a CYP2B4:POR complex with a stoichiometry of 1:1, which was fully functional in demethylating benzphetamine at a turnover rate of 37.7 ± 2.2 min-1, with a coupling efficiency of 40%. Interestingly, the stable complex had a molecular weight (Mw) of 338 ± 22 kDa determined by multiangle light scattering, suggestive of a tetrameric complex of 2CYP2B4:2POR embedded in one APol nanoparticle. Moreover, negative stain electron microscopy (EM) validated the homogeneity of the complex and allowed us to generate a three-dimensional EM map and model consistent with the tetramer observed in solution. This first report of the full-length mammalian CYP:POR complex by transmission EM not only reveals the architecture that facilitates electron transfer but also highlights a potential use of APols in biochemical and structural studies of functional CYP complexes with redox partners.


Assuntos
Hidrocarboneto de Aril Hidroxilases/metabolismo , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Polímeros/metabolismo , Propilaminas/metabolismo , Animais , Hidrocarboneto de Aril Hidroxilases/química , Catálise , Família 2 do Citocromo P450/química , Família 2 do Citocromo P450/metabolismo , NADPH-Ferri-Hemoproteína Redutase/química , Ligação Proteica , Conformação Proteica , Multimerização Proteica , Coelhos
19.
J Chromatogr A ; 1645: 462130, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-33848663

RESUMO

Inspired by the outstanding functions of 3-aminopropyltriethoxysilane (APTES), which can be used for functionalization of both covalent organic frameworks (COFs) and substrate surfaces, herein, a proof-of-concept demonstration was carried out by one-step synthesis and immobilization of COF-1 in capillary. COF-1 was grown on the inner wall of capillary using APTES, which played a triple role of catalyst, stabilizer, and connecting arm during the process. The immobilization of COF-1 on silicon surface was confirmed by scanning electron microscopy. Moreover, COF-1 modified capillary (COF-1@capillary) column exhibited excellent performance in the electrochromatographic separation of amino acids. High resolution and separation efficiency (225,378 plates/m for 4-methylbiphenyl) were successfully achieved. Separation of methylbenzene, styrene, ethylbenzene, chlorobenzene, 1,2-dichlorobenzene, 1,2,4-trichlorobenzene, 4-methylbiphenyl, naphthalene, and 4-vinylbipheny in the electro-driven mode confirmed the successful growth of COF-1 on the inner wall of capillary. The developed facile method for the immobilization of COF-1 may pave the way for further application prospects of boron-based COFs.


Assuntos
Eletrocromatografia Capilar/métodos , Estruturas Metalorgânicas/química , Derivados de Benzeno/análise , Derivados de Benzeno/química , Derivados de Benzeno/isolamento & purificação , Boro/química , Propilaminas/química , Silanos/química
20.
Molecules ; 26(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799713

RESUMO

Osteomyelitis and orthopedic infections are major clinical problems, limited by a lack of antibiotics specialized for such applications. In this paper, we describe the design and synthesis of a novel bone-binding antibiotic (BBA-1) and its subsequent structural and functional characterization. The synthesis of BBA-1 was the result of a two-step chemical conjugation of cationic selective antimicrobial-90 (CSA-90) and the bisphosphonate alendronate (ALN) via a heterobifunctional linker. This was analytically confirmed by HPLC, FT-IR, MS and NMR spectroscopy. BBA-1 showed rapid binding and high affinity to bone mineral in an in vitro hydroxyapatite binding assay. Kirby-Baur assays confirmed that BBA-1 shows a potent antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus comparable to CSA-90. Differentiation of cultured osteoblasts in media supplemented with BBA-1 led to increased alkaline phosphatase expression, which is consistent with the pro-osteogenic activity of CSA-90. Bisphosphonates, such as ALN, are inhibitors of protein prenylation, however, the amine conjugation of ALN to CSA-90 disrupted this activity in an in vitro protein prenylation assay. Overall, these findings support the antimicrobial, bone-binding, and pro-osteogenic activities of BBA-1. The compound and related agents have the potential to ensure lasting activity against osteomyelitis after systemic delivery.


Assuntos
Alendronato/química , Antibacterianos/síntese química , Osteomielite/tratamento farmacológico , Pregnanos/química , Propilaminas/química , Células 3T3 , Alendronato/farmacologia , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Osso e Ossos/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Difosfonatos/química , Difosfonatos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Pregnanos/farmacologia , Propilaminas/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos
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