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1.
Molecules ; 26(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205933

RESUMO

Biothiols are extremely powerful antioxidants that protect cells against the effects of oxidative stress. They are also considered relevant disease biomarkers, specifically risk factors for cardiovascular disease. In this paper, a new procedure for the simultaneous determination of human serum albumin and low-molecular-weight thiols in plasma is described. The method is based on the pre-column derivatization of analytes with a thiol-specific fluorescence labeling reagent, monobromobimane, followed by separation and quantification through reversed-phase high-performance liquid chromatography with fluorescence detection (excitation, 378 nm; emission, 492 nm). Prior to the derivatization step, the oxidized thiols are converted to their reduced forms by reductive cleavage with sodium borohydride. Linearity in the detector response for total thiols was observed in the following ranges: 1.76-30.0 mg mL-1 for human serum albumin, 0.29-5.0 nmol mL-1 for α-lipoic acid, 1.16-35 nmol mL-1 for glutathione, 9.83-450.0 nmol mL-1 for cysteine, 0.55-40.0 nmol mL-1 for homocysteine, 0.34-50.0 nmol mL-1 for N-acetyl-L-cysteine, and 1.45-45.0 nmol mL-1 for cysteinylglycine. Recovery values of 85.16-119.48% were recorded for all the analytes. The developed method is sensitive, repeatable, and linear within the expected ranges of total thiols. The devised procedure can be applied to plasma samples to monitor biochemical processes in various pathophysiological states.


Assuntos
Compostos Bicíclicos com Pontes/química , Albumina Sérica Humana/análise , Compostos de Sulfidrila/análise , Cromatografia de Fase Reversa , Humanos , Peso Molecular , Oxirredução , Albumina Sérica Humana/química , Compostos de Sulfidrila/química
2.
Mikrochim Acta ; 188(6): 199, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: covidwho-1245646

RESUMO

Since the COVID-19 disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) was declared a pandemic, it has spread rapidly, causing one of the most serious outbreaks in the last century. Reliable and rapid diagnostic tests for COVID-19 are crucial to control and manage the outbreak. Here, a label-free square wave voltammetry-based biosensing platform for the detection of SARS-CoV-2 in nasopharyngeal samples is reported. The sensor was constructed on screen-printed carbon electrodes coated with gold nanoparticles. The electrodes were functionalized using 11-mercaptoundecanoic acid (MUA) which was used for the immobilization of an antibody against SARS-CoV-2 nucleocapsid protein (N protein). The binding of the immunosensor with the N protein caused a change in the electrochemical signal. The detection was realised by measuring the change in reduction peak current of a redox couple using square wave voltammetry at 0.04 V versus Ag ref. electrode on the immunosensor upon binding with the N protein. The electrochemical immunosensor showed high sensitivity with a linear range from 1.0 pg.mL-1 to 100 ng.mL-1 and a limit of detection of 0.4 pg.mL-1 for the N protein in PBS buffer pH 7.4. Moreover, the immunosensor did not exhibit significant response with other viruses such as HCoV, MERS-CoV, Flu A and Flu B, indicating the high selectivity of the sensor for SARS-CoV-2. However, cross reactivity of the biosensor with SARS-CoV is indicated, which gives ability of the sensor to detect both SARS-CoV and SARS-CoV-2. The biosensor was successfully applied to detect the SARS-CoV-2 virus in clinical samples showing good correlation between the biosensor response and the RT-PCR cycle threshold values. We believe that the capability of miniaturization, low-cost and fast response of the proposed label-free electrochemical immunosensor will facilitate the point-of-care diagnosis of COVID 19 and help prevent further spread of infection.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Proteínas do Nucleocapsídeo de Coronavírus/análise , Técnicas Eletroquímicas/métodos , Imunoensaio/métodos , SARS-CoV-2/química , Anticorpos Imobilizados/imunologia , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Teste para COVID-19/instrumentação , Carbono/química , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Técnicas Eletroquímicas/instrumentação , Eletrodos , Ácidos Graxos/química , Ouro/química , Humanos , Imunoensaio/instrumentação , Limite de Detecção , Nanopartículas Metálicas/química , Nasofaringe/virologia , Fosfoproteínas/análise , Fosfoproteínas/imunologia , Compostos de Sulfidrila/química
3.
Mikrochim Acta ; 188(6): 199, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34041585

RESUMO

Since the COVID-19 disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) was declared a pandemic, it has spread rapidly, causing one of the most serious outbreaks in the last century. Reliable and rapid diagnostic tests for COVID-19 are crucial to control and manage the outbreak. Here, a label-free square wave voltammetry-based biosensing platform for the detection of SARS-CoV-2 in nasopharyngeal samples is reported. The sensor was constructed on screen-printed carbon electrodes coated with gold nanoparticles. The electrodes were functionalized using 11-mercaptoundecanoic acid (MUA) which was used for the immobilization of an antibody against SARS-CoV-2 nucleocapsid protein (N protein). The binding of the immunosensor with the N protein caused a change in the electrochemical signal. The detection was realised by measuring the change in reduction peak current of a redox couple using square wave voltammetry at 0.04 V versus Ag ref. electrode on the immunosensor upon binding with the N protein. The electrochemical immunosensor showed high sensitivity with a linear range from 1.0 pg.mL-1 to 100 ng.mL-1 and a limit of detection of 0.4 pg.mL-1 for the N protein in PBS buffer pH 7.4. Moreover, the immunosensor did not exhibit significant response with other viruses such as HCoV, MERS-CoV, Flu A and Flu B, indicating the high selectivity of the sensor for SARS-CoV-2. However, cross reactivity of the biosensor with SARS-CoV is indicated, which gives ability of the sensor to detect both SARS-CoV and SARS-CoV-2. The biosensor was successfully applied to detect the SARS-CoV-2 virus in clinical samples showing good correlation between the biosensor response and the RT-PCR cycle threshold values. We believe that the capability of miniaturization, low-cost and fast response of the proposed label-free electrochemical immunosensor will facilitate the point-of-care diagnosis of COVID 19 and help prevent further spread of infection.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Proteínas do Nucleocapsídeo de Coronavírus/análise , Técnicas Eletroquímicas/métodos , Imunoensaio/métodos , SARS-CoV-2/química , Anticorpos Imobilizados/imunologia , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Teste para COVID-19/instrumentação , Carbono/química , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Técnicas Eletroquímicas/instrumentação , Eletrodos , Ácidos Graxos/química , Ouro/química , Humanos , Imunoensaio/instrumentação , Limite de Detecção , Nanopartículas Metálicas/química , Nasofaringe/virologia , Fosfoproteínas/análise , Fosfoproteínas/imunologia , Compostos de Sulfidrila/química
4.
Nat Commun ; 12(1): 2994, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016981

RESUMO

Autocatalytic and oscillatory networks of organic reactions are important for designing life-inspired materials and for better understanding the emergence of life on Earth; however, the diversity of the chemistries of these reactions is limited. In this work, we present the thiol-assisted formation of guanidines, which has a mechanism analogous to that of native chemical ligation. Using this reaction, we designed autocatalytic and oscillatory reaction networks that form substituted guanidines from thiouronium salts. The thiouronium salt-based oscillator show good stability of oscillations within a broad range of experimental conditions. By using nitrile-containing starting materials, we constructed an oscillator where the concentration of a bicyclic derivative of dihydropyrimidine oscillates. Moreover, the mixed thioester and thiouronium salt-based oscillator show unique responsiveness to chemical cues. The reactions developed in this work expand our toolbox for designing out-of-equilibrium chemical systems and link autocatalytic and oscillatory chemistry to the synthesis of guanidinium derivatives and the products of their transformations including analogs of nucleobases.


Assuntos
Catálise , Guanidinas/química , Origem da Vida , Compostos de Sulfidrila/química , Ciclização
5.
Nat Commun ; 12(1): 3124, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035275

RESUMO

Linear nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) template the modular biosynthesis of numerous nonribosomal peptides, polyketides and their hybrids through assembly line chemistry. This chemistry can be complex and highly varied, and thus challenges our understanding in NRPS and PKS-programmed, diverse biosynthetic processes using amino acid and carboxylate building blocks. Here, we report that caerulomycin and collismycin peptide-polyketide hybrid antibiotics share an assembly line that involves unusual NRPS activity to engage a trans-acting flavoprotein in C-C bond formation and heterocyclization during 2,2'-bipyridine formation. Simultaneously, this assembly line provides dethiolated and thiolated 2,2'-bipyridine intermediates through differential treatment of the sulfhydryl group arising from L-cysteine incorporation. Subsequent L-leucine extension, which does not contribute any atoms to either caerulomycins or collismycins, plays a key role in sulfur fate determination by selectively advancing one of the two 2,2'-bipyridine intermediates down a path to the final products with or without sulfur decoration. These findings further the appreciation of assembly line chemistry and will facilitate the development of related molecules using synthetic biology approaches.


Assuntos
2,2'-Dipiridil/análogos & derivados , 2,2'-Dipiridil/química , Flavoproteínas/química , 2,2'-Dipiridil/síntese química , 2,2'-Dipiridil/metabolismo , Antibacterianos/química , Antibacterianos/metabolismo , Cisteína/química , Cisteína/metabolismo , Flavoproteínas/metabolismo , Compostos Heterocíclicos/química , Compostos Heterocíclicos/metabolismo , Modelos Químicos , Estrutura Molecular , Peptídeo Sintases/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Policetídeo Sintases/metabolismo , Policetídeos/química , Policetídeos/metabolismo , Compostos de Sulfidrila/química , Compostos de Sulfidrila/metabolismo
6.
Arch Toxicol ; 95(4): 1179-1226, 2021 04.
Artigo em Inglês | MEDLINE | ID: covidwho-1162995

RESUMO

Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.


Assuntos
Compostos Organosselênicos/farmacologia , Compostos Organosselênicos/toxicidade , Aminoácidos/química , Animais , Azóis , Humanos , Estrutura Molecular , Selênio/química , Selênio/fisiologia , Selenoproteínas/química , Compostos de Sulfidrila/química
7.
Molecules ; 26(8)2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33920567

RESUMO

Due to the redox properties closely related to numerous physiological and pathological processes, biothiols, including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), have received considerable attention in biological science. On account of the important physiological roles of these biothiols, it is of profound significance to develop sensitive and selective detection of biothiols to understand their biological profiles. In this work, we reported an efficient fluorescent probe, PHPQ-SH, for detecting biothiols in vitro and vivo, based on the phenothiazine-HPQ skeleton, with DNBS (2,4-dinitrobenzenesulfonate) as the response unit. Probe PHPQ-SH exhibited brilliant sensing performances toward thiols, including a large Stokes shift (138 nm), excellent sensitivity (for GSH, LOD = 18.3 nM), remarkable fluorescence enhancement (163-fold), low cytotoxicity, rapid response (8 min), and extraordinary selectivity. Finally, the probe PHPQ-SH illustrated herein was capable of responding and visualizing biothiols in MCF-7 cells and zebrafish.


Assuntos
Técnicas Biossensoriais , Corantes Fluorescentes/isolamento & purificação , Quinazolinonas/química , Compostos de Sulfidrila/isolamento & purificação , Animais , Corantes Fluorescentes/química , Glutationa/química , Células HeLa , Humanos , Células MCF-7 , Imagem Óptica , Fenotiazinas , Compostos de Sulfidrila/química , Peixe-Zebra
8.
Molecules ; 26(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806630

RESUMO

While thiol-based catalysts are widely employed for chemical protein synthesis relying on peptide thioester chemistry, this is less true for selenol-based catalysts whose development is in its infancy. In this study, we compared different selenols derived from the selenocysteamine scaffold for their capacity to promote thiol-thioester exchanges in water at mildly acidic pH and the production of peptide thioesters from bis(2-sulfanylethyl)amido (SEA) peptides. The usefulness of a selected selenol compound is illustrated by the total synthesis of a biologically active human chemotactic protein, which plays an important role in innate and adaptive immunity.


Assuntos
Fatores Quimiotáticos/metabolismo , Quimiotaxia , Ésteres/síntese química , Compostos Organosselênicos/química , Fragmentos de Peptídeos/química , Biossíntese de Proteínas , Compostos de Sulfidrila/química , Catálise , Técnicas de Química Sintética , Humanos , Monócitos/citologia , Monócitos/fisiologia
9.
Molecules ; 26(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33926119

RESUMO

Glutathionyl hemoglobin is a minor form of hemoglobin with intriguing properties. The measurement of the redox potential of its reactive ß-93-Cysteine is useful to improve understanding of the response of erythrocytes to transient and chronic conditions of oxidative stress, where the level of glutathionyl hemoglobin is increased. An independent literature experiment describes the recovery of human erythrocytes exposed to an oxidant burst by measuring glutathione, glutathione disulfide and glutathionyl hemoglobin in a two-hour period. This article calculates a value for the redox potential E0 of the ß-93-Cysteine, considering the erythrocyte as a closed system at equilibrium described by the Nernst equation and using the measurements of the literature experiment. The obtained value of E0 of -121 mV at pH 7.4 places hemoglobin as the most oxidizing thiol of the erythrocyte. By using as synthetic indicators of the concentrations the electrochemical potentials of the two main redox pairs in the erythrocytes, those of glutathione-glutathione disulfide and of glutathionyl-hemoglobin, the mechanism of the recovery phase can be hypothesized. Hemoglobin acts as the redox buffer that scavenges oxidized glutathione in the oxidative phase and releases it in the recovery phase, by acting as the substrate of the NAD(P)H-cofactored enzymes.


Assuntos
Cisteína/química , Hemoglobinas/química , Oxidantes/química , Oxirredução , Compostos de Sulfidrila/química , Fenômenos Químicos , Eritrócitos/química , Eritrócitos/metabolismo , Glutationa/química , Glutationa/metabolismo , Dissulfeto de Glutationa/química , Hemoglobinas/metabolismo , Humanos , Peróxido de Hidrogênio/química , Cinética , Modelos Biológicos , Oxidantes/farmacologia , Oxirredução/efeitos dos fármacos , Estresse Oxidativo
10.
Int J Mol Sci ; 22(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925645

RESUMO

S-nitrosylation is a selective and reversible post-translational modification of protein thiols by nitric oxide (NO), which is a bioactive signaling molecule, to exert a variety of effects. These effects include the modulation of protein conformation, activity, stability, and protein-protein interactions. S-nitrosylation plays a central role in propagating NO signals within a cell, tissue, and tissue microenvironment, as the nitrosyl moiety can rapidly be transferred from one protein to another upon contact. This modification has also been reported to confer either tumor-suppressing or tumor-promoting effects and is portrayed as a process involved in every stage of cancer progression. In particular, S-nitrosylation has recently been found as an essential regulator of the tumor microenvironment (TME), the environment around a tumor governing the disease pathogenesis. This review aims to outline the effects of S-nitrosylation on different resident cells in the TME and the diverse outcomes in a context-dependent manner. Furthermore, we will discuss the therapeutic potentials of modulating S-nitrosylation levels in tumors.


Assuntos
Óxido Nítrico/química , Compostos de Sulfidrila/química , Microambiente Tumoral/fisiologia , Animais , Fenômenos Bioquímicos , Cisteína/química , Humanos , Neoplasias/metabolismo , Óxido Nítrico/metabolismo , Mapeamento de Interação de Proteínas/métodos , Processamento de Proteína Pós-Traducional , Proteínas/metabolismo , Transdução de Sinais , Compostos de Sulfidrila/metabolismo
11.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802614

RESUMO

In this study, dense gold-assembled SiO2 nanostructure (SiO2@Au) was successfully developed using the Au seed-mediated growth. First, SiO2 (150 nm) was prepared, modified by amino groups, and incubated by gold nanoparticles (ca. 3 nm Au metal nanoparticles (NPs)) to immobilize Au NPs to SiO2 surface. Then, Au NPs were grown on the prepared SiO2@Au seed by reducing chloroauric acid (HAuCl4) by ascorbic acid (AA) in the presence of polyvinylpyrrolidone (PVP). The presence of bigger (ca. 20 nm) Au NPs on the SiO2 surface was confirmed by transmittance electronic microscopy (TEM) images, color changes to dark blue, and UV-vis spectra broadening in the range of 450 to 750 nm. The SiO2@Au nanostructure showed several advantages compared to the hydrofluoric acid (HF)-treated SiO2@Au, such as easy separation, surface modification stability by 11-mercaptopundecanoic acid (R-COOH), 11-mercapto-1-undecanol (R-OH), and 1-undecanethiol (R-CH3), and a better peroxidase-like catalysis activity for 5,5'-Tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2) reaction. The catalytic activity of SiO2@Au was two times better than that of HF-treated SiO2@Au. When SiO2@Au nanostructure was used as a surface enhanced Raman scattering (SERS) substrate, the signal of 4-aminophenol (4-ATP) on the surface of SiO2@Au was also stronger than that of HF-treated SiO2@Au. This study provides a potential method for nanoparticle preparation which can be replaced for Au NPs in further research and development.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Nanoestruturas/química , Dióxido de Silício/química , Aminofenóis/química , Benzidinas/química , Técnicas Biossensoriais/métodos , Catálise , Ácido Fluorídrico/química , Peróxido de Hidrogênio/química , Limite de Detecção , Povidona/química , Prata/química , Compostos de Sulfidrila/química
12.
J Chromatogr A ; 1645: 462122, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-33853010

RESUMO

Silver(I)-mercaptopropyl (Ag-MP) functionalized silica gel has demonstrated its effectiveness in separating various unsaturated organic compounds including unsaturated fatty acid ethyl esters (FAEEs), triglycerols (TAGs) and long-chain alkyl ketones (alkenones). While Ag-MP stationary phase displays many advantages over the conventional silver ion-impregnated silica gel (e.g., stability, high recovery, etc.), potential drawbacks of Ag-MP include relatively low retentions for unsaturated molecules, which could limit chromatographic resolutions under certain circumstances. In this study, we evaluate a new silver-thiolate stationary phase: silver(I)-dimercaptotriazine (Ag-DMT) functionalized silica gel targeting the separation of unsaturated compounds. We show Ag-DMT affords substantially higher retention factors, peak resolutions and capacities for TAGs and FAEEs than Ag-MP does. Ag-DMT also yields higher purity eicosapentaenoic acid (EPA) from fish oil FAEE mixtures than Ag-MP. In addition, Ag-DMT resolves double bond positional and cis/trans-isomers of C18:1 fatty acid methyl esters (FAMEs) as well as unsaturated methyl/ethyl alkenones with different number of double bonds. Based on van't Hoff plots, enthalpy changes during the adsorption of unsaturated FAEEs onto Ag-DMT are ~2 times higher than those on Ag-MP. Such difference may be attributed to the stronger electron-withdrawing effect of the thiol group on DMT, which results in more positively charged silver ions hence greater interactions with unsaturated molecules. The stronger interaction between double bonds and Ag-DMT is further corroborated by density-functional theory (DFT) calculations. Ag-DMT shows its high stability for repeated uses in the separation of TAGs over 319 runs, with peak resolutions decreasing by < 3%. Collectively, our data demonstrate the exceptionally high efficiency of Ag-DMT column for separating unsaturated molecules.


Assuntos
Cromatografia Líquida/métodos , Compostos de Prata/química , Compostos de Sulfidrila/química , Triazinas/química , Ácidos Graxos Insaturados/análise , Ácidos Graxos Insaturados/isolamento & purificação , Ácidos Graxos Insaturados/metabolismo , Compostos de Prata/metabolismo , Compostos de Sulfidrila/metabolismo , Triazinas/metabolismo
13.
Arch Toxicol ; 95(4): 1179-1226, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33792762

RESUMO

Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.


Assuntos
Compostos Organosselênicos/farmacologia , Compostos Organosselênicos/toxicidade , Aminoácidos/química , Animais , Azóis , Humanos , Estrutura Molecular , Selênio/química , Selênio/fisiologia , Selenoproteínas/química , Compostos de Sulfidrila/química
14.
Inorg Chem ; 60(8): 5413-5418, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33788549

RESUMO

We report a new scheme for chiral recognition using coordination polymers of Ag+ with a chiral thiol ligand that contains a binding group. N-Benzoyl-l-cysteine ethyl ester equipped with a boronic acid group at the para position of the phenyl ring forms coordination polymers with Ag+ in alkaline aqueous solutions that exhibit excellent selectivity toward a d-glucose enantiomer over l-glucose, while the coordination polymers from the d-cysteine-based thiol ligand are specific for l-glucose. It is assumed that a conformation change occurs upon interaction of a saccharide molecule with the polymeric chain receptor, for which the next binding is promoted, leading to the highly effective chiral recognition, despite the flexible nature of the polymeric receptor.


Assuntos
Complexos de Coordenação/química , Cisteína/química , Glucose/análise , Polímeros/química , Prata/química , Compostos de Sulfidrila/química , Sítios de Ligação , Complexos de Coordenação/síntese química , Ligantes , Estrutura Molecular
15.
Org Biomol Chem ; 19(12): 2753-2766, 2021 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-33687423

RESUMO

The modulation of SK3 ion channels can be efficiently and selectively achieved by using the amphiphilic compound Ohmline (a glyco-glycero-ether-lipid). We report herein a series of Ohmline analogues featuring the replacement of one ether function by a thioether function located at the same position or shifted close to its initial position. The variation of the lipid chain length and the preparation of two analogues featuring either one sulfoxide or one sulfone moiety complete this series. Patch clamp measurements indicate that the presence of the thioether function (compounds 7 and 17a) produces strong activators of SK3 channels, whereas the introduction of a sulfoxide or a sulfone function at the same place produces amphiphiles devoid of an effect on SK3 channels. Compounds 7 and 17a are the first amphiphilic compounds featuring strong activation of SK3 channels (close to 200% activation). The cytosolic calcium concentration determined from fluorescence at 3 different times for compound 7b (13 min, 1 h, 24 h) revealed that the effect is different suggesting that the compound could be metabolized over time. This compound could be used as a strong SK3 activator for a short time. The capacity of 7b to activate SK3 was then used to induce vasorelaxation via an endothelium-derived hyperpolarization (EDH) pathway. For the first time, we report that an amphiphilic compound can affect the endothelium dependent vasorelaxation.


Assuntos
Éteres/farmacologia , Glicolipídeos/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo , Compostos de Sulfidrila/farmacologia , Tensoativos/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Éteres/química , Glicolipídeos/química , Humanos , Masculino , Ratos , Ratos Wistar , Compostos de Sulfidrila/química , Tensoativos/síntese química , Tensoativos/química , Vasodilatação/efeitos dos fármacos
16.
Eur J Med Chem ; 217: 113326, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33756127

RESUMO

Defective in cullin neddylation 1(DCN1) is a co-E3 ligase that is important for cullin neddylation. Dysregulation of DCN1 highly correlates with the development of various cancers. Herein, from the initial high-throughput screening, a novel hit compound 5a containing a phenyltriazole thiol core (IC50 value of 0.95 µM for DCN1-UBC12 interaction) was discovered. Further structure-based optimization leads to the development of SK-464 (IC50 value of 26 nM). We found that SK-464 not only directly bound to DCN1 in vitro, but also engaged cellular DCN1, suppressed the neddylation of cullin3, and hindered the migration and invasion of two DCN1-overexpressed squamous carcinoma cell lines (KYSE70 and H2170). These findings indicate that SK-464 may be a novel lead compound targeting DCN1-UBC12 interaction.


Assuntos
Desenvolvimento de Medicamentos , Inibidores Enzimáticos/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Compostos de Sulfidrila/farmacologia , Triazóis/farmacologia , Enzimas de Conjugação de Ubiquitina/antagonistas & inibidores , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/química , Triazóis/síntese química , Triazóis/química , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo
17.
Food Chem ; 353: 129453, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33765599

RESUMO

This study investigated the effects of transglutaminase (TGase) on the properties of myofibrillar protein (MP) and its heat-induced gels under malondialdehyde (MDA)-induced oxidation. The physicochemical characteristics, protein aggregation and rheological properties of MP were assessed. The gelling behaviours of MP were analysed with measurements of gel strength, cooking loss, microstructure and secondary structure. Under varying degrees of MDA oxidation, the addition of TGase always led to changes in the tertiary structure, loss of free amine and thiol groups, crosslinking of the myosin heavy chain, and decreasing solubility. However, the effect of TGase on MP gel quality differed. At 6 mmol/L MDA, the addition of TGase reduced the quality of MP gels by increasing cooking loss. However, at 12 mmol/L MDA, TGase reduced both the cooking loss and gel strength.


Assuntos
Malondialdeído/química , Proteínas de Carne/química , Transglutaminases/química , Animais , Culinária , Géis/química , Temperatura Alta , Malondialdeído/metabolismo , Proteínas de Carne/metabolismo , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Miofibrilas/química , Cadeias Pesadas de Miosina/química , Oxirredução , Estresse Oxidativo , Carne de Porco , Estrutura Secundária de Proteína , Reologia , Solubilidade , Compostos de Sulfidrila/química , Suínos , Transglutaminases/metabolismo
18.
Food Chem ; 352: 129398, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33652197

RESUMO

We investigated the effects of ultrasonic treatment (400 W, 20 kHz, 45.52 W/L) and storage time (0 d, 3 d, 7 d and 10 d) on functional properties, structural changes and in vitro digestion of actomyosin complex isolated from vacuum-packed pork. As storage time increased, turbidity, surface hydrophobicity, active sulfhydryl and total sulfhydryl of actomyosin complex increased, while protein solubility decreased. Ultrasonic treatment increased surface hydrophobicity, protein solubility and active sulfhydryl content but decreased turbidity and total sulfhydryl content compared with the control. Ultrasonic treatment caused a reduction in α-helix content on 0 day and the fluorescence intensity of tryptophan and tyrosine residues. It increased pancreatin digestibility of actomyosin complex and the number of peptides of smaller than 1 kDa. However, it decreased the number of peptides. The findings provide a new insight into the application of appropriate ultrasonic treatment to promote meat digestibility.


Assuntos
Actomiosina/química , Digestão , Armazenamento de Alimentos , Carne/análise , Ondas Ultrassônicas , Actomiosina/metabolismo , Animais , Interações Hidrofóbicas e Hidrofílicas , Solubilidade , Compostos de Sulfidrila/química , Suínos
19.
Carbohydr Polym ; 260: 117843, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33712117

RESUMO

In this study, trehalose (TRE) was added to prepare whey protein concentrate (WPC)/pullulan (PUL)/TRE hydrogel and the hydrogel was used as the wall material to improve the viability of encapsulated L. plantarum during freeze drying and storage. The optimum conditions were 5.0 % TRE concentration and 1:4 (v:v) of the ratio of L. plantarum suspension to the hydrogel. Under these conditions, the survival rates of L. plantarum were 94.36 ± 1.06 % after freeze drying and 97.02 ± 0.30 % after storage for 240 d at 4 °C. Interactions and rheological properties of WPC/PUL/TRE hydrogel were also studied. The results showed TRE reduced storage modulus (G') of the hydrogel and weakened hydrophobic interactions, disulfide and hydrogen bonds between proteins and polysaccharides, which was not conducive to hydrogel formation. In addition, the excellent water-holding capacity of WPC/PUL/TRE hydrogel was found by the drying kinetic experiment.


Assuntos
Glucanos/química , Hidrogéis/química , Lactobacillus plantarum/fisiologia , Trealose/química , Proteínas do Soro do Leite/química , Liofilização , Hidrogéis/farmacologia , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Viabilidade Microbiana/efeitos dos fármacos , Reologia , Compostos de Sulfidrila/química
20.
J Chromatogr A ; 1642: 462028, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33721814

RESUMO

Measurement of chiral thiol compounds such as glutathione (GSH), cysteine (Cys), and homocysteine (Hcy) in human serum plays an important role in the early diagnosis and warning of cardiovascular disease, neurodegenerative disease, and cancer. We developed a novel chiral mass spectrometry derivatization reagent, (R)-(5-(3-isothiocyanatopyrrolidin-1-yl)-5-oxopentyl) triphenylphosphonium (NCS-OTPP), with triphenylphosphine (TPP) as a basic structure carrying a permanent positive charge for the diastereomeric separation of chiral thiol compounds by ultrahigh-performance liquid chromatography coupled to quadrupole-Orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). A novel method was developed for simultaneous determination of three kinds of chiral thiol compounds based on the NCS-OTPP derivatization method. Three kinds of chiral thiol compounds on a YMC Triart C18 (2.0 × 150 mm, 1.9 µm) column with Rs were 1.56-1.68. The protonated precursor to product ion transitions monitored for GSH was m/z 780.16→747.24/473.18, Cys was m/z 594.20→561.18/473.18, and Hcy was m/z 608.21→575.19/473.18. An excellent linearity for all the analytes with correlation coefficients ≥ 0.9995 and suitable precision with inter-day and intra-day coefficients of variation RSDs was 0.83-4.06% and 0.95-3.11%. Satisfactory accuracy with recoveries between 83.73 and 103.35% was observed. The limit of detection (S/N = 3) was 2.4-7.2 fmol. Furthermore, the method was successfully applied to the simultaneous determination of three kinds of free and total thiol compounds in serum from 10 healthy volunteers at normal and stress states.


Assuntos
Espectrometria de Massas/métodos , Estresse Psicológico/sangue , Compostos de Sulfidrila/sangue , Compostos de Sulfidrila/química , Adulto , Calibragem , Cromatografia Líquida de Alta Pressão , Feminino , Voluntários Saudáveis , Humanos , Limite de Detecção , Masculino , Compostos Organofosforados/síntese química , Compostos Organofosforados/química , Reprodutibilidade dos Testes , Estatística como Assunto , Estereoisomerismo , Fatores de Tempo , Adulto Jovem
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