Base de dados : MEDLINE
Pesquisa : D27.720.470.410.700 [Categoria DeCS]
Referências encontradas : 4080 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 408 ir para página                         

  1 / 4080 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29342154
[Au] Autor:Díaz-Mazariegos S; Cabrera N; Perez-Montfort R
[Ad] Endereço:Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, México.
[Ti] Título:Three unrelated and unexpected amino acids determine the susceptibility of the interface cysteine to a sulfhydryl reagent in the triosephosphate isomerases of two trypanosomes.
[So] Source:PLoS One;13(1):e0189525, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Proteins with great sequence similarity usually have similar structure, function and other physicochemical properties. But in many cases, one or more of the physicochemical or functional characteristics differ, sometimes very considerably, among these homologous proteins. To better understand how critical amino acids determine quantitative properties of function in proteins, the responsible residues must be located and identified. This can be difficult to achieve, particularly in cases where multiple amino acids are involved. In this work, two triosephosphate isomerases with very high similarity from two related human parasites were used to address one such problem. We demonstrate that a seventy-fold difference in the reactivity of an interface cysteine to the sulfhydryl reagent methylmethane sulfonate in these two enzymes depends on three amino acids located far away from this critical residue and which could not have been predicted using other current methods. Starting from previous observations with chimeric proteins involving these two triosephosphate isomerases, we developed a strategy involving additive mutant enzymes and selected site directed mutants to locate and identify the three amino acids. These three residues seem to induce changes in the interface cysteine in reactivity by increasing (or decreasing) its apparent pKa. Some enzymes with four to seven mutations also exhibited altered reactivity. This study completes a strategy for identifying key residues in the sequences of proteins that can have applications in future protein structure-function studies.
[Mh] Termos MeSH primário: Aminoácidos/química
Cisteína/química
Reagentes de Sulfidrila/química
Triose-Fosfato Isomerase/química
Trypanosoma/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Aminoácidos/genética
Modelos Moleculares
Mutagênese Sítio-Dirigida
Homologia de Sequência de Aminoácidos
Triose-Fosfato Isomerase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amino Acids); 0 (Sulfhydryl Reagents); EC 5.3.1.1 (Triose-Phosphate Isomerase); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189525


  2 / 4080 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28520393
[Au] Autor:Sameshima T; Tanaka Y; Miyahisa I
[Ad] Endereço:Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , 26-1, Muraoka-higashi 2 chome, Fujisawa, Kanagawa, Japan.
[Ti] Título:Universal and Quantitative Method To Evaluate Inhibitor Potency for Cysteinome Proteins Using a Nonspecific Activity-Based Protein Profiling Probe.
[So] Source:Biochemistry;56(23):2921-2927, 2017 Jun 13.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recently, there have been a limited number of new, validated targets for small-molecule drug discovery in the pharmaceutical industry. Although there are approximately 30 000 genes in the human genome, only 2% are targeted by currently approved small-molecule drugs. One reason that many targets remain neglected by drug discovery programs is the absence of biochemical assays enabling evaluation of the potency of inhibitors in a quantitative and high-throughput manner. To overcome this issue, we developed a biochemical assay to evaluate the potency of both reversible and irreversible inhibitors using a nonspecific thiol-labeling fluorescent probe. The assay can be applied to any targets with a cysteine residue in a pocket that can accommodate small-molecule ligands. By constructing a mathematical model, we showed that the potency of compounds can be quantitatively evaluated by performing an activity-based protein profiling assay. In addition, the validity of the theory was confirmed experimentally using epidermal growth factor receptor kinase as a model target. This approach provides an assay system for targets for which biochemical assays cannot be developed. Our approach can potentially not only expand the number of exploitable targets but also accelerate the lead optimization process by providing quantitative structure-activity relationship information.
[Mh] Termos MeSH primário: Compostos de Boro/metabolismo
Descoberta de Drogas/métodos
Corantes Fluorescentes/metabolismo
Maleimidas/metabolismo
Modelos Moleculares
Inibidores de Proteínas Quinases/farmacologia
Receptor do Fator de Crescimento Epidérmico/antagonistas & inibidores
Reagentes de Sulfidrila/metabolismo
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Ligação Competitiva
Biocatálise
Compostos de Boro/química
Domínio Catalítico
Cisteína/química
Transferência Ressonante de Energia de Fluorescência
Corantes Fluorescentes/química
Ensaios de Triagem em Larga Escala
Seres Humanos
Cinética
Ligantes
Maleimidas/química
Conformação Molecular
Fragmentos de Peptídeos/antagonistas & inibidores
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Inibidores de Proteínas Quinases/química
Inibidores de Proteínas Quinases/metabolismo
Relação Quantitativa Estrutura-Atividade
Receptor do Fator de Crescimento Epidérmico/química
Receptor do Fator de Crescimento Epidérmico/genética
Receptor do Fator de Crescimento Epidérmico/metabolismo
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Células Sf9
Spodoptera
Reagentes de Sulfidrila/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Boron Compounds); 0 (Fluorescent Dyes); 0 (Ligands); 0 (Maleimides); 0 (Peptide Fragments); 0 (Protein Kinase Inhibitors); 0 (Recombinant Fusion Proteins); 0 (Sulfhydryl Reagents); 0 (o-maleimide BODIPY); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170706
[Lr] Data última revisão:
170706
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00190


  3 / 4080 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28487364
[Au] Autor:Heirbaut M; Lermyte F; Martin EM; Beelen S; Sobott F; Strelkov SV; Weeks SD
[Ad] Endereço:From the Laboratory for Biocrystallography, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.
[Ti] Título:Specific sequences in the N-terminal domain of human small heat-shock protein HSPB6 dictate preferential hetero-oligomerization with the orthologue HSPB1.
[So] Source:J Biol Chem;292(24):9944-9957, 2017 Jun 16.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Small heat-shock proteins (sHSPs) are a conserved group of molecular chaperones with important roles in cellular proteostasis. Although sHSPs are characterized by their small monomeric weight, they typically assemble into large polydisperse oligomers that vary in both size and shape but are principally composed of dimeric building blocks. These assemblies can include different sHSP orthologues, creating additional complexity that may affect chaperone activity. However, the structural and functional properties of such hetero-oligomers are poorly understood. We became interested in hetero-oligomer formation between human heat-shock protein family B (small) member 1 (HSPB1) and HSPB6, which are both highly expressed in skeletal muscle. When mixed , these two sHSPs form a polydisperse oligomer array composed solely of heterodimers, suggesting preferential association that is determined at the monomer level. Previously, we have shown that the sHSP N-terminal domains (NTDs), which have a high degree of intrinsic disorder, are essential for the biased formation. Here we employed iterative deletion mapping to elucidate how the NTD of HSPB6 influences its preferential association with HSPB1 and show that this region has multiple roles in this process. First, the highly conserved motif RLFDQ FG is necessary for subunit exchange among oligomers. Second, a site ∼20 residues downstream of this motif determines the size of the resultant hetero-oligomers. Third, a region unique to HSPB6 dictates the preferential formation of heterodimers. In conclusion, the disordered NTD of HSPB6 helps regulate the size and stability of hetero-oligomeric complexes, indicating that terminal sHSP regions define the assembly properties of these proteins.
[Mh] Termos MeSH primário: Proteínas de Choque Térmico HSP20/metabolismo
Proteínas de Choque Térmico HSP27/metabolismo
Modelos Moleculares
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Substituição de Aminoácidos
Sequência Conservada
Reagentes para Ligações Cruzadas/farmacologia
Dimerização
Deleção de Genes
Proteínas de Choque Térmico HSP20/química
Proteínas de Choque Térmico HSP20/genética
Proteínas de Choque Térmico HSP27/química
Proteínas de Choque Térmico HSP27/genética
Seres Humanos
Mutagênese Sítio-Dirigida
Isótopos de Nitrogênio
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Mutação Puntual
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
Multimerização Proteica
Estabilidade Proteica
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Espalhamento a Baixo Ângulo
Reagentes de Sulfidrila/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cross-Linking Reagents); 0 (HSP20 Heat-Shock Proteins); 0 (HSP27 Heat-Shock Proteins); 0 (HSPB1 protein, human); 0 (HSPB6 protein, human); 0 (Nitrogen Isotopes); 0 (Peptide Fragments); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 0 (Sulfhydryl Reagents)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170706
[Lr] Data última revisão:
170706
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170511
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.773515


  4 / 4080 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28394577
[Au] Autor:Goulet DR; Zwolak A; Chiu ML; Nath A; Atkins WM
[Ad] Endereço:Department of Medicinal Chemistry, University of Washington , Seattle, Washington 98195-7631, United States.
[Ti] Título:Diffusion of Soluble Aggregates of THIOMABs and Bispecific Antibodies in Serum.
[So] Source:Biochemistry;56(17):2251-2260, 2017 May 02.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Submicrometer aggregates are frequently present at low levels in antibody-based therapeutics. Although intuition suggests that the fraction of the aggregate or the size of the aggregate present might correlate with deleterious clinical properties or formulation difficulties, it has been challenging to demonstrate which aggregate states, if any, trigger specific biological effects. One source of uncertainty about the putative linkage between aggregation and safety or efficacy lies in the likelihood that noncovalent aggregation differs in ideal buffers versus in serum and biological tissues; self-association or association with other proteins may vary widely with environment. Therefore, methods for monitoring aggregation and aggregate behavior in biologically relevant matrices could provide a tool for better predicting aggregate-dependent clinical outcomes and provide a basis for antibody engineering prior to clinical studies. Here, we generate models for soluble aggregates of THIOMABs and a bispecific antibody (bsAb) of defined size and exploit fluorescence correlation spectroscopy to monitor their diffusion properties in serum and viscosity-matched buffers. The monomers, dimers, and trimers of both THIOMABs and a bsAb reveal a modest increase in diffusion time in serum greater than expected for an increase in viscosity alone. A mixture of larger aggregates containing mostly bsAb pentamers exhibits a marked increase in diffusion time in serum and much greater intrasample variability, consistent with significant aggregation or interactions with serum components. The results indicate that small aggregates of several IgG platforms are not likely to aggregate with serum components, but nanometer-scale aggregates larger than trimers can interact with the serum in an Ab-dependent manner.
[Mh] Termos MeSH primário: Anticorpos Biespecíficos/química
Proteínas Sanguíneas/química
Imunoglobulina G/química
Agregados Proteicos
Trastuzumab/química
[Mh] Termos MeSH secundário: Algoritmos
Anticorpos Biespecíficos/efeitos adversos
Anticorpos Biespecíficos/análise
Anticorpos Biespecíficos/genética
Proteínas Sanguíneas/análise
Reagentes para Ligações Cruzadas/farmacologia
Difusão
Ditiotreitol/farmacologia
Composição de Medicamentos
Glutaral/farmacologia
Seres Humanos
Hidrodinâmica
Imunoglobulina G/efeitos adversos
Imunoglobulina G/análise
Imunoglobulina G/genética
Peso Molecular
Tamanho da Partícula
Proteínas Recombinantes/efeitos adversos
Proteínas Recombinantes/análise
Proteínas Recombinantes/química
Reprodutibilidade dos Testes
Solubilidade
Reagentes de Sulfidrila/farmacologia
Trastuzumab/efeitos adversos
Trastuzumab/análise
Viscosidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Bispecific); 0 (Blood Proteins); 0 (Cross-Linking Reagents); 0 (Immunoglobulin G); 0 (Protein Aggregates); 0 (Recombinant Proteins); 0 (Sulfhydryl Reagents); P188ANX8CK (Trastuzumab); T3C89M417N (Glutaral); T8ID5YZU6Y (Dithiothreitol)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170411
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.6b01097


  5 / 4080 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28366823
[Au] Autor:Yamauchi K; Ebihara Y; Kawakami Y
[Ad] Endereço:Department of Laboratory Medicine, Faculty of Medicine, University of Tsukuba, Japan; Department of Medical Sciences, Faculty of Medicine, University of Tsukuba, Japan. Electronic address: yamauchi@md.tsukuba.ac.jp.
[Ti] Título:Redox status of serum apolipoprotein E and its impact on HDL cholesterol levels.
[So] Source:Clin Biochem;50(13-14):777-783, 2017 Sep.
[Is] ISSN:1873-2933
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Apolipoprotein E (apoE) is closely involved in the pathogenesis of apoE-related diseases, such as Alzheimer's disease and cardiovascular disease. The redox modulation of cysteine-thiols in a protein is involved in various pathophysiological regulations; however, that of apoE has not been studied in detail. Herein, we devised an analytical method to determine the redox status of serum apoE and assessed its relation to serum cholesterol levels and apoE phenotype. METHODS: The present method was based on a band shift assay, using a photocleavable maleimide-conjugated polyethylene glycol. RESULTS: The basic characteristics of the present method were found to be satisfactory to determine the redox status of serum apoE quantitatively. Serum apoE was separated into its reduced-form (r-), non-reduced-form (nr-), apoE-AII complex, and homodimer using this method. R-apoE could be detected as a 40-kDa band, whereas nr-apoE remained as monomeric apoE. R-apoE displayed a preference for VLDL; however, the levels showed the correlation with HDL-cholesterol levels (p<0.005). Redox status of serum apoE was significantly different among apoE phenotypes. The quantitative ratios of nr-apoE to total apoE in serum from subjects with apoE4/E3 were higher than in serum from subjects with apoE3/E3 (p<0.0001) and apoE3/E2 (p<0.001). CONCLUSION: The redox status of serum apoE might be related to the synthesis of HDL. The information concerning the redox status of serum apoE provided by the present method may be a potent indicator to evaluate various apoE-related diseases.
[Mh] Termos MeSH primário: Apolipoproteínas E/sangue
HDL-Colesterol/sangue
[Mh] Termos MeSH secundário: Apolipoproteína A-II/sangue
Apolipoproteína A-II/química
Apolipoproteína A-II/isolamento & purificação
Apolipoproteína E2/sangue
Apolipoproteína E2/química
Apolipoproteína E2/isolamento & purificação
Apolipoproteína E3/sangue
Apolipoproteína E3/química
Apolipoproteína E3/isolamento & purificação
Apolipoproteína E4/sangue
Apolipoproteína E4/química
Apolipoproteína E4/isolamento & purificação
Apolipoproteínas E/química
Apolipoproteínas E/isolamento & purificação
HDL-Colesterol/química
Cisteína/química
Diamida/química
Dimerização
Ditiotreitol/química
Ensaio de Desvio de Mobilidade Eletroforética
Células HEK293
Seres Humanos
Indicadores e Reagentes/química
Peso Molecular
Oxirredução
Processos Fotoquímicos
Polietilenoglicóis/química
Solubilidade
Reagentes de Sulfidrila/química
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apolipoprotein A-II); 0 (Apolipoprotein E2); 0 (Apolipoprotein E3); 0 (Apolipoprotein E4); 0 (Apolipoproteins E); 0 (Cholesterol, HDL); 0 (Indicators and Reagents); 0 (Sulfhydryl Reagents); 0 (apo E-apo A-II complex); 10465-78-8 (Diamide); 30IQX730WE (Polyethylene Glycols); K848JZ4886 (Cysteine); T8ID5YZU6Y (Dithiothreitol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE


  6 / 4080 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28246333
[Au] Autor:Yoshida K; Hisabori T
[Ad] Endereço:Laboratory for Chemistry and Life Science, Tokyo Institute of Technology, Nagatsuta 4259-R1-8, Midori-ku, Yokohama 226-8503, Japan yoshida.k.ao@m.titech.ac.jp thisabor@res.titech.ac.jp.
[Ti] Título:Distinct electron transfer from ferredoxin-thioredoxin reductase to multiple thioredoxin isoforms in chloroplasts.
[So] Source:Biochem J;474(8):1347-1360, 2017 Apr 04.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Thiol-based redox regulation is considered to support light-responsive control of various chloroplast functions. The redox cascade via ferredoxin-thioredoxin reductase (FTR)/thioredoxin (Trx) has been recognized as a key to transmitting reducing power; however, genome sequencing has revealed that as many as five Trx subtypes encoded by a total of 10 nuclear genes are targeted to chloroplasts. Because each Trx isoform seems to have a distinct target selectivity, the electron distribution from FTR to multiple Trxs is thought to be the critical branch point for determining the consequence of chloroplast redox regulation. In the present study, we aimed to comprehensively characterize the kinetics of electron transfer from FTR to 10 Trx isoforms. We prepared the recombinant FTR protein from in the heterodimeric form containing the Fe-S cluster. By reconstituting the FTR/Trx system , we showed that FTR prepared here was enzymatically active and suitable for uncovering biochemical features of chloroplast redox regulation. A series of redox state determinations using the thiol-modifying reagent, 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonate, indicated that all chloroplast Trx isoforms are commonly reduced by FTR; however, significantly different efficiencies were evident. These differences were apparently correlated with the distinct midpoint redox potentials among Trxs. Even when the experiments were performed under conditions of hypothetical stoichiometry of FTR and Trxs, a similar trend in distinguishable electron transfers was observed. These data highlight an aspect of highly organized circuits in the chloroplast redox regulation network.
[Mh] Termos MeSH primário: Proteínas de Arabidopsis/metabolismo
Tiorredoxinas de Cloroplastos/metabolismo
Cloroplastos/metabolismo
Transporte de Elétrons
Proteínas com Ferro-Enxofre/metabolismo
Modelos Moleculares
Oxirredutases/metabolismo
[Mh] Termos MeSH secundário: Arabidopsis/enzimologia
Arabidopsis/metabolismo
Proteínas de Arabidopsis/química
Proteínas de Arabidopsis/genética
Biocatálise/efeitos dos fármacos
Domínio Catalítico
Tiorredoxinas de Cloroplastos/química
Tiorredoxinas de Cloroplastos/genética
Cloroplastos/enzimologia
Transporte de Elétrons/efeitos dos fármacos
Proteínas com Ferro-Enxofre/química
Proteínas com Ferro-Enxofre/genética
Oxirredução
Oxirredutases/química
Oxirredutases/genética
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
Isoformas de Proteínas/química
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Subunidades Proteicas/química
Subunidades Proteicas/genética
Subunidades Proteicas/metabolismo
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Estilbenos/farmacologia
Reagentes de Sulfidrila/farmacologia
Ácidos Sulfônicos/farmacologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-acetamido-4'-maleimidylstilbene-2,2'-disulfonate); 0 (Arabidopsis Proteins); 0 (Chloroplast Thioredoxins); 0 (Iron-Sulfur Proteins); 0 (Peptide Fragments); 0 (Protein Isoforms); 0 (Protein Subunits); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 0 (Stilbenes); 0 (Sulfhydryl Reagents); 0 (Sulfonic Acids); 0 (TRX m4 protein, Arabidopsis); EC 1.- (Oxidoreductases); EC 1.18.- (ferredoxin-thioredoxin reductase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170516
[Lr] Data última revisão:
170516
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170302
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20161089


  7 / 4080 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26494474
[Au] Autor:Tsai CW; Yang MD; Hsia TC; Chang WS; Hsu CM; Hsieh YH; Chung JG; Bau DT
[Ad] Endereço:Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan.
[Ti] Título:Dithiothreitol enhanced arsenic-trioxide-induced cell apoptosis in cultured oral cancer cells via mitochondrial dysfunction and endoplasmic reticulum stress.
[So] Source:Environ Toxicol;32(1):17-27, 2017 Jan.
[Is] ISSN:1522-7278
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Arsenic is naturally occurring toxic metalloid and drinking As O containing water are recognized to be related to increased risk of neurotoxicity, liver injury, blackfoot disease, hypertension, and cancer. On the contrary, As O has been an ancient drug used in traditional Chinese medicine with substantial anticancer activities, especially in the treatment of acute promyelocytic leukemia as well as chronic wound healing. However, the cytotoxicity and detail mechanisms of As O action in solid cancer cells, such as oral cancer cells, are largely unknown. In this study, we have primarily cultured four pairs of tumor and nontumor cells from the oral cancer patients and treated the cells with As O alone or combined with dithiothreitol (DTT). The results showed that 0.5 µM As O plus 20 µM DTT caused a significant cell death of oral cancer cells but not the nontumor cells. Also As O plus DTT upregulated Bax and Bak, downregulated Bcl-2 and p53, caused a loss of mitochondria membrane potential in oral cancer cells. On the other way, As O also triggered endoplasmic reticulum stress and increased the levels of glucose-regulated protein 78, calpain 1 and 2. Our results suggest that DTT could synergistically enhance the effects of As O on killing oral cancer cells while nontoxic to the nontumor cells. The combination is promising for clinical practice in oral cancer therapy and worth further investigations. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 17-27, 2017.
[Mh] Termos MeSH primário: Antineoplásicos/toxicidade
Apoptose/efeitos dos fármacos
Ditiotreitol/farmacologia
Estresse do Retículo Endoplasmático/efeitos dos fármacos
Doenças Mitocondriais/induzido quimicamente
Neoplasias Bucais/tratamento farmacológico
Óxidos/toxicidade
Reagentes de Sulfidrila/farmacologia
[Mh] Termos MeSH secundário: Arsenicais
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Ensaio Cometa
Dano ao DNA
Sinergismo Farmacológico
Seres Humanos
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Doenças Mitocondriais/metabolismo
Doenças Mitocondriais/patologia
Neoplasias Bucais/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Arsenicals); 0 (Oxides); 0 (Sulfhydryl Reagents); S7V92P67HO (arsenic trioxide); T8ID5YZU6Y (Dithiothreitol)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151024
[St] Status:MEDLINE
[do] DOI:10.1002/tox.22208


  8 / 4080 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:27898047
[Au] Autor:Díaz-Sánchez ÁG; Alvarez-Parrilla E; Martínez-Martínez A; Aguirre-Reyes L; Orozpe-Olvera JA; Ramos-Soto MA; Núñez-Gastélum JA; Alvarado-Tenorio B; de la Rosa LA
[Ad] Endereço:Departamento de Ciencias Químico-Biológicas, Instituto de Ciencias Biomédicas, Universidad Autónoma de Ciudad Juárez, Ciudad Juárez, Chihuahua 32310, Mexico. angel.diaz@uacj.mx.
[Ti] Título:Inhibition of Urease by Disulfiram, an FDA-Approved Thiol Reagent Used in Humans.
[So] Source:Molecules;21(12), 2016 Nov 26.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Urease is a nickel-dependent amidohydrolase that catalyses the decomposition of urea into carbamate and ammonia, a reaction that constitutes an important source of nitrogen for bacteria, fungi and plants. It is recognized as a potential antimicrobial target with an impact on medicine, agriculture, and the environment. The list of possible urease inhibitors is continuously increasing, with a special interest in those that interact with and block the flexible active site flap. We show that disulfiram inhibits urease in (CVU), following a non-competitive mechanism, and may be one of this kind of inhibitors. Disulfiram is a well-known thiol reagent that has been approved by the FDA for treatment of chronic alcoholism. We also found that other thiol reactive compounds (l-captopril and Bithionol) and quercetin inhibits CVU. These inhibitors protect the enzyme against its full inactivation by the thiol-specific reagent Aldrithiol (2,2'-dipyridyl disulphide, DPS), suggesting that the three drugs bind to the same subsite. Enzyme kinetics, competing inhibition experiments, auto-fluorescence binding experiments, and docking suggest that the disulfiram reactive site is Cys592, which has been proposed as a "hinge" located in the flexible active site flap. This study presents the basis for the use of disulfiram as one potential inhibitor to control urease activity.
[Mh] Termos MeSH primário: Dissulfiram/farmacologia
Inibidores Enzimáticos/farmacologia
Reagentes de Sulfidrila/farmacologia
Urease/antagonistas & inibidores
[Mh] Termos MeSH secundário: Aprovação de Drogas/legislação & jurisprudência
Cinética
Estados Unidos
United States Food and Drug Administration
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Sulfhydryl Reagents); EC 3.5.1.5 (Urease); TR3MLJ1UAI (Disulfiram)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161130
[St] Status:MEDLINE


  9 / 4080 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27685835
[Au] Autor:Bocedi A; Fabrini R; Pedersen JZ; Federici G; Iavarone F; Martelli C; Castagnola M; Ricci G
[Ad] Endereço:Department of Chemical Sciences and Technologies, University of Rome 'Tor Vergata', Italy.
[Ti] Título:The extreme hyper-reactivity of selected cysteines drives hierarchical disulfide bond formation in serum albumin.
[So] Source:FEBS J;283(22):4113-4127, 2016 Nov.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:After mild reduction of serum albumin, seven among the 34 cysteines forming the disulfide network displayed a surprising hyper-reactivity. Compared to the thiol group of glutathione, the average reactivity of these cysteines towards disulfides and thiol reagents was more than 100 times higher. Using mass spectrometry and kinetic data, we identified all these unusual residues, with Cys75, Cys123 and Cys264 showing the highest reactivity. This effect was mainly due to a low pK of the sulfhydryl groups and may explain the very fast formation of early disulfides in the nascent protein suggesting the existence of a hierarchical propensity to form such covalent links in selected regions during oxidative folding. An identical pattern of hyper-reactive cysteines was found in albumins from six different mammals. This hyper-reactivity is much higher than the one found in other proteins containing multiple cysteines only devoted to structural disulfide bonds. It is possible that such hyper-reactive cysteines could also be present in other proteins, although their existence has been completely ignored so far.
[Mh] Termos MeSH primário: Cisteína/química
Dissulfetos/química
Albumina Sérica/química
Reagentes de Sulfidrila/química
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Bovinos
Cisteína/metabolismo
Dissulfetos/metabolismo
Cães
Glutationa/química
Glutationa/metabolismo
Cabras
Cavalos
Seres Humanos
Cinética
Modelos Moleculares
Domínios Proteicos
Dobramento de Proteína
Albumina Sérica/metabolismo
Ovinos
Especificidade da Espécie
Compostos de Sulfidrila/química
Compostos de Sulfidrila/metabolismo
Reagentes de Sulfidrila/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Disulfides); 0 (Serum Albumin); 0 (Sulfhydryl Compounds); 0 (Sulfhydryl Reagents); GAN16C9B8O (Glutathione); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160930
[St] Status:MEDLINE
[do] DOI:10.1111/febs.13909


  10 / 4080 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
[PMID]:27602944
[Au] Autor:Kantner T; Watts AG
[Ad] Endereço:Department of Pharmacy and Pharmacology, University of Bath , Claverton Down, Bath BA2 7AY, United Kingdom.
[Ti] Título:Characterization of Reactions between Water-Soluble Trialkylphosphines and Thiol Alkylating Reagents: Implications for Protein-Conjugation Reactions.
[So] Source:Bioconjug Chem;27(10):2400-2406, 2016 Oct 19.
[Is] ISSN:1520-4812
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Water-soluble trialkylphosphines such as tris(carboxyethyl)phosphine (TCEP) and trishydroxypropyl phosphine (THPP) are effective agents for reducing disulfide bonds in proteins and are increasingly becoming the reagents of choice for bioconjugation strategies that modify cysteine (thiol containing) amino acids. These reducing agents are often considered as being chemically compatible with Michael acceptors such as maleimides and, as such, are often not removed prior to performing protein conjugation reactions. Here, we demonstrate the rapid and irreversible reaction of both TCEP and THPP with derivatives of the commonly employed thiol alkylating groups, maleimide and vinyl sulfone. Mechanistic investigations revealed distinct differences between the reactions of TCEP and THPP with maleimide, leading to the production of either nonproductive ylenes or succidimidyl derivatives, respectively. Importantly, we also demonstrate the incorporation of nonproductive ylenes formed between maleimide and TCEP into the Pneumococcal capsular polysaccharide Pn6b following strategies employed toward the production of conjugate vaccines.
[Mh] Termos MeSH primário: Fosfinas/química
Proteínas/química
[Mh] Termos MeSH secundário: Alquilantes/química
Dissulfetos/química
Espectroscopia de Ressonância Magnética
Maleimidas/química
Polissacarídeos/química
Solubilidade
Reagentes de Sulfidrila/química
Sulfonas/química
Água
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkylating Agents); 0 (Disulfides); 0 (Maleimides); 0 (Phosphines); 0 (Polysaccharides); 0 (Proteins); 0 (Sulfhydryl Reagents); 0 (Sulfones); 059QF0KO0R (Water); 22OAC2MO2S (tris(2-carboxyethyl)phosphine); 2519R1UGP8 (maleimide); 31973457VY (phenyl vinyl sulfone)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160908
[St] Status:MEDLINE



página 1 de 408 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde