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[PMID]:28451837
[Au] Autor:Cao W; Li H; Luo J; Yin J; Wan Y
[Ad] Endereço:State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, People's Republic of China.
[Ti] Título:High-level productivity of α,ω-dodecanedioic acid with a newly isolated Candida viswanathii strain.
[So] Source:J Ind Microbiol Biotechnol;44(8):1191-1202, 2017 Aug.
[Is] ISSN:1476-5535
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:α,ω-Dicarboxylic acids (DC) are versatile chemical intermediates with different chain lengths, which are well-known as polymer building block. In this work, a new strain with high productivity of DC was isolated from oil-contaminated soil. Based on the morphology and phylogenetic analyses of the internal transcribed spacer sequences, it was characterized as Candida viswanathii. It was found that the contribution of carbon flux to the cell growth and DC production from n-dodecane could be regulated by the sucrose and yeast extract concentrations in the medium, and besides the broth pH, a suitable proportioning of sucrose and yeast extract was the key to achieve the optimal transition from cell growth phase to DC production phase. By optimizing culture conditions in a 7.5-L bioreactor, a higher DC productivity of 1.59 g·L h with a corresponding concentration of 181.6 g/L was obtained. After the purification of DC from the culture, the results from gas chromatography-mass spectrometry, infrared spectroscopy and H-NMR showed that α,ω-dodecanedioic acid (DC ) was the major product of C. viswanathii ipe-1 using pure n-dodecane as substrate. For the first time, we reported that a high productivity of DC could be produced by C. viswanathii.
[Mh] Termos MeSH primário: Candida/metabolismo
Ácidos Dicarboxílicos/metabolismo
[Mh] Termos MeSH secundário: Alcanos/química
Reatores Biológicos
Candida/classificação
Meios de Cultura/química
Cromatografia Gasosa-Espectrometria de Massas
Concentração de Íons de Hidrogênio
Filogenia
Sacarose/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkanes); 0 (Culture Media); 0 (Dicarboxylic Acids); 11A386X1QH (n-dodecane); 57-50-1 (Sucrose); 978YU42Q6I (dodecanedioic acid)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1007/s10295-017-1948-6


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[PMID]:28867713
[Au] Autor:Amino Y; Nishi S; Izawa K
[Ad] Endereço:Institute for Innovation, Ajinomoto Co., Inc.
[Ti] Título:Stereo-Selective Preparation of Teneraic Acid, trans-(2S,6S)-Piperidine-2,6-dicarboxylic Acid, via Anodic Oxidation and Cobalt-Catalyzed Carbonylation.
[So] Source:Chem Pharm Bull (Tokyo);65(9):854-861, 2017.
[Is] ISSN:1347-5223
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Teneraic acid (piperidine-2,6-dicarboxylic acid) is a naturally occurring imino acid that comprises three stereoisomers due to its two asymmetric centers at C2 and C6. The configuration of natural teneraic acid is reported to correspond to trans-(2S,6S). However, a few studies are focused on the stereospecific synthesis of trans-(2S,6S)-teneraic acid. The present study investigates a convenient synthetic method that includes regiospecific anodic oxidation and stereospecific cobalt-catalyzed carbonylation to obtain trans-(2S,6S)-teneraic acid. Methyl (S)-N-benzoyl-α-methoxypipecolate, the key intermediate that displays a structure that corresponds to an intermediate (N-α-hydroxyalkyl amide) of intramolecular amidocarbonylation, was obtained via an anodic oxidation of methyl (S)-N-benzoylpipecolate. Subsequently, cobalt-catalyzed carbonylation converted the methyl (S)-N-benzoyl-α-methoxypipecolate to trans-(2S,6S)-N-benzoyl-teneraic acid dimethyl ester in good optical purity (>95% enantiomeric excess (ee)) and modest yield (63%). Finally, de-protection occurred via acidic hydrolysis to obtain trans-(2S,6S)-teneraic acid. The stereochemistry of synthesized teneraic acid was confirmed as corresponding to trans-(2S,6S) by comparing its physical properties with those of a cis-meso-isomer and those of a trans-(2S,6S)-isomer that were reported in previous studies.
[Mh] Termos MeSH primário: Cobalto/química
Ácidos Dicarboxílicos/química
Piperidinas/química
[Mh] Termos MeSH secundário: Aldeídos/química
Amidas/química
Catálise
Dicroísmo Circular
Ácidos Dicarboxílicos/síntese química
Oxirredução
Estereoisomerismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aldehydes); 0 (Amides); 0 (Dicarboxylic Acids); 0 (Piperidines); 3G0H8C9362 (Cobalt)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE
[do] DOI:10.1248/cpb.c17-00391


  3 / 3239 MEDLINE  
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[PMID]:28726106
[Au] Autor:Lebedev DS; Ivanov IA; Kryukova EV; Starkov VG; Tsetlin VI; Utkin YN
[Ad] Endereço:Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia. dmitry-1@bk.ru.
[Ti] Título:Arginine derivatives of dicarboxylic acids from the parotid gland secretions of common toad Bufo bufo-New agonists of ionotropic γ-aminobutyric acid receptors.
[So] Source:Dokl Biochem Biophys;474(1):178-182, 2017 May.
[Is] ISSN:1608-3091
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:Compounds activating γ-aminobutyric acid type A receptor were isolated from the toad Bufo bufo venom as a result of chromatographic separation. Analysis of the structure of these compounds by mass spectrometry and nuclear magnetic resonance showed that they are arginine derivatives of dicarboxylic acids and represent suberylarginine, pimeloylarginine, and adipoylarginine.
[Mh] Termos MeSH primário: Arginina/química
Bufo bufo
Ácidos Dicarboxílicos/química
Ácidos Dicarboxílicos/farmacologia
Agonistas de Receptores de GABA-A/química
Agonistas de Receptores de GABA-A/farmacologia
Glândula Parótida/secreção
Receptores de GABA-A/metabolismo
[Mh] Termos MeSH secundário: Animais
Ácidos Dicarboxílicos/metabolismo
Agonistas de Receptores de GABA-A/metabolismo
Células HEK293
Seres Humanos
Ligantes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dicarboxylic Acids); 0 (GABA-A Receptor Agonists); 0 (Ligands); 0 (Receptors, GABA-A); 94ZLA3W45F (Arginine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1134/S1607672917030127


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[PMID]:28662387
[Au] Autor:Cao W; Liu B; Luo J; Yin J; Wan Y
[Ad] Endereço:State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
[Ti] Título:α, ω-Dodecanedioic acid production by Candida viswanathii ipe-1 with co-utilization of wheat straw hydrolysates and n-dodecane.
[So] Source:Bioresour Technol;243:179-187, 2017 Nov.
[Is] ISSN:1873-2976
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Candida viswanathii ipe-1 was used to produce α, ω-dodecanedioic acid (DC ), which showed capability to ferment xylose and glucose simultaneously, while arabinose utilization was less efficient. A low concentration of furfural enhanced cell growth, and the addition of 4.0g/L sodium acetate largely increased DC production. It indicated that detoxification of the wheat straw hydrolysates was not necessary for the biosynthesis of DC . Based on the promising features of our strain, an efficient process was developed to produce DC from co-utilization of wheat straw hydrolysates and n-dodecane. Using this process, 129.7g/L DC with a corresponding productivity of 1.13g·L ·h could be produced, which was increased by 40.0% compared with a sole carbon of glucose. The improved DC yield by the co-utilization of wheat straw hydrolysates and n-dodecane using C. viswanathii ipe-1 demonstrates the great potential of using biomass as a feedstock in the production of DC .
[Mh] Termos MeSH primário: Candida
Ácidos Dicarboxílicos
Triticum
[Mh] Termos MeSH secundário: Alcanos
Fermentação
Hidrólise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkanes); 0 (Dicarboxylic Acids); 11A386X1QH (n-dodecane); 978YU42Q6I (dodecanedioic acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE


  5 / 3239 MEDLINE  
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[PMID]:28637458
[Au] Autor:Marie C; Hamlaoui S; Bernard L; Bourdeaux D; Sautou V; Lémery D; Vendittelli F; Sauvant-Rochat MP
[Ad] Endereço:Axe TGI-PEPRADE, Institut Pascal, Sigma Clermont, CNRS, Université Clermont Auvergne, 63001, Clermont-Ferrand, France. cmarie@chu-clermontferrand.fr.
[Ti] Título:Exposure of hospitalised pregnant women to plasticizers contained in medical devices.
[So] Source:BMC Womens Health;17(1):45, 2017 Jun 20.
[Is] ISSN:1472-6874
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Medical devices (MDs) in polyvinyl chloride (PVC) are not a well-known source of exposure to plasticizers, in particular during pregnancy. Because of its toxicity, the di-(2-ethylhexyl) phthalate (DEHP) has been replaced by other plasticizers such as di (isononyl)-cyclohexane-1,2-dicarboxilic acid (DINCH), tri-octyltrimellitate (TOTM) and di-(isononyl) phthalate (DiNP). Our study aimed to quantify the plasticizers (DEHP and alternative plasticizers) contained in PVC medical devices used for hospitalised pregnant women and to describe which these MDs had been used (type, number, duration of exposure). METHODS: The plasticizers contained in the MDs used for daily care in the Obstetrics Department of a French University Hospital were extracted from PVC (after contact with a chloroform solution), identified and quantified by gas-chromatography-mass-spectrometry analysis. A total of 168 pregnant women hospitalised in the Obstetrics Department with at least one catheter were included in the observational study. The median number of MDs containing plasticizers used and the daily duration of exposure to the MDs were compared in three groups of pregnant women: "Pathology group" (women hospitalised for an obstetric disorder who did not give birth during this hospitalisation; n = 52), "Pathology and delivery group" (hospitalised for an obstetric disorder and who gave birth during this stay; n = 23) and "Delivery group" (admitted for planned or spontaneous delivery without obstetric disorder; n = 93). RESULTS: DiNP, TOTM and DINCH were the predominant plasticizers contained in the MDs at an amount of 29 to 36 g per 100 g of PVC. Women in the "Pathology group" (preterm labour or other pathology) were exposed to a median number of two MDs containing TOTM and one MD containing DiNP, fewer than those in the "Pathology and delivery group" (p < 0.05). Women in the "Pathology group" had a median exposure of 3.4 h/day to MDs containing DiNP and 8.2 h/day to MDs containing TOTM, longer than those in the "Delivery group" (p < 0.01). CONCLUSIONS: Our study shows that the medical management of pregnant women in a hospital setting entails exposure to MDs containing alternative plasticizers (DiNP, TOTM and DINCH).
[Mh] Termos MeSH primário: Equipamentos e Provisões
Hospitalização
Exposição Materna
Plastificantes/análise
Cloreto de Polivinila/análise
[Mh] Termos MeSH secundário: Adulto
Benzoatos/análise
Ácidos Cicloexanocarboxílicos/análise
Ácidos Dicarboxílicos/análise
Feminino
Seres Humanos
Ácidos Ftálicos/análise
Gravidez
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Benzoates); 0 (Cyclohexanecarboxylic Acids); 0 (Dicarboxylic Acids); 0 (Phthalic Acids); 0 (Plasticizers); 0 (diisononyl 1,2-cyclohexanedicarboxylic acid); 6O7F7IX66E (phthalic acid); 9002-86-2 (Polyvinyl Chloride); 9GPJ04URH3 (trioctyl trimellitate)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170815
[Lr] Data última revisão:
170815
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.1186/s12905-017-0398-7


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[PMID]:28632393
[Au] Autor:Hsu HC; Tong S; Zhou Y; Elmes MW; Yan S; Kaczocha M; Deutsch DG; Rizzo RC; Ojima I; Li H
[Ad] Endereço:Cryo-EM Structural Biology Laboratory, Van Andel Research Institute , Grand Rapids, Michigan 49503, United States.
[Ti] Título:The Antinociceptive Agent SBFI-26 Binds to Anandamide Transporters FABP5 and FABP7 at Two Different Sites.
[So] Source:Biochemistry;56(27):3454-3462, 2017 Jul 11.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human FABP5 and FABP7 are intracellular endocannabinoid transporters. SBFI-26 is an α-truxillic acid 1-naphthyl monoester that competitively inhibits the activities of FABP5 and FABP7 and produces antinociceptive and anti-inflammatory effects in mice. The synthesis of SBFI-26 yields several stereoisomers, and it is not known how the inhibitor binds the transporters. Here we report co-crystal structures of SBFI-26 in complex with human FABP5 and FABP7 at 2.2 and 1.9 Å resolution, respectively. We found that only (S)-SBFI-26 was present in the crystal structures. The inhibitor largely mimics the fatty acid binding pattern, but it also has several unique interactions. Notably, the FABP7 complex corroborates key aspects of the ligand binding pose at the canonical site previously predicted by virtual screening. In FABP5, SBFI-26 was unexpectedly found to bind at the substrate entry portal region in addition to binding at the canonical ligand-binding pocket. Our structural and binding energy analyses indicate that both R and S forms appear to bind the transporter equally well. We suggest that the S enantiomer observed in the crystal structures may be a result of the crystallization process selectively incorporating the (S)-SBFI-26-FABP complexes into the growing lattice, or that the S enantiomer may bind to the portal site more rapidly than to the canonical site, leading to an increased local concentration of the S enantiomer for binding to the canonical site. Our work reveals two binding poses of SBFI-26 in its target transporters. This knowledge will guide the development of more potent FABP inhibitors based upon the SBFI-26 scaffold.
[Mh] Termos MeSH primário: Analgésicos/metabolismo
Ciclobutanos/metabolismo
Ácidos Dicarboxílicos/metabolismo
Proteína 7 de Ligação a Ácidos Graxos/metabolismo
Proteínas de Ligação a Ácido Graxo/metabolismo
Modelos Moleculares
Proteínas Supressoras de Tumor/metabolismo
[Mh] Termos MeSH secundário: Analgésicos/química
Analgésicos/farmacologia
Animais
Anti-Inflamatórios não Esteroides/química
Anti-Inflamatórios não Esteroides/metabolismo
Anti-Inflamatórios não Esteroides/farmacologia
Apoproteínas/antagonistas & inibidores
Apoproteínas/química
Apoproteínas/genética
Apoproteínas/metabolismo
Sítios de Ligação
Domínio Catalítico
Biologia Computacional
Cristalografia por Raios X
Ciclobutanos/química
Ciclobutanos/farmacologia
Ácidos Dicarboxílicos/química
Ácidos Dicarboxílicos/farmacologia
Proteína 7 de Ligação a Ácidos Graxos/antagonistas & inibidores
Proteína 7 de Ligação a Ácidos Graxos/química
Proteína 7 de Ligação a Ácidos Graxos/genética
Proteínas de Ligação a Ácido Graxo/antagonistas & inibidores
Proteínas de Ligação a Ácido Graxo/química
Proteínas de Ligação a Ácido Graxo/genética
Seres Humanos
Ligantes
Camundongos
Conformação Molecular
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
Conformação Proteica
Proteínas Recombinantes
Estereoisomerismo
Proteínas Supressoras de Tumor/antagonistas & inibidores
Proteínas Supressoras de Tumor/química
Proteínas Supressoras de Tumor/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-naphthyl alpha-truxillate); 0 (Analgesics); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Apoproteins); 0 (Cyclobutanes); 0 (Dicarboxylic Acids); 0 (FABP5 protein, human); 0 (FABP7 protein, human); 0 (Fatty Acid-Binding Protein 7); 0 (Fatty Acid-Binding Proteins); 0 (Ligands); 0 (Recombinant Proteins); 0 (Tumor Suppressor Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00194


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[PMID]:28398653
[Au] Autor:Lavaur J; Le Nogue D; Lemaire M; Pype J; Farjot G; Hirsch EC; Michel PP
[Ad] Endereço:Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle épinière (ICM), Hôpital Pitié-Salpêtrière, Paris, France.
[Ti] Título:The noble gas xenon provides protection and trophic stimulation to midbrain dopamine neurons.
[So] Source:J Neurochem;142(1):14-28, 2017 Jul.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Despite its low chemical reactivity, the noble gas xenon possesses a remarkable spectrum of biological effects. In particular, xenon is a strong neuroprotectant in preclinical models of hypoxic-ischemic brain injury. In this study, we wished to determine whether xenon retained its neuroprotective potential in experimental settings that model the progressive loss of midbrain dopamine (DA) neurons in Parkinson's disease. Using rat midbrain cultures, we established that xenon was partially protective for DA neurons through either direct or indirect effects on these neurons. So, when DA neurons were exposed to l-trans-pyrrolidine-2,4-dicarboxylic acid so as to increase ambient glutamate levels and generate slow and sustained excitotoxicity, the effect of xenon on DA neurons was direct. The vitamin E analog Trolox also partially rescued DA neurons in this setting and enhanced neuroprotection by xenon. However, in the situation where DA cell death was spontaneous, the protection of DA neurons by xenon appeared indirect as it occurred through the repression of a mechanism mediated by proliferating glial cells, presumably astrocytes and their precursor cells. Xenon also exerted trophic effects for DA neurons in this paradigm. The effects of xenon were mimicked and improved by the N-methyl-d-aspartate glutamate receptor antagonist memantine and xenon itself appeared to work by antagonizing N-methyl-d-aspartate receptors. Note that another noble gas argon could not reproduce xenon effects. Overall, present data indicate that xenon can provide protection and trophic support to DA neurons that are vulnerable in Parkinson's disease. This suggests that xenon might have some therapeutic value for this disorder.
[Mh] Termos MeSH primário: Anestésicos Inalatórios/farmacologia
Neurônios Dopaminérgicos/efeitos dos fármacos
Mesencéfalo/efeitos dos fármacos
Fármacos Neuroprotetores/farmacologia
Xenônio/farmacologia
[Mh] Termos MeSH secundário: Animais
Antioxidantes/farmacologia
Morte Celular/efeitos dos fármacos
Células Cultivadas
Cromanos/farmacologia
Ácidos Dicarboxílicos/antagonistas & inibidores
Ácidos Dicarboxílicos/toxicidade
Antagonistas de Aminoácidos Excitatórios/farmacologia
Memantina/farmacologia
Técnicas de Cultura de Órgãos
Pirrolidinas/antagonistas & inibidores
Pirrolidinas/toxicidade
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anesthetics, Inhalation); 0 (Antioxidants); 0 (Chromans); 0 (Dicarboxylic Acids); 0 (Excitatory Amino Acid Antagonists); 0 (Neuroprotective Agents); 0 (Pyrrolidines); 3H3U766W84 (Xenon); 99319-03-6 (pyrrolidine-2,4-dicarboxylic acid); S18UL9710X (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid); W8O17SJF3T (Memantine)
[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:170412
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.14041


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[PMID]:28351588
[Au] Autor:Agarwal HK; Chhikara BS; Doncel GF; Parang K
[Ad] Endereço:School of Pharmacy, South University, 10 Science Court, Columbia, SC 29203, United States.
[Ti] Título:Synthesis and anti-HIV activities of unsymmetrical long chain dicarboxylate esters of dinucleoside reverse transcriptase inhibitors.
[So] Source:Bioorg Med Chem Lett;27(9):1934-1937, 2017 05 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of 11 unsymmetrical dicarboxylate conjugates of dinucleoside reverse transcriptase inhibitors were synthesized. Three dicarboxylic acids, succinic acid, suberic acid and 1,14-tetradecandioc acid, were diesterified with either 3'-azido-2',3'-dideoxythymidine (AZT), 3'-fluoro-2',3'-dideoxythymidine (FLT), 2',3'-dideoxy-3'-thiacytidine (3TC), or 5-fluoro-2',3'-dideoxy-3'-thiacytidine (FTC). The anti-HIV activity of synthesized compounds was evaluated against HIV-1 X4 (IIIB) and R5 (BaL) viral strains in single-round infection assays. Results indicated that the tetradecandioate esters of nucleosides were more active against HIV than the corresponding parent nucleosides and nucleoside conjugates. The tetradecandioate conjugate of FLT and FTC (5) was found to be the most potent compounds with EC values of 47 and 75nM against X4 and R5 HIV-1 strains, respectively, while the EC values for the parent analogs, FLT and FTC, ranged from 700 to 3300nM.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/química
Fármacos Anti-HIV/farmacologia
Transcriptase Reversa do HIV/antagonistas & inibidores
Nucleosídeos/química
Nucleosídeos/farmacologia
Inibidores da Transcriptase Reversa/química
Inibidores da Transcriptase Reversa/farmacologia
[Mh] Termos MeSH secundário: Fármacos Anti-HIV/síntese química
Ácidos Dicarboxílicos/síntese química
Ácidos Dicarboxílicos/química
Ácidos Dicarboxílicos/farmacologia
Ésteres/síntese química
Ésteres/química
Ésteres/farmacologia
Infecções por HIV/tratamento farmacológico
HIV-1/efeitos dos fármacos
Seres Humanos
Nucleosídeos/síntese química
Inibidores da Transcriptase Reversa/síntese química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Dicarboxylic Acids); 0 (Esters); 0 (Nucleosides); 0 (Reverse Transcriptase Inhibitors); EC 2.7.7.49 (HIV Reverse Transcriptase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171124
[Lr] Data última revisão:
171124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170330
[St] Status:MEDLINE


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[PMID]:28326944
[Au] Autor:Peng X; Studholme K; Kanjiya MP; Luk J; Bogdan D; Elmes MW; Carbonetti G; Tong S; Gary Teng YH; Rizzo RC; Li H; Deutsch DG; Ojima I; Rebecchi MJ; Puopolo M; Kaczocha M
[Ad] Endereço:1 Department of Anesthesiology, Stony Brook University, Stony Brook, NY, USA.
[Ti] Título:Fatty-acid-binding protein inhibition produces analgesic effects through peripheral and central mechanisms.
[So] Source:Mol Pain;13:1744806917697007, 2017 Jan.
[Is] ISSN:1744-8069
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background Fatty-acid-binding proteins (FABPs) are intracellular carriers for endocannabinoids, N-acylethanolamines, and related lipids. Previous work indicates that systemically administered FABP5 inhibitors produce analgesia in models of inflammatory pain. It is currently not known whether FABP inhibitors exert their effects through peripheral or central mechanisms. Here, we examined FABP5 distribution in dorsal root ganglia and spinal cord and examined the analgesic effects of peripherally and centrally administered FABP5 inhibitors. Results Immunofluorescence revealed robust expression of FABP5 in lumbar dorsal root ganglia. FABP5 was distributed in peptidergic calcitonin gene-related peptide-expressing dorsal root ganglia and non-peptidergic isolectin B4-expressing dorsal root ganglia. In addition, the majority of dorsal root ganglia expressing FABP5 also expressed transient receptor potential vanilloid 1 (TRPV1) and peripherin, a marker of nociceptive fibers. Intraplantar administration of FABP5 inhibitors reduced thermal and mechanical hyperalgesia in the complete Freund's adjuvant model of chronic inflammatory pain. In contrast to its robust expression in dorsal root ganglia, FABP5 was sparsely distributed in the lumbar spinal cord and intrathecal administration of FABP inhibitor did not confer analgesic effects. Administration of FABP inhibitor via the intracerebroventricular (i.c.v.) route reduced thermal hyperalgesia. Antagonists of peroxisome proliferator-activated receptor alpha blocked the analgesic effects of peripherally and i.c.v. administered FABP inhibitor while antagonism of cannabinoid receptor 1 blocked the effects of peripheral FABP inhibition and a TRPV1 antagonist blocked the effects of i.c.v. administered inhibitor. Although FABP5 and TRPV1 were co-expressed in the periaqueductal gray region of the brain, which is known to modulate pain, knockdown of FABP5 in the periaqueductal gray using adeno-associated viruses and pharmacological FABP5 inhibition did not produce analgesic effects. Conclusions This study demonstrates that FABP5 is highly expressed in nociceptive dorsal root ganglia neurons and FABP inhibitors exert peripheral and supraspinal analgesic effects. This indicates that peripherally restricted FABP inhibitors may serve as a new class of analgesic and anti-inflammatory agents.
[Mh] Termos MeSH primário: Analgésicos/uso terapêutico
Sistema Nervoso Central/metabolismo
Proteínas de Ligação a Ácido Graxo/metabolismo
Hiperalgesia/tratamento farmacológico
Proteínas de Neoplasias/metabolismo
Dor/tratamento farmacológico
Nervos Periféricos/metabolismo
[Mh] Termos MeSH secundário: Analgésicos/farmacologia
Animais
Ácidos Araquidônicos/metabolismo
Sistema Nervoso Central/efeitos dos fármacos
Ciclobutanos/uso terapêutico
Ácidos Dicarboxílicos/uso terapêutico
Modelos Animais de Doenças
Proteínas de Ligação a Ácido Graxo/genética
Adjuvante de Freund/toxicidade
Gânglios Espinais/metabolismo
Hiperalgesia/etiologia
Inflamação/induzido quimicamente
Inflamação/complicações
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Proteínas de Neoplasias/genética
Dor/complicações
Dor/etiologia
Limiar da Dor/efeitos dos fármacos
Nervos Periféricos/efeitos dos fármacos
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/metabolismo
Transdução Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-naphthyl alpha-truxillate); 0 (Analgesics); 0 (Arachidonic Acids); 0 (Cyclobutanes); 0 (Dicarboxylic Acids); 0 (Fabp5 protein, mouse); 0 (Fatty Acid-Binding Proteins); 0 (Neoplasm Proteins); 0 (RNA, Small Interfering); 9007-81-2 (Freund's Adjuvant)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.1177/1744806917697007


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[PMID]:28288640
[Au] Autor:Yang L; Christakou E; Vang J; Lübeck M; Lübeck PS
[Ad] Endereço:Section for Sustainable Biotechnology, Department of Chemistry and Bioscience, Aalborg University Copenhagen, A. C. Meyers Vænge 15, 2450, Copenhagen SV, Denmark.
[Ti] Título:Overexpression of a C -dicarboxylate transporter is the key for rerouting citric acid to C -dicarboxylic acid production in Aspergillus carbonarius.
[So] Source:Microb Cell Fact;16(1):43, 2017 Mar 14.
[Is] ISSN:1475-2859
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: C -dicarboxylic acids, including malic acid, fumaric acid and succinic acid, are valuable organic acids that can be produced and secreted by a number of microorganisms. Previous studies on organic acid production by Aspergillus carbonarius, which is capable of producing high amounts of citric acid from varieties carbon sources, have revealed its potential as a fungal cell factory. Earlier attempts to reroute citric acid production into C -dicarboxylic acids have been with limited success. RESULTS: In this study, a glucose oxidase deficient strain of A. carbonarius was used as the parental strain to overexpress a native C -dicarboxylate transporter and the gene frd encoding fumarate reductase from Trypanosoma brucei individually and in combination. Impacts of the introduced genetic modifications on organic acid production were investigated in a defined medium and in a hydrolysate of wheat straw containing high concentrations of glucose and xylose. In the defined medium, overexpression of the C -dicarboxylate transporter alone and in combination with the frd gene significantly increased the production of C -dicarboxylic acids and reduced the accumulation of citric acid, whereas expression of the frd gene alone did not result in any significant change of organic acid production profile. In the wheat straw hydrolysate after 9 days of cultivation, similar results were obtained as in the defined medium. High amounts of malic acid and succinic acid were produced by the same strains. CONCLUSIONS: This study demonstrates that the key to change the citric acid production into production of C -dicarboxylic acids in A. carbonarius is the C -dicarboxylate transporter. Furthermore it shows that the C -dicarboxylic acid production by A. carbonarius can be further increased via metabolic engineering and also shows the potential of A. carbonarius to utilize lignocellulosic biomass as substrates for C -dicarboxylic acid production.
[Mh] Termos MeSH primário: Aspergillus/genética
Aspergillus/metabolismo
Ácido Cítrico/metabolismo
Transportadores de Ácidos Dicarboxílicos/genética
Transportadores de Ácidos Dicarboxílicos/metabolismo
Ácidos Dicarboxílicos/metabolismo
Regulação para Cima
[Mh] Termos MeSH secundário: Biomassa
Meios de Cultura/química
Glucose/metabolismo
Glucose Oxidase/genética
Glucose Oxidase/metabolismo
Lignina/metabolismo
Malatos/metabolismo
Engenharia Metabólica/métodos
Polissacarídeos/metabolismo
Succinato Desidrogenase/genética
Triticum/metabolismo
Trypanosoma brucei brucei/enzimologia
Trypanosoma brucei brucei/genética
Xilose/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media); 0 (Dicarboxylic Acid Transporters); 0 (Dicarboxylic Acids); 0 (Malates); 0 (Polysaccharides); 11132-73-3 (lignocellulose); 2968PHW8QP (Citric Acid); 817L1N4CKP (malic acid); 9005-53-2 (Lignin); A1TA934AKO (Xylose); EC 1.1.3.4 (Glucose Oxidase); EC 1.3.99.1 (Succinate Dehydrogenase); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170420
[Lr] Data última revisão:
170420
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE
[do] DOI:10.1186/s12934-017-0660-6



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