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1.
Chem Commun (Camb) ; 55(89): 13458-13461, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31647069

RESUMO

Here, an enzyme mimic inspired by serine proteases was developed for the degradation of PAEs. This enzyme mimic, comprised an active site (SHD), a self-assembling polypeptide (LKLKLKL), a spacer (GGG) and a polymerizable site (DOPA) and showed high activity towards the degradation of DEHP in cells.


Assuntos
Dietilexilftalato/metabolismo , Ésteres/metabolismo , Ácidos Ftálicos/metabolismo , Serina Proteases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Dietilexilftalato/química , Dietilexilftalato/farmacologia , Ésteres/química , Ésteres/farmacologia , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Ácidos Ftálicos/química , Ácidos Ftálicos/farmacologia , Serina Proteases/química , Propriedades de Superfície , Temperatura Ambiente
2.
Chem Pharm Bull (Tokyo) ; 67(10): 1152-1159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582635

RESUMO

Melt adsorption is a manufacturing method that offers precise control of particle size distribution of granules and circumvents the disadvantages of conventional melt granulation. However, drug release from particles adsorbed with hydrophobic materials has not been fully investigated, and there are missing details as to whether particles manufactured by this technique can be applied to orally disintegrating tablets (ODT). In this report, we aimed to optimize process parameters and formulation to manufacture ODT containing melt adsorption-particles with the specific characteristic of sustained release. Melt adsorption particles containing Neusilin US2 as the adsorbent were prepared by using various waxes to determine the most suitable material for controlled release formulation. Glycerol fatty acid ester (Poem TR-FB: TR-FB) was the optimal wax examined because of its drug release pattern and tabletability. We then optimized manufacturing conditions by examining granulation time, disintegrant amount per tablet and compression force on the tablet for ODT that meet the criteria of controlled drug release, tensile strength and disintegration of the tablet. Multiple regression analysis revealed the effect of process parameters on tablet properties and drug release with increasing the granulation time affording sustained release of the drug. The analysis also showed that a high compression force crushed the granules coated by TR-FB, which impaired sustained drug release. From the regression model the optimal manufacturing conditions were determined, and the tablet prepared under these conditions concurred with the predicted values and met all criteria. This new technique should contribute to the development of ODT to improve medication adherence.


Assuntos
Compostos de Alumínio/química , Compostos de Magnésio/química , Silicatos/química , Administração Oral , Adsorção , Ésteres/química , Ácidos Graxos/química , Glicerol/química , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Propriedades de Superfície , Comprimidos/administração & dosagem , Comprimidos/química
3.
Chem Commun (Camb) ; 55(87): 13066-13069, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31570904

RESUMO

A platinum(ii) complex containing an aminophosphonate ligand preferentially accumulates in the endoplamic reticulum (ER) in association with potent ER stress and reactive oxygen species generation, followed by the activation of damage-associated molecular pattern signals and immune responses. Importantly, the Pt complex exhibits potent anti-tumour activities in two independent mouse models via an immunogenic cell death pathway.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Ésteres/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Organofosfonatos/farmacologia , Compostos Organoplatínicos/farmacologia , Animais , Antineoplásicos Imunológicos/química , Morte Celular/efeitos dos fármacos , Ésteres/química , Humanos , Ligantes , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Organofosfonatos/química , Compostos Organoplatínicos/química
4.
J Agric Food Chem ; 67(41): 11396-11402, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31537068

RESUMO

Phytase is commonly used as a feed enzyme in monogastric animals to increase the bioavailability of phytate phosphorus and other nutrients. The accumulation of myo-inositol phosphate intermediates during phytate degradation in various segments of the gastrointestinal tract (GIT) is poorly understood. The aim of this study was to determine the efficacy of Buttiauxella spp. phytase in degrading the phytate in corn, soybean meal, and complete corn-soybean meal diet to myo-inositol phosphate esters (IP1-IP5) and completely dephosphorylated myo-inositol rings using an in vitro model of the poultry upper GIT. Our results show that the phytase hydrolyzes phytate efficiently to small IP esters, whereas the myo-inositol level remains constant between control and phytase treatments. Although the in vitro digestion model does not incorporate all factors that govern phytate hydrolysis, it is a valuable tool for evaluating phytase efficacy at various enzyme doses and with different feed ingredients.


Assuntos
6-Fitase/química , Ração Animal/análise , Enterobacteriaceae/enzimologia , Ésteres/química , Fosfatos de Inositol/química , Ácido Fítico/química , 6-Fitase/metabolismo , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Galinhas , Digestão , Ésteres/metabolismo , Aditivos Alimentares/química , Aditivos Alimentares/metabolismo , Trato Gastrointestinal/metabolismo , Hidrólise , Fosfatos de Inositol/metabolismo , Modelos Biológicos , Ácido Fítico/metabolismo , Soja/química , Soja/metabolismo , Zea mays/química , Zea mays/metabolismo
5.
J Agric Food Chem ; 67(38): 10653-10659, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31464427

RESUMO

Quercetin, a polyphenolic compound, is widely distributed in plants and has numerous health benefits. However, its hydrophilicity can compromise its use in lipophilic systems. For this reason, quercetin was esterified with 12 different fatty acids as their acyl chlorides with varying chain lengths and degrees of unsaturation. Two monoesters (Q-3'-O-monoester and Q-3-O-monoester) and four diesters (Q-7,3'-O-diester, Q-3',4'-O-diester, Q-3,3'-O-diester, and Q-3,4'-O-diester) were the major products as was shown by HPLC-MS and 1H-NMR data. The lipophilicity of quercetin derivatives was calculated; this was found to increase with fatty acid chain length. The antioxidant potential of quercetin and its derivatives was evaluated by using DPPH radical and ABTS radical cation scavenging activity; quercetin showed the highest radical scavenging activity among all tested samples. Despite the decrease of antioxidant activity in this study, the derivatives may show better antioxidant activity in lipophilic media and display improved absorption and bioavailability in the body once consumed.


Assuntos
Antioxidantes/química , Ésteres/química , Quercetina/química , Antioxidantes/síntese química , Cromatografia Líquida de Alta Pressão , Esterificação , Ácidos Graxos/química , Espectrometria de Massas , Estrutura Molecular
6.
Chem Biol Interact ; 311: 108788, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31401088

RESUMO

Aqueous solutions of chlorpyrifos oxon are used to study the ability of chlorpyrifos oxon to catalyze protein crosslinking. Assays for protein crosslinking can avoid artifacts by using information on the stability of chlorpyrifos oxon in solution. We undertook to determine the half-life of chlorpyrifos oxon in aqueous solution because literature values do not exist. The rate of conversion of chlorpyrifos oxon to 3,5,6-trichloro-2-pyridinol was measured at 23 °C in 20 mM TrisCl pH 8 and pH 9 by recording loss of absorbance at 290 nm for chlorpyrifos oxon and increase in absorbance at 320 nm for 3,5,6-trichloro-2-pyridinol. The half-life of chlorpyrifos oxon was 20.9 days at pH 8 and 6.7 days at pH 9. Literature reports for the stability of other organophosphorus toxicants were summarized because our current studies suggest that other organophosphorus toxicants are also crosslinking agents.


Assuntos
Clorpirifos/análogos & derivados , Ésteres/química , Organofosfatos/química , Água/química , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Clorpirifos/química , Clorpirifos/metabolismo , Meia-Vida , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Organofosfatos/metabolismo , Hidróxido de Sódio/química , Espectrofotometria
7.
Eur J Med Chem ; 182: 111597, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31422225

RESUMO

Fatty acid synthase (FASN) is a lipogenic enzyme that is selectively upregulated in malignant cells. There is growing consensus on the oncogenicity of FASN-driven lipogenesis and the potential of FASN as a druggable target in cancer. Here, we report the synthesis and FASN inhibitory activities of two novel galloyl esters of trans-stilbene EC1 and EC5. Inhibition of FASN was accompanied by a loss in AKT activation and profound apoptosis in several non-small cell lung cancer (NSCLC) cells at the growth inhibitory concentrations of EC1 and EC5. Both FASN and phospho-AKT levels were concurrently downregulated. However, addition of a lipid concentrate to the treated cells reinstated cell viability and reversed the loss of FASN and AKT protein levels, thus recapitulating the causal relationship between FASN inhibition and the loss in cell viability.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ésteres/farmacologia , Ácido Graxo Sintase Tipo I/antagonistas & inibidores , Ácido Gálico/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Estilbenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ésteres/síntese química , Ésteres/química , Ácido Graxo Sintase Tipo I/metabolismo , Ácido Gálico/análogos & derivados , Ácido Gálico/química , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Estrutura Molecular , Estilbenos/síntese química , Estilbenos/química , Relação Estrutura-Atividade
8.
Food Chem ; 301: 125297, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31394336

RESUMO

Candida antarctica lipase B-catalysed synthesis of lipophilic esters of polydatin was investigated along with their antioxidant activities. The effects of synthesis parameters such as solvent, substrate molar ratio, enzyme concentration, addition of molecular sieves, reaction temperature and time on the production of ester were studied and optimised. The highest production of esters was obtained with acetone as the reaction solvent. The antioxidant activities of the esters were compared with those of commercial butylated hydroxytoluene (BHT) and α-tocopherol. All polydatin esters inhibited the oxidative destruction of ß-carotene more effectively than did BHT and α-tocopherol. Results of thiobarbituric acid tests showed that in bulk fish oil, all esters were more effective than α-tocopherol at 2 mmol/kg concentration but were not as effective as BHT. In fish oil-emulsions, all esters were more effective than both BHT and α-tocopherol at 2 mmol/kg concentration. The synthesized polydatin esters are promising antioxidants for oil/fat-based foods.


Assuntos
Antioxidantes/química , Emulsões/química , Óleos de Peixe/química , Glucosídeos/química , Estilbenos/química , Antioxidantes/farmacologia , Hidroxitolueno Butilado/farmacologia , Esterificação , Ésteres/química , Ácidos Graxos/química , Ácidos Graxos Ômega-3/química , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Lipase/química , Lipase/metabolismo , Oxirredução , Solventes/química , Temperatura Ambiente , alfa-Tocoferol/farmacologia
9.
Biomater Sci ; 7(9): 3898-3905, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31317137

RESUMO

To target a response to a high oxidative stress environment of inflammatory or tumor sites, various reactive oxygen species (ROS) sensitive polymers have been developed as drug delivery systems. In this study, a novel oxidation sensitive copolymer, phenylboronic acid pinacol ester-functionalized methoxyl poly(ethylene glycol)-block-poly(phthalic anhydride-alter-glycidyl propargyl ether) (mPEG-b-P(PA-alt-GPBAe)), was designed and synthesized by ring-opening alternating copolymerization (ROAP) and click reaction. The copolymers could self-assemble into micelles in aqueous solution with an average size of 20.3 ± 9.3 nm, and are able to load hydrophobic anticancer drug (doxorubicin, DOX) with a high encapsulation efficiency of 75.2%. Interestingly, the encapsulated drug showed accelerated release in the trigger of H2O2, or at low pH values. The copolymers have low cytotoxicity indicated by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay towards 4T1 cells, which showed cell viabilities of more than 80% with treatment of our copolymers at concentrations up to 0.5 mg mL-1. The effective uptake of the drug-loaded micelles by 4T1 cells was investigated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) analysis. Finally, compared with free DOX, the DOX-loaded nanoparticles exhibited a better antitumor effect and had lower systemic toxicity in 4T1 tumor-bearing mice. Therefore, this new kind of copolymer acting as a stimuli-responsive nanocarrier should represent a promising therapeutic platform for cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Ácidos Borônicos/química , Doxorrubicina/administração & dosagem , Nanocápsulas/química , Polímeros/química , Animais , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Ésteres/química , Humanos , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Micelas , Oxirredução , Polietilenoglicóis/química
10.
J Agric Food Chem ; 67(31): 8548-8558, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31266305

RESUMO

Herein, we report a double enzyme system to degrade 12 phthalate esters (PAEs), particularly bulky PAEs, such as the widely used bis(2-ethylhexyl) phthalate (DEHP), in a one-pot cascade process. A PAE-degrading bacterium, Gordonia sp. strain 5F, was isolated from soil polluted with plastic waste. From this strain, a novel esterase (GoEst15) and a mono(2-ethylhexyl) phthalate hydrolase (GoEstM1) were identified by homology-based cloning. GoEst15 showed broad substrate specificity, hydrolyzing DEHP and 10 other PAEs to monoalkyl phthalates, which were further degraded by GoEstM1 to phthalic acid. GoEst15 and GoEstM1 were heterologously coexpressed in Escherichia coli BL21 (DE3), which could then completely degrade 12 PAEs (5 mM), within 1 and 24 h for small and bulky substrates, respectively. To our knowledge, GoEst15 is the first DEHP hydrolase with a known protein sequence, which will enable protein engineering to enhance its catalytic performance in the future.


Assuntos
Proteínas de Bactérias/química , Esterases/química , Ésteres/química , Gordonia (Bactéria)/enzimologia , Ácidos Ftálicos/química , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biocatálise , Biodegradação Ambiental , Dietilexilftalato/química , Dietilexilftalato/metabolismo , Esterases/genética , Esterases/metabolismo , Ésteres/metabolismo , Gordonia (Bactéria)/genética , Gordonia (Bactéria)/isolamento & purificação , Gordonia (Bactéria)/metabolismo , Hidrólise , Ácidos Ftálicos/metabolismo , Alinhamento de Sequência , Microbiologia do Solo
11.
J Agric Food Chem ; 67(28): 7793-7809, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31274315

RESUMO

Indoxacarb, a commercialized oxadiazine insecticide, nearly irreversibly blocks open/inactivated, but not resting sodium channels. The structure-activity relationships showed that the substituents at the position of the chiral atom in the oxadiazine ring are very important to the biological activity of oxadiazine insecticide. Here we synthesized a series of tricyclic oxadiazine 4a-methyl ester derivatives. The chiral atom in the oxadiazine ring has been epimerized and substituted with either pyrethric acid or cinnamic acid derivatives. Benzene ring in the tricyclic moiety was substituted with a chlorine, fluorine, or bromine atom, and nitrogen-linked benzene ring was substituted with a trifluoromethyl or trifluoromethoxy group. Toxicity of these compounds against Spodoptera litura F. was evaluated. Diastereoisomers of most toxic compounds J7 and J9 with pyrethric acid moiety were separated by flash column chromatography. The more polar diastereoisomers, J7-L-Rf and J9-L-Rf, and compounds J24 and J26 with cinnamic acid moiety exhibited highest insecticidal activities. We further used Monte Carlo energy minimizations to dock compound J7 and J24 in the NavMs-based homology model of the open cockroach sodium channel. In the low-energy binding modes, the compound interacted with residues in the inner pore and domain interfaces, which previously were proposed to contribute to receptors of pyrethroids and sodium channel blocker insecticides. Our results define compound J7 and J24 as a potentially useful optimized hit for the development of multiple sites sodium channel blocker or modulator.


Assuntos
Inseticidas/química , Inseticidas/toxicidade , Oxazinas/química , Oxazinas/toxicidade , Bloqueadores dos Canais de Sódio/química , Bloqueadores dos Canais de Sódio/toxicidade , Animais , Baratas/efeitos dos fármacos , Baratas/metabolismo , Descoberta de Drogas , Ésteres/química , Ésteres/farmacologia , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Modelos Moleculares , Canais de Sódio/química , Canais de Sódio/metabolismo , Spodoptera/efeitos dos fármacos , Spodoptera/metabolismo , Relação Estrutura-Atividade
12.
Environ Sci Pollut Res Int ; 26(24): 24609-24619, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31236858

RESUMO

Phthalates (PAEs) in drinking water sources such as the Yangtze River in developing countries had aroused widespread concern. Here, the water, suspended particulate matter (SPM), and sediment samples were collected from 15 sites in wet and dry seasons in Zhenjiang, for the determination of six PAEs (DMP, DEP, DIBP, DBP, DEHP, and DOP) using the solid-phase extraction (SPE) or ultrasonic extraction coupled with gas chromatography-mass spectrometry (GC-MS). The total concentrations of six PAEs (Σ6PAEs) spanned a range of 2.65-39.31 µg L-1 in water, 1.97-34.10 µg g-1 in SPM, and 0.93-34.70 µg g-1 in sediment. The partition coefficients (Kd1) of PAEs in water and SPM phase ranged from 0.004 to 3.36 L g-1 in the wet season and from 0.12 to 2.84 L g-1 in the dry season. Kd2 of PAEs in water and sediment phase was 0.001-9.75 L g-1 in the wet season and 0.006-8.05 L g-1 in the dry season. The dominant PAEs were DIBP, DBP, and DEHP in water and SPM, DIBP, DEHP, and DOP in sediment. The concentration of DBP in water exceeded the China Surface Water Standard. The discharge of domestic sewage and industrial wastewater might be the main potential sources of PAEs. The risk quotient (RQ) method used for the risk assessment revealed that DBP (0.01 < RQ < 1) posed a medium risk, while DIBP and DEHP (RQ > 1) posed a high environmental risk in water, DIBP (RQ > 1) also showed a high risk in sediment.


Assuntos
Ésteres/análise , Ácidos Ftálicos , Rios/química , Águas Residuárias/análise , China , Cidades , Ésteres/química , Material Particulado/análise , Medição de Risco , Estações do Ano , Esgotos/análise , Águas Residuárias/química
13.
Food Chem Toxicol ; 130 Suppl 1: 110619, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31233879

RESUMO

Butyl 10-undecenoate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog methyl undec-10-enoate (CAS # 111-81-9) show that butyl 10-undecenoate is not expected to be genotoxic. Data on butyl 10-undecenoate and read-across analog methyl undec-10-enoate (CAS # 111-81-9) show that butyl 10-undecenoate is not a safety concern under the current, declared levels of use for the skin sensitization endpoint. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the TTC for a Cramer Class I material, and the exposure to butyl 10-undecenoate is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; butyl 10-undecenoate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; butyl 10-undecenoate was found not to be PBT as per the IFRA Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., PEC/PNEC), are <1.


Assuntos
Ésteres/química , Ésteres/toxicidade , Ácidos Graxos/química , Ácidos Graxos/toxicidade , Perfumes/química , Perfumes/toxicidade , Animais , Relação Dose-Resposta a Droga , Humanos , Medição de Risco , Testes de Toxicidade
14.
J Agric Food Chem ; 67(25): 7167-7173, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31240926

RESUMO

An improved method for solid-phase extraction (SPE)-liquid chromatography-tandem mass spectrometry was developed to analyze eight monoalkyl phthalate esters (MPEs) in eight different kinds of porcine tissues. The tissue samples were processed using enzymatic deconjugation with ß-glucuronidase, followed by SPE with Oasis MAX cartridges. A pentafluorophenyl column was first used to solve the coeluting issues of MPE isomers. The limits of detection and recoveries were 0.01-0.6 ng/g and 62.5-123.7%, respectively. The intra- and interday precisions were less than 7.1 and 9.4%, respectively. The robust method was successfully applied for the investigation of MPEs in various porcine tissue samples collected from markets in Beijing, China. The occurrence of MPEs with total concentrations of 48.0-108 ng/g was detected, and monoethylhexyl phthalate was the predominant MPE (accounting for 30-57%) in all of the porcine tissue samples. The results will be helpful in assessing the potential risks of diets that include pork.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ésteres/química , Ésteres/isolamento & purificação , Músculos/química , Ácidos Ftálicos/química , Ácidos Ftálicos/isolamento & purificação , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Animais , China , Contaminação de Alimentos/análise , Carne/análise , Suínos
15.
Nat Chem Biol ; 15(7): 721-729, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209347

RESUMO

Production of free fatty acids (FFAs) and derivatives from renewable non-food biomass by microbial fermentation is of great interest. Here, we report the development of engineered Rhodococcus opacus strains producing FFAs, fatty acid ethyl esters (FAEEs) and long-chain hydrocarbons (LCHCs). Culture conditions were optimized to produce 82.9 g l-1 of triacylglycerols from glucose, and an engineered strain with acyl-coenzyme A (CoA) synthetases deleted, overexpressing three lipases with lipase-specific foldase produced 50.2 g l-1 of FFAs. Another engineered strain with acyl-CoA dehydrogenases deleted, overexpressing lipases, foldase, acyl-CoA synthetase and heterologous aldehyde/alcohol dehydrogenase and wax ester synthase produced 21.3 g l-1 of FAEEs. A third engineered strain with acyl-CoA dehydrogenases and alkane-1 monooxygenase deleted, overexpressing lipases, foldase, acyl-CoA synthetase and heterologous acyl-CoA reductase, acyl-ACP reductase and aldehyde deformylating oxygenase produced 5.2 g l-1 of LCHCs. Metabolic engineering strategies and engineered strains developed here may help establish oleaginous biorefinery platforms for the sustainable production of chemicals and fuels.


Assuntos
Ésteres/metabolismo , Ácidos Graxos/biossíntese , Hidrocarbonetos/metabolismo , Engenharia Metabólica , Rhodococcus/metabolismo , Ésteres/química , Ácidos Graxos/química , Hidrocarbonetos/química
16.
Nat Commun ; 10(1): 2661, 2019 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-31209228

RESUMO

The 1,2-dicarbonyl motif is vital to biomolecules, especially natural products and pharmaceuticals. Conventionally, 1,2-dicarbonyl compounds are prepared via an α-keto acyl chloride. Based on the methods used in nature, a transition-metal-free approach for the synthesis of an α-ketothioester reagent via the combination of an α-hydroxyl ketone, elemental sulfur and a benzyl halide is reported. Mechanistic studies demonstrate that the trisulfur radical anion and the α-carbon radical of the α-hydroxy ketone are involved in this transformation. The dicarbonylation of a broad range of amines and amino acids, and importantly, cross couplings with aryl borates to construct dicarbonyl-carbon bonds are realized under mild conditions by employing this stable and convenient α-ketothioester as a 1,2-dicarbonyl reagent. The dicarbonyl-containing drug indibulin and the natural product polyandrocarpamide C, which possess multiple heteroatoms and active hydrogen functional groups, can be efficiently prepared using the designed 1,2-dicarbonyl reagent.


Assuntos
Ésteres/química , Cetonas/química , Compostos de Enxofre/química , Catálise , Indicadores e Reagentes/síntese química , Estrutura Molecular
17.
Chemistry ; 25(44): 10375-10384, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31090112

RESUMO

The ester bond as a universal linker has recently been applied in gene delivery systems owing to its efficient gene release by electrostatic repulsion after its cleavage. However, the ester bond is nonlabile and is difficult to cleave in cells. This work reports a method in which a secondary amine was introduced to the ß-position of the ester bond to generate a hydrogen-bond cyclization (HBC) structure that can make the ester bond hydrolysis ultrafast. A series of molecules comprising ultrasensitive esters that can be activated by H2 O2 were synthesized, and it was found that those able to form an HBC structure showed complete ester hydrolysis within 5 h in both water and phosphate-buffered saline solution, which was several times faster than other methods reported. Then, a series of amphiphilic poly(amidoamine) dendrimers were constructed, comprising the ultrasensitive ester groups for gene delivery; it was found that they could effectively release genes under quite a low concentration of H2 O2 (<200 µm) and transport them into the nucleus within 2 h in Hela cells with high safety. Their gene transfection efficiencies were higher than that of PEI25k . The results demonstrated that the hydrogen-bond-induced ultrasensitive esters could be powerfully applied to construct gene delivery systems.


Assuntos
DNA/química , Dendrímeros/química , Ésteres/química , Técnicas de Transferência de Genes , Poliaminas/química , Linhagem Celular Tumoral , Sobrevivência Celular , Ciclização , DNA/administração & dosagem , Proteínas de Fluorescência Verde/genética , Humanos , Ligações de Hidrogênio , Peróxido de Hidrogênio/química , Hidrólise , Cinética , Transfecção
18.
J Oleo Sci ; 68(6): 573-580, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31092800

RESUMO

Thioester surfactants, [C12H25N(CH3)2(CH2)mSCOCH3] Br (C12mSAc, m = 4, 11, 12), yielded thiol surfactants via thiol-thioester exchange upon addition of dithiothreitol in aqueous solution. The thiolthioester exchange reaction was enhanced in a micellar system owing to the concentration effect. The enhanced aggregation upon deprotection of the thioacetate group was observed by dynamic light scattering measurements. The thiol surfactants yielded disulfide-linked gemini surfactants upon air oxidation and incubation with hydrogen peroxide. In contrast, the thiol surfactants yielded thioester double-tailed products by esterolytic reactions with p-nitrophenyl hexanoate. The introduction of an alkyl chain to the second side chain significantly decreased the critical micelle concentration and induced the micellar growth.


Assuntos
Ésteres/química , Compostos de Sulfidrila/química , Tensoativos/química , Caproatos/química , Ditiotreitol/química , Difusão Dinâmica da Luz , Esterificação , Peróxido de Hidrogênio/química , Nitrobenzenos/química , Oxirredução , Compostos de Amônio Quaternário , Soluções , Água
19.
Phys Chem Chem Phys ; 21(19): 10105-10113, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31062768

RESUMO

Enoyl thioester reductase from Candida tropicalis (Etr1p) catalyzes the NADPH-dependent conversion of enoyl thioesters into acyl thioesters, which are essential in fatty acid and second metabolite biosynthesis. In this paper, we explored the detailed catalytic mechanism of Etr1p by performing QM/MM calculations. Here, we focused on the formation of the covalent ene adduct intermediate and the proton transfer from Tyr79 to the substrate. Our calculation results reveal that the formation of the stable covalent ene adduct follows the Michael addition mechanism rather than the electrocyclic ene reaction. In addition, the ene adduct intermediate can reversibly decompose into the carbanion, and the proton of Tyr79 undertakes a direct electrophilic attack on the substrate to yield the product. In addition, three crystal water molecules do not participate in the catalytic reaction, but they play a crucial role in the hydride transfer and the proton transfer processes by forming a hydrogen bond network. These findings presented here would benefit our understanding of the catalytic mechanism of the NADPH-dependent enzyme.


Assuntos
Candida tropicalis/enzimologia , Ésteres/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Compostos de Enxofre/metabolismo , Biocatálise , Ésteres/química , Simulação de Dinâmica Molecular , Estrutura Molecular , Teoria Quântica , Compostos de Enxofre/química
20.
Chem Commun (Camb) ; 55(49): 7029-7032, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31140482

RESUMO

A traceless thioester-producing protocol featuring carboxypeptidase Y-mediated hydrazinolysis of cysteinyl prolyl leucine-tagged peptides has been developed. The hydrazinolysis followed by thioesterification affords cysteinyl prolyl thioesters. Self-editing of the tag and subsequent trans-thioesterification yields peptide thioesters. The developed protocol was successfully applied to the conversion of recombinant proteins to thioesters.


Assuntos
Carboxipeptidases/metabolismo , Cisteína/metabolismo , Ésteres/metabolismo , Hidrazinas/metabolismo , Compostos de Sulfidrila/metabolismo , Cisteína/química , Ésteres/química , Hidrazinas/química , Conformação Molecular , Compostos de Sulfidrila/química
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