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1.
Chem Commun (Camb) ; 55(86): 12916-12919, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31603445

RESUMO

An enantioselective aerobic decarboxylative Povarov reaction of N-aryl α-amino acids with methylenephthalimidines through cooperative photoredox and chiral Brønsted acid catalysis is reported. With a transition metal-free dual catalytic system including a chiral phosphoric acid and DPZ as a photosensitizer mediated by visible light, the transformations provided a series of valuable chiral isoindolin-1-ones containing a 3,3-spiro-tetrahydroquinoline-based stereocenter in high yields (up to 83%) with good to excellent enantioselectivities (up to 98% ee) and excellent diastereoselectivity (>20 : 1 dr).


Assuntos
Aminoácidos/química , Luz , Ácidos Fosfóricos/química , Ftalimidas/química , Catálise , Oxirredução , Compostos de Espiro/química , Estereoisomerismo
2.
J Chem Phys ; 151(14): 144307, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615216

RESUMO

Historically, structure determination of nanocrystals, proteins, and macromolecules required the growth of high-quality crystals sufficiently large to diffract X-rays efficiently while withstanding radiation damage. The development of the X-ray free-electron laser has opened the path toward high resolution single particle imaging, and the extreme intensity of the X-rays ensures that enough diffraction statistics are collected before the sample is destroyed by radiation damage. Still, recovery of the structure is a challenge, in part due to the partial fragmentation of the sample during the diffraction event. In this study, we use first-principles based methods to study the impact of radiation induced ionization of six amino acids on the reconstruction process. In particular, we study the fragmentation and charge rearrangement to elucidate the time scales involved and the characteristic fragments occurring.


Assuntos
Aminoácidos/química , Aminoácidos/efeitos da radiação , Teoria da Densidade Funcional , Modelos Químicos , Simulação de Dinâmica Molecular , Eletricidade Estática , Fatores de Tempo , Raios X
3.
J Chem Phys ; 151(14): 144504, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615223

RESUMO

In this work, a R1SM approach was applied for the calculation of ideal-gas thermodynamic properties of five amino acids with aliphatic side chains: glycine, alanine, valine, leucine, and isoleucine. The first step of the calculation was an extensive conformational analysis that located several conformers not reported previously. A new systematic and user-friendly nomenclature of the conformers was introduced, and the stable conformers were clearly assigned with the previously used labeling where possible. Stability and calculated relative energies of the conformers were compared between various levels of theory and with several experimental studies, demonstrating a good performance of the selected B3LYP-D3/6-311+G(2df,p) level of theory. As a second step, the theoretically calculated vibrational frequencies were compared to the previously reported experimental spectra to verify the performance of the applied double-linear scaling factor. Finally, ideal-gas heat capacities, enthalpies, and absolute entropies were calculated, accounting for all stable conformers using the R1SM model. The resulting thermodynamic data are presented for the first time, since they cannot be determined experimentally and their rigorous calculation requires a complex thermodynamic model.


Assuntos
Aminoácidos/química , Termodinâmica , Teoria da Densidade Funcional , Gases/química , Modelos Químicos , Conformação Molecular , Estatística como Assunto
4.
Adv Exp Med Biol ; 1148: 173-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482500

RESUMO

Cancer treatment has greatly improved over the last 50 years, but it remains challenging in several cases. Useful therapeutic targets are normally unique peculiarities of cancer cells that distinguish them from normal cells and that can be tackled with appropriate drugs. It is now known that cell metabolism is rewired during tumorigenesis and metastasis as a consequence of oncogene activation and oncosuppressors inactivation, leading to a new cellular homeostasis typically directed towards anabolism. Because of these modifications, cells can become strongly or absolutely dependent on specific substrates, like sugars, lipids or amino acids. Cancer addictions are a relevant target for therapy, as removal of an essential substrate can lead to their selective cell-cycle arrest or even to cell death, leaving normal cells untouched. Enzymes can act as powerful agents in this respect, as demonstrated by asparaginase, which has been included in the treatment of Acute Lymphoblastic Leukemia for half a century. In this review, a short outline of cancer addictions will be provided, focusing on the main cancer amino acid dependencies described so far. Therapeutic enzymes which have been already experimented at the clinical level will be discussed, along with novel potential candidates that we propose as new promising molecules. The intrinsic limitations of their present molecular forms, along with molecular engineering solutions to explore, will also be presented.


Assuntos
Aminoácidos/química , Enzimas/farmacologia , Neoplasias/terapia , Asparaginase , Terapia Enzimática , Humanos , Neoplasias/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras
5.
Chem Commun (Camb) ; 55(79): 11924-11927, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31528965

RESUMO

We report a novel ditopic Gd(iii)-based probe selective to zwitterionic amino acid neurotransmitters (ZNTs) crafted for ratiometric MRI imaging. The probe displayed increased binding affinity to ZNTs and non-synchronized concentration-dependent changes of the r1- and r2-relaxivity. Through the application of a T2/T1 weighted MRI strategy, we demonstrated signal enhancement for cooperatively bound glutamate and γ-aminobutyric acid ZNTs over competitive hydrogencarbonate, which remained MR silent.


Assuntos
Aminoácidos/química , Meios de Contraste/química , Complexos de Coordenação/química , Gadolínio/química , Imagem por Ressonância Magnética/métodos , Neurotransmissores/análise , Bicarbonatos/análise , Técnicas Biossensoriais/métodos , Ácido Glutâmico/análise , Ligantes , Compostos Macrocíclicos/química , Peso Molecular , Ácido gama-Aminobutírico/análise
6.
Chem Commun (Camb) ; 55(71): 10563-10566, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31417990

RESUMO

Besides delivering plausible prebiotic feedstock molecules and high-energy initiators, extraterrestrial impacts could also affect the process of abiogenesis by altering the early Earth's geological environment in which primitive life was conceived. We show that iron-rich smectites formed by reprocessing of basalts due to the residual post-impact heat could catalyze the synthesis and accumulation of important prebiotic building blocks such as nucleobases, amino acids and urea.


Assuntos
Argila/química , Ferro/química , Meteoroides , Silicatos/química , Aminoácidos/química , Catálise , Terra (Planeta) , Evolução Química , Meio Ambiente Extraterreno/química , Origem da Vida , Ureia/química
7.
Chem Commun (Camb) ; 55(72): 10768-10771, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31432821

RESUMO

By covalent combination of a chiral amino acid, lipid, and achiral phenothiazine derivative, a reaction-based chiroptical probe, PTZ-D, was obtained. PTZ-D could self-assemble into a chiral organogel realizing the chirality transformation from a chiral amino acid to a self-assembled system and displaying unprecedented chiroptical monitoring of ClO- with switchable CPL signals.


Assuntos
Aminoácidos/química , Ácido Hipocloroso/análise , Luminescência , Imagem Óptica , Géis/síntese química , Géis/química , Estrutura Molecular , Tamanho da Partícula
8.
Phys Chem Chem Phys ; 21(34): 18501-18515, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31411212

RESUMO

Cohesive properties (lattice and cohesive energy of the crystal and corresponding sublimation enthalpy) of the complete set of twenty enantiopure anhydrous proteinogenic amino acids are investigated using first-principles calculations. In contrast to neutral amino acid molecules in the vapor phase, all amino acids form crystals in their zwitterionic form. Therefore, reliable ab initio calculations of the proton transfer energy are an indispensable step of such calculations. Simplifying procedures, designed to rationalize the computational cost of the quasi-harmonic approximation, which proves too demanding if performed fully at the given quantum level of theory, are presented and tested. For this purpose, atomic multipoles (up to the quadrupoles) for the amoeba force field are parametrized for all amino acid zwitterions. While the calculated lattice energies of the amino acids range from 235-458 kJ mol-1 in absolute value, the proton transfer energies typically amount to 100-220 kJ mol-1, which translates to sublimation enthalpies ranging from 117-202 kJ mol-1, appreciably exceeding the sublimation enthalpy values common for nonionic molecular crystals. Critically assessed experimental data on sublimation enthalpies are used as a benchmark for comparison of the data calculated in this work. Cohesive properties of most amino acids calculated in this work, combining the PBE-D3(BJ)/PAW and CCSD(T)-F12/aug-cc-pVDZ levels of theory used for predictions of the lattice energies and of the proton transfer energies, respectively, exhibit a reasonable agreement with the experiment. At the same time, this work contains the first published data on cohesive properties for several enantiopure amino acids.


Assuntos
Aminoácidos/química , Simulação por Computador , Cristalização , Transição de Fase , Prótons , Teoria Quântica , Termodinâmica
9.
J Agric Food Chem ; 67(36): 10245-10255, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31389238

RESUMO

Ginseng has been widely used as a functional food in the world because of its well-defined health benefits. Previous studies have confirmed that AD-1, a new ginsenoside derived from ginseng, can ameliorate thioacetamide-induced liver injury and fibrosis in mice. Simultaneously, amino acid supplementation is getting more attention as an important adjuvant therapy in the improvement of hepatopathy. The aim of this study was to conjugate AD-1 with several selected amino acids and investigate the cytotoxicity of the obtained conjugates in activated t-HSC/Cl-6 cells and normal human liver cells (LO2). Structure-activity relationships of conjugates and underlying mechanisms of the effect are also explored. The results indicated that conjugate 7c remarkably inhibited cell proliferation in activated t-HSC/Cl-6 cells (IC50 = 3.8 ± 0.4 µM) and appeared to be nontoxic to LO2. Besides, conjugate 7c had a relatively good plasma stability. Further study demonstrated that inducing S-phase arrest and activation of mitochondrial-mediated apoptosis were included in the mechanisms underlying the efficiency of conjugate 7c. These findings provided further insight into designing functional foods (ginsenoside and amino acid) for the application in prevention or improvement of liver fibrosis.


Assuntos
Aminoácidos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ginsenosídeos/farmacologia , Células Estreladas do Fígado/citologia , Aminoácidos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ginsenosídeos/química , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos
10.
Food Chem ; 298: 125086, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31272050

RESUMO

Methylglyoxal (MGO) is a highly reactive ɑ-dicarbonyl compound that may adversely impact food quality and human health by modifying proteins. The kinetics of the reaction of naringenin with MGO was studied at pH 6-8 and 37 °C by UV-Vis spectrophotometry and reaction products were characterized by liquid chromatography-mass spectrometry (LC-MS/MS). The apparent second order rate constant (k2) increased at pH above the lowest pKa value of naringenin, indicating deprotonated naringenin as the main reactant. A Lederer-Manasse type reaction mechanism is suggested, with dehydration of the MGO-dihydrate as a rate determining step. The quantitative data obtained in the present study was used to simulate the competitive reaction between MGO and nucleophilic amino acid residues (Lys, Arg and Cys) and naringenin in milk. It is predicted that naringenin will be able to efficiently trap MGO during storage of milk, although the reversible trapping of MGO by Cys residues is initially kinetically favourable.


Assuntos
Flavanonas/química , Aldeído Pirúvico/química , Aminoácidos/química , Cromatografia Líquida , Concentração de Íons de Hidrogênio , Cinética , Proteínas do Leite/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Espectrometria de Massas em Tandem
11.
J Chem Theory Comput ; 15(8): 4535-4546, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31264415

RESUMO

Anabaena Sensory Rhodopsin (ASR), a microbial photoactive protein featuring the retinal chromophore in two different conformations, exhibits a pH-dependent electronic absorption spectrum. Using the recently developed CpHMD-then-QM/MM multiscale protocol applied to ASR embedded in a membrane model, the pH-induced changes in its maximum absorption wavelength have been reproduced and analyzed. While the acidic tiny red-shift is essentially correlated with the deprotonation of an aspartic acid located on the ASR extracellular side, the larger blue-shift experimentally reported at pH values larger than 5 involves a cluster of titrating residues sitting on the cytoplasmic side. The ASR pH-dependent spectrum is the consequence of the competitive stabilization of retinal ground and excited states by the protein electrostatic potential.


Assuntos
Aminoácidos/química , Anabaena/química , Proteínas de Bactérias/química , Nostoc/química , Rodopsinas Sensoriais/química , Aminoácidos/análise , Ácido Aspártico/análise , Ácido Aspártico/química , Concentração de Íons de Hidrogênio , Modelos Moleculares , Prótons , Espectrofotometria , Eletricidade Estática
12.
J Enzyme Inhib Med Chem ; 34(1): 1178-1185, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31282230

RESUMO

The activation of the ß-class carbonic anhydrases (CAs, EC 4.2.1.1) from the bacteria Brucella suis and Francisella tularensis with amine and amino acids was investigated. BsuCA 1 was sensitive to activation with amino acids and amines, whereas FtuCA was not. The most effective BsuCA 1 activators were L-adrenaline and D-Tyr (KAs of 0.70-0.95 µM). L-His, L-/D-Phe, L-/D-DOPA, L-Trp, L-Tyr, 4-amino-L-Phe, dopamine, 2-pyridyl-methylamine, D-Glu and L-Gln showed activation constants in the range of 0.70-3.21 µM. FtuCA was sensitive to activation with L-Glu (KA of 9.13 µM). Most of the investigated compounds showed a weak activating effect against FtuCA (KAs of 30.5-78.3 µM). Many of the investigated amino acid and amines are present in high concentrations in many tissues in vertebrates, and their role in the pathogenicity of the two bacteria is poorly understood. Our study may bring insights in processes connected with invasion and pathogenic effects of intracellular bacteria.


Assuntos
Aminas/farmacologia , Aminoácidos/farmacologia , Brucella suis/enzimologia , Anidrases Carbônicas/metabolismo , Ativação Enzimática/efeitos dos fármacos , Francisella tularensis/enzimologia , Aminas/química , Aminoácidos/química , Anidrases Carbônicas/genética , Relação Estrutura-Atividade
13.
J Enzyme Inhib Med Chem ; 34(1): 1247-1258, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31286782

RESUMO

A series of N1,N3-bis (1-oxopropan-2-yl) isophthalamide-based derivatives 4-16 were prepared and their structures were confirmed by different spectral tools. The cytotoxic potentiality of novel compounds 4-16 was assessed by the MTT assay method on colon, lung and breast tumour cell lines. Compound 5 gave the most significant specificity anticancer activity with safety response on normal cell lines. In vitro enzyme assay and several apoptotic parameters were examined to elucidate the mode of action of compound 5. Molecular docking studies also were simulated to put insight and give better understanding to its structural features.


Assuntos
Aminoácidos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Relação Estrutura-Atividade
14.
J Agric Food Chem ; 67(31): 8706-8714, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31310118

RESUMO

Gradients in the contents and compositions of gluten proteins and free amino acids and the expression levels of gluten protein genes in developing wheat caryopses were determined by dividing the caryopsis into three longitudinal sections, namely, proximal (En1), middle (En2), and distal (En3) to embryo. The total gluten protein content was lower in En1 than in En2 and En3, with decreasing proportions of HMW-GS, LMW GS, and α/ß- and γ-gliadins and increasing proportions of ω-gliadins. These differences were associated with the abundances of gluten protein transcripts. Gradients in the proportions of the gluten protein polymers which affect dough processing quality also occurred, but not in total free amino acids. Microscopy showed that the lower gluten protein content in En1 may have resulted, at least in part, from the presence of modified cells in the dorsal part of En1, but the reasons for the differences in composition are not known.


Assuntos
Aminoácidos/química , Glutens/química , Triticum/química , Triticum/embriologia , Farinha/análise , Glutens/genética , Glutens/metabolismo , Triticum/genética , Triticum/metabolismo
15.
J Agric Food Chem ; 67(31): 8441-8451, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31339045

RESUMO

The increase in the atmospheric CO2 concentration is predicted to influence wheat production and grain quality and nutritional properties. In the present study, durum wheat (Triticum durum Desf. cv. Sula) was grown under two different CO2 (400 versus 700 µmol mol-1) concentrations to examine effects on the crop yield and grain quality at different phenological stages (from grain filling to maturity). Exposure to elevated CO2 significantly increased aboveground biomass and grain yield components. Growth at elevated CO2 diminished the elemental N content as well as protein and free amino acids, with a typical decrease in glutamine, which is the most represented amino acid in grain proteins. Such a general decrease in nitrogenous compounds was associated with altered kinetics of protein accumulation, N remobilization, and N partitioning. Our results highlight important modifications of grain metabolism that have implications for its nutritional quality.


Assuntos
Dióxido de Carbono/metabolismo , Sementes/crescimento & desenvolvimento , Triticum/metabolismo , Aminoácidos/química , Aminoácidos/metabolismo , Dióxido de Carbono/análise , Cinética , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Sementes/química , Sementes/metabolismo , Triticum/química , Triticum/crescimento & desenvolvimento
16.
Adv Exp Med Biol ; 1140: 531-539, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347069

RESUMO

Stable isotope labeling by amino acids in cell culture (SILAC) is a powerful approach for high-throughput quantitative proteomics. SILAC allows highly accurate protein quantitation through metabolic encoding of whole cell proteomes using stable isotope labeled amino acids. Since its introduction in 2002, SILAC has become increasingly popular. In this chapter we review the methodology and application of SILAC, with an emphasis on three research areas: dynamics of posttranslational modifications, protein-protein interactions, and protein turnover.


Assuntos
Aminoácidos/química , Técnicas de Cultura de Células , Marcação por Isótopo , Proteômica/métodos , Proteoma
17.
Adv Exp Med Biol ; 1140: 575-583, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347072

RESUMO

The global measurement of assembly and turnover of protein containing complexes within cells has advanced with the development of pulse stable isotope labelled amino acid approaches. Stable isotope labeling with amino acids in cell culture (SILAC) allows the incorporation of "light" 12-carbon amino acids or "heavy" 13-carbon amino acids into cells or organisms and the quantitation of proteins and peptides containing these amino acid tags using mass spectrometry. The use of these labels in pulse or pulse-chase scenarios has enabled measurements of macromolecular dynamics in cells, on time scales of several hours. Here we review advances with this approach and alternative or parallel strategies. We also examine the statistical considerations impacting datasets detailing mitochondrial assembly, to highlight key parameters in establishing significance and reproducibility.


Assuntos
Aminoácidos/química , Técnicas de Cultura de Células , Marcação por Isótopo , Espectrometria de Massas , Proteínas/análise , Reprodutibilidade dos Testes
18.
Eur J Med Chem ; 179: 567-575, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279291

RESUMO

In order to find new potential pesticide molecules with antifungal activities, we have designed and synthesized a series of amino acid-oriented poly-substituted tetramic acid derivatives, and evaluated their potential antifungal activities against six kinds of plant pathogenic fungus commonly found in agriculture systematically, including Phomopsis adianticola, Fusarium graminearum, Alternaria tenuis Nees, Magnaporthe oryzae, Gloeosporium theae-sinensis, Sclerotinia sclerotiorum. According to the preliminary bioassay studies, all tested molecules, especially compounds I-2, I-5, I-12, I-15, exhibited significant and broad-spectrum anti-fungal effect in vitro compared to the intermediates M-1, M-2, M-3 and hymexazol. What's more, the inhibition rate of compounds I-5, I-6, I-15 against Phomopsis adianticola reached 74.42%, 60.33%, 65.21%, as well as compounds I-3, I-5, I-15 against Sclerotinia sclerotiorum were 65.65%, 74.92%, 61.36%. Further investigation results indicated that compounds I-2, I-5, I-15 presented obviously inhibitory activities against Phomopsis adianticola compared with hymexazol, which might be considered as the basic active framework for further potential fungicides discovery.


Assuntos
Aminoácidos/farmacologia , Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Pirrolidinonas/farmacologia , Aminoácidos/química , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Compostos Heterocíclicos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirrolidinonas/síntese química , Pirrolidinonas/química , Relação Estrutura-Atividade
19.
Chem Pharm Bull (Tokyo) ; 67(10): 1046-1049, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31341115

RESUMO

A new catalytic system comprising chiral Ag complex and Li aryloxide/bisphosphine oxide is developed for the synthesis of ß2,2-amino acids via direct asymmetric Mannich-type reaction of 4-subsituted isoxazolidin-5-ones. The Mannich adduct is a direct precursor of ß-peptidic compounds otherwise difficult to obtain.


Assuntos
Aminoácidos/síntese química , Carbonatos/química , Complexos de Coordenação/química , Bases de Lewis/química , Lítio/química , Aminoácidos/química , Catálise , Complexos de Coordenação/síntese química , Isoxazóis/química , Estrutura Molecular , Prata/química
20.
J Agric Food Chem ; 67(25): 7190-7196, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31194545

RESUMO

Creatine transporter deficiency (CTD) is caused by a defect in the X-linked creatine transporter SLC6A8 gene leading to severe neurologic and physiologic conditions. Cyclocreatine and phosphocyclocreatine supplementation is seen as a potential treatment, but the presence of these compounds within commercially available dietary supplements presents the risk of self-medication. High-performance liquid chromatography-mass spectrometry (HPLC-MS) is an excellent technique to assess composition of complex amino acid mixtures. Herein, we have developed a facile HPLC-MS method using a cyano column in hydrophilic interaction liquid chromatography (HILIC) mode with isocratic elution over 4 min to identify the main components of two commercially available dietary supplements. The relative standard deviation (RSD) for retention time and extracted ion integrated area are <0.3% and 4%, respectively, showing excellent reproducibility. Cyclocreatine and phosphocyclocreatine were not detectable within the dietary supplements, even at ppm levels, demonstrating the power and importance of the developed HPLC-MS method in analyzing complex mixtures.


Assuntos
Aminoácidos/química , Cromatografia Líquida de Alta Pressão/métodos , Creatinina/análogos & derivados , Imidazolidinas/química , Espectrometria de Massas/métodos , Fosfocreatina/análogos & derivados , Creatinina/química , Suplementos Nutricionais/análise , Fosfocreatina/química
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