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1.
Int J Mol Sci ; 22(3)2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33573283

RESUMO

The synthesis of α-fluorinated methyl ketones has always been challenging. New methods based on the homologation chemistry via nucleophilic halocarbenoid transfer, carried out recently in our labs, allowed us to design and synthesize a target-directed dipeptidyl α,α-difluoromethyl ketone (DFMK) 8 as a potential antiviral agent with activity against human coronaviruses. The ability of the newly synthesized compound to inhibit viral replication was evaluated by a viral cytopathic effect (CPE)-based assay performed on MCR5 cells infected with one of the four human coronaviruses associated with respiratory distress, i.e., hCoV-229E, showing antiproliferative activity in the micromolar range (EC50 = 12.9 ± 1.22 µM), with a very low cytotoxicity profile (CC50 = 170 ± 3.79 µM, 307 ± 11.63 µM, and 174 ± 7.6 µM for A549, human embryonic lung fibroblasts (HELFs), and MRC5 cells, respectively). Docking and molecular dynamics simulations studies indicated that 8 efficaciously binds to the intended target hCoV-229E main protease (Mpro). Moreover, due to the high similarity between hCoV-229E Mpro and SARS-CoV-2 Mpro, we also performed the in silico analysis towards the second target, which showed results comparable to those obtained for hCoV-229E Mpro and promising in terms of energy of binding and docking pose.


Assuntos
Antivirais/química , Coronavirus Humano 229E/metabolismo , Dipeptídeos/química , Cetonas/química , Células A549 , Antivirais/farmacologia , Sítios de Ligação , /virologia , Linhagem Celular , /metabolismo , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , /metabolismo , Termodinâmica , Proteínas da Matriz Viral/química , Proteínas da Matriz Viral/metabolismo , Replicação Viral/efeitos dos fármacos
2.
Phys Chem Chem Phys ; 23(1): 356-367, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33346272

RESUMO

The protein ß2-microglobulin (ß2-m) can aggregate in insoluble amyloid fibrils, which deposit in the skeletal muscle system of patients undergoing long-term haemodialysis. The molecular mechanisms of such amyloidogenesis are still not fully understood. A potential, although debated, triggering factor is the cis to trans isomerization of a specific proline (Pro32) in ß2-m. Here we investigate this process in the native protein and in the aggregation-prone mutant D76N by means of molecular dynamics and the enhanced sampling method metadynamics. Our simulations, including the estimation of the free energy difference between the cis and trans isomers, are in good agreement with in vitro experiments and highlight the importance of the hydrogen bond and hydrophobic interaction network around the critical Pro32 in stabilizing and de-stabilizing the two isomers.


Assuntos
Proteínas Amiloidogênicas/química , Prolina/química , Microglobulina beta-2/química , Proteínas Amiloidogênicas/genética , Dipeptídeos/química , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Mutação Puntual , Conformação Proteica , Estereoisomerismo , Microglobulina beta-2/genética
3.
Food Chem ; 338: 127867, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32829293

RESUMO

This is the first time that active double-layered furcellaran/gelatin hydrolysate films containing Ala-Tyr peptide were developed and characterised for their properties. Afterwards, films were used on Atlantic mackerel stored at -18 °C for 4 months and samples were analysed for changes in their microbiological quality, TVB-N, biogenic amine content, fatty acid composition and TBARS. Active films had higher TS (13.4 MPa) and lower WS (62.8%). The films showed no DPPH radical scavenging properties but high FRAP (6.6 mMol Trolox/mg). No significant effects on the oxidation of fish samples were observed with TBARS increasing from 12.04 to 22.50 mg/kg. Freezing successfully inhibited the growth of microorganisms and no differences in microbiological growth or biogenic amine formation were observed. However, the application of films inhibited the formation of TVB-N. Antimicrobiological properties of the film should be further investigated during storage of perishable food products at temperatures above 0 °C.


Assuntos
Alginatos/química , Dipeptídeos/química , Armazenamento de Alimentos/métodos , Gelatina/química , Perciformes/metabolismo , Gomas Vegetais/química , Animais , Antioxidantes/química , Aminas Biogênicas/análise , Cromatografia Líquida de Alta Pressão , Temperatura Baixa , Dipeptídeos/farmacologia , Conservação de Alimentos/métodos , Peptídeos/química , Peptídeos/farmacologia , Perciformes/microbiologia , Pseudomonas/efeitos dos fármacos , Pseudomonas/isolamento & purificação , Resistência à Tração
4.
Food Chem ; 338: 128018, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32932086

RESUMO

The umami-enhancing effect of typical kokumi-active γ-glutamyl peptides was verified by sensory evaluation. To investigate the umami-enhancing molecular mechanism of the peptide on monosodium glutamate (MSG) taste, a novel hypothetical receptor, taste type 1 receptor 3 (T1R3)-MSG complex, was constructed. These peptides demonstrated strong interactions with T1R3-MSG. Moreover, four amino acid residues, Glu-301, Ala-302, Thr-305, and Ser-306, were critical in ligand-receptor interactions. In detail, γ-Glu-γ-Glu-Val (γ-E-γ-EV) readily interacts with T1R3 through hydrogen bonds and hydrophobic interactions. While γ-E-γ-EV did not bind to MSG, γ-Glu-Val (γ-EV) and γ-Glu-Leu (γ-EL) showed high binding affinity to MSG and interacted with T1R3 through hydrophobic bonds suggesting that the interactions between dipeptides and T1R3-MSG were weaker than tripeptides. These results demonstrated that kokumi-active γ-glutamyl peptides could enhance the umami taste of MSG, and exhibit synergistic effects in activating T1R3. This study provides a theoretical reference for interactions between the novel umami-enhancing substances and umami receptor.


Assuntos
Dipeptídeos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Glutamato de Sódio/metabolismo , Paladar , Adulto , Aminoácidos/química , Aminoácidos/metabolismo , Dipeptídeos/química , Feminino , Aromatizantes/química , Aromatizantes/farmacologia , Humanos , Ligação de Hidrogênio , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Simulação de Acoplamento Molecular , Receptores Acoplados a Proteínas-G/química , Glutamato de Sódio/química , Glutamato de Sódio/farmacologia , Paladar/efeitos dos fármacos
5.
Nat Commun ; 11(1): 5115, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037228

RESUMO

Recurrent neural networks have led to breakthroughs in natural language processing and speech recognition. Here we show that recurrent networks, specifically long short-term memory networks can also capture the temporal evolution of chemical/biophysical trajectories. Our character-level language model learns a probabilistic model of 1-dimensional stochastic trajectories generated from higher-dimensional dynamics. The model captures Boltzmann statistics and also reproduces kinetics across a spectrum of timescales. We demonstrate how training the long short-term memory network is equivalent to learning a path entropy, and that its embedding layer, instead of representing contextual meaning of characters, here exhibits a nontrivial connectivity between different metastable states in the underlying physical system. We demonstrate our model's reliability through different benchmark systems and a force spectroscopy trajectory for multi-state riboswitch. We anticipate that our work represents a stepping stone in the understanding and use of recurrent neural networks for understanding the dynamics of complex stochastic molecular systems.


Assuntos
Idioma , Memória , Modelos Estatísticos , Redes Neurais de Computação , Inteligência Artificial , Dipeptídeos/química , Cinética , Cadeias de Markov , Simulação de Dinâmica Molecular , Imagem Individual de Molécula
6.
J Chromatogr A ; 1632: 461585, 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33039941

RESUMO

The separation of the ll- and dd-enantiomers of the dipeptides Ala-Phe, Ala-phenylglycine (Phg), Ala-homoPhe, Ala-ß-Phe, Gly-Phe and ß-Ala-Phe was studied by capillary electrophoresis in the presence of negatively charged α-, ß- and γ-cyclodextrin (CD) derivatives. Analysis was performed under standardized conditions in fused-silica capillaries at pH 2.5, 3.5 and 5.3. All analyte enantiomers could be separated at pH 2.5 under at least one of the experimental conditions. Especially ß-CD derivatives proved to be effective chiral selectors. The enantiomer migration order depended on CD cavity size and substituent type, while peptide structure had only a minor effect. Upon increasing the pH from 2.5 to 5.3, reversal of the enantiomer migration order was observed frequently. Investigation of the apparent and, in the case of randomly substituted CDs, averaged complexation constants and mobilities of the diastereomeric peptide enantiomer-CD complexes indicated that in most cases the migration order in the presence of sulfated α-, ß- and γ-CD and heptakis(6-O-sulfo)-ß-CD could be explained by the stronger binding of the second migrating analyte by the CD at pH 2.5. However, in few cases the weaker bound enantiomer migrated second, which could be attributed to the higher mobility of the respective CD complexes. At pH 5.3, similar data were obtained for sulfated ß-CD and heptakis(6-O-sulfo)-ß-CD, i.e. the strength of the complexes determined the migration order for some peptides, while the migration sequence was based on the apparent (and averaged) mobility of the diastereomeric analyte-CD complexes in other cases.


Assuntos
Ciclodextrinas/química , Dipeptídeos/isolamento & purificação , Eletroforese Capilar/métodos , Dipeptídeos/química , Eletrólitos/química , Concentração de Íons de Hidrogênio , Cinética , Peptídeos/química , Estereoisomerismo
7.
J Oleo Sci ; 69(11): 1427-1436, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33055444

RESUMO

This paper presents the results of a kinetic study performed between ninhydrin and a Ni(II) dipeptide complex under various conditions. The rate of formation of the imine adduct was measured spectrophotometrically both in plain aqueous media and in aqueous micellar media in which CTAB (cetyltrimethylammonium bromide) is used as the surfactant. These studies were carried out at pH 5 and over a temperature a range of 50 to 70°C. Studies were also conducted to elucidate the effect of some organic sodium salts on the rate of this reaction. In these studies, it was found that the formation of imine adduct followed a first-order kinetics with respect to [Ni(II)-Gly-Leu]+ in both aqueous and micellar medium. A fractional-order kinetics was observed with respect to ninhydrin, again in both aqueous and micellar media. Increase in the total concentration of CTAB from 0 to 40×10-3 mol dm-3 resulted in approximately two folds increase in the pseudo-first-order rate constant (kψ). The rate constant (kΨ) in micellar medium first increased with increase in CTAB concentration, reached a maximum value, and finally, with further increase in CTAB concentration, a decreasing effect was observed. Quantitative kinetic analysis of kψ-[CTAB] data was performed on the basis of the pseudo-phase model of the micelles. The rate profile in presence of CTAB suggests a cooperative effect in the enhanced formation of the imine adduct as is commonly found in enzyme catalyzed reactions. Addition of organic sodium salts (such as benzoate, salicylate and tosylate) enhanced the rate at lower concentrations but rates start to decrease at higher concentrations. This suggests that tightly binding organic counter-anions were the most effective. Viscosity of the reaction media seems to affect the kinetic behavior in micellar media.


Assuntos
Cetrimônio/química , Dipeptídeos/química , Iminas/química , Metais/química , Ninidrina/química , Tensoativos/química , Ânions/química , Benzoatos/química , Catálise , Concentração de Íons de Hidrogênio , Micelas , Fenômenos de Química Orgânica , Salicilatos/química , Espectrofotometria , Temperatura , Viscosidade , Água/química
8.
Nat Commun ; 11(1): 3818, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732937

RESUMO

The formation of peptide bonds by energetic processing of amino acids is an important step towards the formation of biologically relevant molecules. As amino acids are present in space, scenarios have been developed to identify the roots of life on Earth, either by processes occurring in outer space or on Earth itself. We study the formation of peptide bonds in single collisions of low-energy He2+ ions (α-particles) with loosely bound clusters of ß-alanine molecules at impact energies typical for solar wind. Experimental fragmentation mass spectra produced by collisions are compared with results of molecular dynamics simulations and an exhaustive exploration of potential energy surfaces. We show that peptide bonds are efficiently formed by water molecule emission, leading to the formation of up to tetrapeptide. The present results show that a plausible route to polypeptides formation in space is the collision of energetic ions with small clusters of amino acids.


Assuntos
Aminoácidos/química , Simulação de Dinâmica Molecular , Peptídeos/química , Termodinâmica , beta-Alanina/química , Dipeptídeos/síntese química , Dipeptídeos/química , Íons/química , Oligopeptídeos/síntese química , Oligopeptídeos/química , Peptídeos/síntese química , Espectrometria de Massas por Ionização por Electrospray/métodos , Água/química
9.
J Chromatogr A ; 1626: 461371, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32797850

RESUMO

Effect of mobile phase (water-methanol) composition on the enantioseparation of dipeptides on the chiral stationary phase Chirobiotic R was investigated using Ala-Ala, Leu-Leu, Gly-Leu, and Leu-Gly as case studies. The lipophilicity of dipeptides was found to be an essential factor in the dependence of their retention on the methanol percentage, the retention factor of lipophobic dipeptides increasing monotonously and that of lipophilic dipeptides changing according to an asymmetric U-shaped trajectory as methanol concentration increases. The behavior of enantioselectivity as a function of the methanol content also depends on the lipophilicity of dipeptide. For lipophilic Leu-Leu, the dependence has a dome-like shape, and for more lipophobic dipeptides, Ala-Ala and Gly-Leu, it is an increasing function of the methanol concentration. The importance of solvation equilibria in the bulk liquid and on the surface of the stationary phase for the total retention is discussed from the thermodynamic point of view. Special consideration is given to the adsorption of the water-methanol mixture on the surface of the Chirobiotic R stationary phase.


Assuntos
Antibacterianos/química , Cromatografia Líquida de Alta Pressão/métodos , Dipeptídeos/química , Metanol/química , Adsorção , Interações Hidrofóbicas e Hidrofílicas , Estereoisomerismo , Termodinâmica
10.
Biochim Biophys Acta Proteins Proteom ; 1868(9): 140467, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32512181

RESUMO

The degradation of the immunomodulatory octapeptide, thymic humoral factor γ2 (THF-γ2, thymoctonan) has been studied in whole blood samples from human, rat and mouse. The peptide, Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu, was shown to be rapidly degraded by peptidases. The half-life of the intact peptide was less than 6 min at 37 °C in blood from the three species tested. The main fragments formed from THF-γ2 were found to be Glu-Asp-Gly-Pro-Lys-Phe-Leu (2-8), Asp-Gly-Pro-Lys-Phe-Leu (3-8) and Glu-Asp-Gly-Pro-Lys (2-6) in human and in rat blood and 2-8 and 2-6 in mouse blood. Analysis of the time course of degradation revealed a sequential removal of single amino acids from the N-terminus (aminopeptidase activities) in a process that was apparently unable to cleave the Gly-Pro bond (positions 4-5 in the peptide) together with an independent cleavage of the Lys-Phe bond (positions 6-7 in the peptide) to release the dipeptide Phe-Leu. This behaviour and the effects of inhibitors showed the involvement of metallo-exopeptidases in the N-terminal digestion and a phosphoramidon-sensitive metallo-endopeptidase in the cleavage of the Lys-Phe bond. The degradation patterns in human blood were modelled in terms of the competing pathways involved approximating to first-order kinetics, and an analytical solution obtained via the method of Laplace Transforms. The half-life of THF degradation in whole rat blood sample was found to be significantly lower than in human or mouse.


Assuntos
Oligopeptídeos/sangue , Oligopeptídeos/metabolismo , Aminopeptidases , Animais , Dipeptídeos/química , Meia-Vida , Humanos , Cinética , Masculino , Camundongos , Modelos Animais , Modelos Teóricos , Neprilisina/metabolismo , Oligopeptídeos/química , Peptídeo Hidrolases , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Wistar
11.
J Chromatogr A ; 1623: 461158, 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32505274

RESUMO

In the present study, the enantioseparation of the ll- and dd-enantiomers of the dipeptides Ala-Phe, Ala-phenylglycine (Phg), Ala-homoPhe, Ala-ß-Phe, Gly-Phe and ß-Ala-Phe was studied by capillary electrophoresis in the presence of native α-, ß- and γ-cyclodextrin (CD) as well as their methyl and hydroxypropyl derivatives. Separations were performed under standardized conditions in fused-silica capillaries at pH 2.5, 3.5 and 9.5. All analyte enantiomers could be separated at acidic pH under at least one of the experimental conditions. ß-CDs proved to be more universal chiral selectors than α- and γ-CDs. Only few alkaline conditions led to an enantioseparation. For a given dipeptide, the enantiomer migration order depended on the type of CD with regard to cavity size and degree of substitution. Little effect was found with regard to the structure of the dipeptides. pH-dependent reversal of the enantiomer migration order upon increasing the pH from 2.5 to 3.5 was observed for all dipeptides with at least one of the ß-CD derivatives. In the case of ß-CD, analysis of the complexation constants and the apparent limiting mobilities of the diastereomeric peptide enantiomer-CD complexes revealed, that the enantiomer migration order of Ala-Phe, Ala-homoPhe and Ala-ß-Phe was determined by the stereoselective complexation by ß-CD at pH 2.5. At pH 3.5 opposite chiral recognition of the enantiomers by ß-CD was found for Ala-Phe and Ala-ß-Phe resulting in the reversed migration order. In contrast, chiral recognition did not change in the case of Ala-homoPhe, but reversal of the enantiomer migration order was based on the apparent mobility of the diastereomeric analyte-CD complexes.


Assuntos
Ciclodextrinas/química , Dipeptídeos/química , Eletroforese Capilar/métodos , Dipeptídeos/isolamento & purificação , Concentração de Íons de Hidrogênio , Estereoisomerismo
12.
Phys Chem Chem Phys ; 22(25): 13867-13871, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32368774

RESUMO

Herein, we present the first rotational study of the AlaAla dipeptide, brought into the gas phase by laser ablation. Two different structures have been unveiled in the isolated environment of a supersonic expansion by Fourier transform microwave spectroscopy. These structures have been identified through their rotational and 14N quadrupole coupling constants. The flexibility of the -NH2 and -COOH ends allows the formation of strong intramolecular interactions giving rise to five- and seven-membered ring configurations.


Assuntos
Alanina/química , Dipeptídeos/química , Análise de Fourier , Micro-Ondas , Conformação Proteica , Rotação
13.
J Phys Chem Lett ; 11(10): 4147-4155, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32368918

RESUMO

Helical structures are important features of many important biomacromolecules such as double helices and single α-helices in DNA and protein, respectively, yet the self-organization of short oligopeptides (<3) or independent amino acids into artificial helical structures on the atomic level remains mysterious. Here we present the direct construction of artificial double and single helices from N-terminated aryl amino acids (ferrocene phenylalanine (Phe) conjugates) despite both Phe and Phe-Phe dipeptide self-aggregations adopting supramolecular ß-sheet structures, which also demonstrated chirality evolution exposed to small molecular binders. In the solid state, the box-shaped building unit stacks into a double helix with enantiomer-resolved handedness driven orthogonally by H-bonds and the CH-π interaction. The entire double helix is noncovalently linked except for the hybridization regions. Asymmetric H-bonds between carboxylic acids and amides facilitates the one-dimensional helical packing of amino acid residues. The ditopic building unit adopts intramolecular H-bonds, facilitating single-strand helix formation. In aqueous self-assemblies, the superhelical structures were retained, which underwent chirality transfer and handedness inversion upon complexation orthogonally by H-bonds and charge-transfer interaction, showing adaptivity to environmental factors.


Assuntos
Aminoácidos/síntese química , Dipeptídeos/química , Aminoácidos/química , Ligação de Hidrogênio , Modelos Moleculares , Estrutura Secundária de Proteína
14.
Chemistry ; 26(38): 8372-8376, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32428282

RESUMO

Transient self-assembly of dipeptide nanofibers with lifetimes that are predictably variable through dipeptide sequence design are presented. This was achieved using 1,8-naphthalimide (NI) amino acid methyl-esters (Phe, Tyr, Leu) that are biocatalytically coupled to amino acid-amides (Phe, Tyr, Leu, Val, Ala, Ser) to form self-assembling NI-dipeptides. However, competing hydrolysis of the dipeptides results in disassembly. It was demonstrated that the kinetic parameters like lifetimes of these nanofibers can be predictably regulated by the thermodynamic parameter, namely the self-assembly propensity of the constituent dipeptide sequence. These lifetimes could vary from minutes, to hours, to permanent gels that do not degrade. Moreover, the in-built NI fluorophore was utilized to image the transient nanostructures in solution with stimulated emission depletion (STED) based super-resolution fluorescence microscopy.


Assuntos
Dipeptídeos/química , Nanofibras/química , Nanoestruturas/química , Naftalimidas/química , Aminoácidos , Géis , Hidrólise , Cinética
15.
Sci Rep ; 10(1): 7070, 2020 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341441

RESUMO

The Chilean hazelnut (Gevuina avellana Mol., Proteaceae) is a southern South American nut consumed as a snack and included in different preparations of traditional Chilean cuisine. Recently we described the fatty acid profile, oxylipins, phenolic compounds, as well as the antioxidant capacity. The main compounds of the phenolic-enriched extract were only tentatively identified by spectrometric means. In the present work, we describe the isolation and full characterization of a cyclic dipeptide cyclo(Arg-Trp) and other compounds from the phenolic enriched extracts of the G. avellana cotyledons. Compounds were isolated by means of counter-current chromatography and structures were established by spectroscopic and spectrometric methods. This is the first report on small peptides in G. avellana and adds evidence on the possible beneficial effects of this nut in human health.


Assuntos
Cotilédone/química , Dipeptídeos , Peptídeos Cíclicos , Proteaceae/química , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação
16.
Chemistry ; 26(43): 9466-9470, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32259330

RESUMO

Macrocycle, cyclo[4] [(1,3-(4,6)-dimethylbezene)[4](2,6-(3,5)-dimethylpyridine (B4P4), shows highly selective binding affinity with protirelin (Pyr-His-Pro-NH2 ; TRH) among the tested 26 drug or drug adductive substrates. The stable complexation in a 1:1 manner was fully characterized in solution, gas phase, and solid state study. Furthermore, B4P4 acts as an efficient TRH inhibitor even at [macrocycle]:[drug] <1:300, both in membrane transport and cellar incubation. The current work provides an unprecedented strategy for macrocycles to be efficiently used in drug target therapy.


Assuntos
Dipeptídeos/química , Piridinas/química , Hormônio Liberador de Tireotropina/farmacologia , Dipeptídeos/metabolismo , Hormônio Liberador de Tireotropina/química , Hormônio Liberador de Tireotropina/metabolismo
17.
Food Chem ; 319: 126540, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32151899

RESUMO

SeMet-Pro-Ser (Se-MPS) is an antioxidant selenopeptide derived from selenized brown rice protein hydrolysates. In this study, the stability of glutathione (GSH), Met-Pro-Ser (MPS), and Se-MPS under different processing conditions, namely, temperature, pH, NaCl, citric acid, light, and gastrointestinal proteases, were evaluated by measuring ABTS+ scavenging and Cr(VI) reduction capacities. The ABTS+ scavenging capacity of GSH under thermal treatment, high salt density, and long-term storage was significantly decreased, while its Cr(VI) reduction activity was relatively stable. No significant change of Se-MPS antioxidant activity was observed under different conditions, except under citric acid. Meanwhile, its Cr(VI) reduction activity was partially or mostly retained under different treatment conditions. However, it displayed negligible ABTS+ scavenging capacity. Se-MPS was superior to GSH and MPS in terms of stability and antioxidant activity and could be a candidate for development of nutraceuticals or functional food.


Assuntos
Antioxidantes/química , Dipeptídeos/química , Oryza/enzimologia , Peptídeos/química , Hidrolisados de Proteína/metabolismo , Antioxidantes/metabolismo , Dipeptídeos/metabolismo , Glutationa/química , Oryza/química , Peptídeos/metabolismo
18.
Chem Pharm Bull (Tokyo) ; 68(3): 234-243, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115530

RESUMO

Diphenhydramine, a sedating antihistamine, is an agonist of human bitter taste receptor 14 (hTAS2R14). Diphenhydramine hydrochloride (DPH) was used as a model bitter medicine to evaluate whether the umami dipeptides (Glu-Glu and Asp-Asp) and their constituent amino acids (Glu, Asp) could suppress its bitterness intensity, as measured by human gustatory sensation testing and using the artificial taste sensor. Various concentrated (0.001-5.0 mM) Glu-Glu, Asp-Asp, Glu and Asp significantly suppressed the taste sensor output of 0.5 mM DPH solution in a dose-dependent manner. The effect of umami dipeptides and their constituent amino acids was tending to be ranked as follows, Asp-Asp > Glu-Glu >> Gly-Gly, and Asp > Glu >> Gly (control) respectively. Whereas human bitterness intensity of 0.5 mM DPH solution with various concentrated (0.5, 1.0, 1.5 mM) Glu-Glu, Asp-Asp, Glu and Asp all significantly reduced bitterness intensity of 0.5 mM DPH solution even though no statistical difference was observed among four substances. The taste sensor outputs and the human gustatory sensation test results showed a significant correlation. A surface plasmon resonance study using hTAS2R14 protein and these substances suggested that the affinity of Glu-Glu, Asp-Asp, Glu and Asp for hTAS2R14 protein was greater than that of Gly-Gly or Gly. The results of docking-simulation studies involving DPH, Glu-Glu and Asp-Asp with hTAS2R14, suggested that DPH is able to bind to a space near the binding position of Glu-Glu and Asp-Asp. In conclusion, the umami dipeptides Glu-Glu and Asp-Asp, and their constituent amino acids, can all efficiently suppress the bitterness of DPH.


Assuntos
Aminoácidos/farmacologia , Dipeptídeos/farmacologia , Difenidramina/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Paladar/efeitos dos fármacos , Aminoácidos/química , Dipeptídeos/química , Difenidramina/química , Relação Dose-Resposta a Droga , Humanos , Ligantes , Modelos Moleculares , Relação Estrutura-Atividade
19.
Sci Rep ; 10(1): 4303, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152427

RESUMO

Single substances within complex vertebrate chemical signals could be physiologically or behaviourally active. However, the vast diversity in chemical structure, physical properties and molecular size of semiochemicals makes identifying pheromonally active compounds no easy task. Here, we identified two volatile cyclic dipeptides, cyclo(L-Leu-L-Pro) and cyclo(L-Pro-L-Pro), from the complex mixture of a chemical signal in terrestrial vertebrates (lizard genus Sceloporus), synthesised one of them and investigated their biological activity in male intra-specific communication. In a series of behavioural trials, lizards performed more chemosensory behaviour (tongue flicks, lip smacks and substrate lickings) when presented with the synthesised cyclo(L-Pro-L-Pro) chemical blend, compared to the controls, the cyclo(L-Leu-L-Pro) blend, or a combined blend with both cyclic dipeptides. The results suggest a potential semiochemical role of cyclo(L-Pro-L-Pro) and a modulating effect of cyclo(L-Leu-L-Pro) that may depend on the relative concentration of both compounds in the chemical signal. In addition, our results stress how minor compounds in complex mixtures can produce a meaningful behavioural response, how small differences in structural design are crucial for biological activity, and highlight the need for more studies to determine the complete functional landscape of biologically relevant compounds.


Assuntos
Comportamento Animal/efeitos dos fármacos , Quimiotaxia , Dipeptídeos/farmacologia , Glândulas Exócrinas/metabolismo , Peptídeos Cíclicos/farmacologia , Compostos Orgânicos Voláteis/farmacologia , Animais , Dipeptídeos/química , Glândulas Exócrinas/efeitos dos fármacos , Lagartos , Peptídeos Cíclicos/química , Compostos Orgânicos Voláteis/química
20.
Chemistry ; 26(39): 8541-8545, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32160344

RESUMO

A straightforward multicomponent Knoevenagel-aza-Michael-cyclocondensation reaction involving readily available hydroxamic acid-derived from naturally occurring α-amino acids allows a diversity-oriented synthesis of novel isoxazolidin-5-ones possessing an N-protected α-amino acid pendant with good to high diastereoselectivities thanks to a match effect with a chiral organocatalyst. These diversely substituted heterocycles, easily isolated as a single diastereoisomer, proved to be versatile platforms for the formation of an array of α/ß-dipeptide fragments.


Assuntos
Aminoácidos/química , Dipeptídeos/síntese química , Dipeptídeos/química , Estrutura Molecular , Estereoisomerismo
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