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1.
Methods Mol Biol ; 1985: 279-302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069740

RESUMO

Although the first application of chiral ligand-exchange chromatography (CLEC) in HPLC dates back to late 1960s, this enantioselective strategy still represents the elective choice for the direct analysis of compounds endowed with chelating moieties. As a specific feature of the CLEC mechanism, the interaction between the chiral selector and the enantiomer does not take place in direct contact. Indeed, it is mediated by a central metal ion that, acting as a Lewis acid, simultaneously coordinates the two species, selector and analyte, through the activation of dative bonds. As a consequence, two diastereomeric mixed ternary complexes are generated in the column, ultimately leading to the stereoisomeric discrimination. CLEC applications can be carried out both with the chiral selector included in the mobile phase (chiral mobile phase, CMP), or as a part of the stationary phase. In the latter case, the chiral selector can be either covalently immobilized onto a solid support (bonded CSP, B-CSP) or physically adsorbed onto a conventional packing material, coated chiral stationary phase (C-CSP).In this chapter, a selection of CLEC applications with CMP- and C-CSP-based chiral systems is presented.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ácidos Carboxílicos/química , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Leucina , Ligantes , Modelos Moleculares , Ofloxacino/química , Ofloxacino/isolamento & purificação , Estereoisomerismo
2.
Amino Acids ; 51(4): 705-715, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30788600

RESUMO

Skin is made up of mainly collagen type I and its structure is stabilised by the formation of covalent immature and mature crosslinks. In this study, collagen immature crosslink hydroxylysinonorleucine (HLNL) was isolated from bovine skin in high purity using two sequential purification steps. These consisted of preparative fibrous cellulose and size exclusion chromatography. The purified crosslink was then analysed using tandem mass spectrometry and high-resolution nuclear magnetic resonance (NMR) spectroscopy. The mass of singly and doubly charged ions of HLNL was 292.1865 and 146.5970 m/z and their optimised fragmentation energy was 17 keV and 5 keV, respectively. The 13C NMR of HLNL showed a doubled-up peak at 67.84 and 67.91 ppm which corroborated a diastereomeric form of collagen immature crosslink HLNL and both are chiroptically indistinguishable. The chemical structure was fully resolved using 1H, 13C and DEPT-135 high-resolution NMR spectroscopy and compared with other previous studies. We also obtained for the first time the 2D NMR spectra COSY and HSQC of HLNL. We therefore suggested that collagen organization into specific fibrils' orientation may be affected by the different configuration of these diastereomers of HLNL.


Assuntos
Colágeno Tipo I/metabolismo , Reagentes para Ligações Cruzadas/química , Reagentes para Ligações Cruzadas/isolamento & purificação , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Pele/metabolismo , Animais , Bovinos , Reagentes para Ligações Cruzadas/metabolismo , Dipeptídeos/metabolismo , Imagem por Ressonância Magnética
3.
Chin J Nat Med ; 17(2): 149-154, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30797421

RESUMO

Two new isomeric modified tripeptides, aspergillamides C and D (compounds 1 and 2), together with fifteen known compounds (compounds 3-17), were obtained from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008. The structures of the new compounds, including absolute configurations, were determined by extensive analyses of spectroscopic data (NMR, MS, UV, and IR) and comparisons between the calculated and experimental electronic circular dichroism (ECD) spectra. Butyrolactone I (compound 11) exhibited strong inhibitory effects against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with the IC50 being 5.11 ± 0.53 µmol·L-1, and acted as a noncompetitive inhibitor based on kinetic analysis.


Assuntos
Aspergillus/química , Peptídeos/isolamento & purificação , Policetídeos/isolamento & purificação , Poríferos/microbiologia , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Animais , Técnicas de Química Analítica , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Dipeptídeos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Indóis/química , Indóis/isolamento & purificação , Indóis/farmacologia , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Policetídeos/química , Policetídeos/farmacologia , Proteínas Tirosina Fosfatases/química
4.
Int J Biol Macromol ; 126: 118-122, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30583004

RESUMO

A variety of physiological functions such as exopolysaccharide synthesis, antibiotic production, and primary metabolism are tightly controlled by quorum sensing in microorganisms. In this study, a marine-derived bacterium Sphingomonas sp. WG was found to possess a cyclo(L-Pro-L-Phe)-mediated quorum sensing mechanism. The cyclo(L-Pro-L-Phe) produced by Sphingomonas sp. WG functions as a signalling molecule in this quorum sensing system. It is the first attempt to characterize cyclic dipeptides as quorum sensing signalling molecules in Sphingomonas sp. and the results effectively make the classical quorum sensing theory more perfect. Furthermore, the supplementation with isolated cyclo(L-Pro-L-Phe) resulted in a 15% increase in the production of welan gum secreted by Sphingomonas sp. WG in the submerged fermentation. The data presented in this study will provide evidences for exploring the role of cyclic dipeptides in regulating the production of welan gum.


Assuntos
Dipeptídeos/metabolismo , Peptídeos Cíclicos/metabolismo , Polissacarídeos Bacterianos/biossíntese , Percepção de Quorum , Sphingomonas/metabolismo , Técnicas Biossensoriais , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Luminescência , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Transdução de Sinais
5.
Environ Sci Pollut Res Int ; 25(18): 17383-17392, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29654463

RESUMO

Tuna protein hydrolysate (TPH) was prepared by hydrolysis with Prolyve BS and fractionated by membranes process. The antioxidant activities of recovered peptide fractions were evaluated. Four novel antioxidant peptides that were isolated from nanofiltration retentate exhibited the highest antioxidant activity, using gel chromatography and reversed phase high-performance liquid chromatography. The amino acid sequences of isolated peptides were identified as Tyr-Glu-Asn-Gly-Gly (P2), Glu-Gly-Tyr-Pro-Trp-Asn (P4), Tyr-Ile-Val-Tyr-Pro-Gly (P7) and Trp-Gly-Asp-Ala-Gly-Gly-Tyr-Tyr (P8) with molecular weights of 538.46, 764.75, 710.78 and 887.85 Da, respectively. P2, P4, P7 and P8 exhibited good scavenging activities on hydroxyl radical (IC50 0.41, 0.327, 0.17 and 0.042 mg/ml), DPPH radical (IC50 0.666, 0.326, 0.451 and 0.377 mg/ml) and superoxide radical (IC50 0.536, 0.307, 0.357 and 0.115 mg/ml). P7 was effective against lipid peroxidation in the model system. The isolated peptides might be useful used as natural food additive in food industry and formulation of nutritional products.


Assuntos
Antioxidantes/química , Dipeptídeos/química , Oligopeptídeos/química , Peptídeos/química , Hidrolisados de Proteína/química , Sequência de Aminoácidos , Animais , Biomassa , Dipeptídeos/isolamento & purificação , Dipeptídeos/metabolismo , Hidrólise , Peroxidação de Lipídeos , Oligopeptídeos/isolamento & purificação , Peptídeos/isolamento & purificação , Peptídeos/metabolismo , Hidrolisados de Proteína/metabolismo , Superóxidos , Atum
6.
J Chromatogr A ; 1551: 69-74, 2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-29636178

RESUMO

The intermittently pressed tubing was introduced in type-I counter-current chromatographic system as the separation column to improve the separation performance in the present study. The separations were performed with two different solvent systems composed of 1-butanol-acetic acid-water (4:1:5, v/v) (BAW) and hexane-ethyl acetate-methanol-0.1 M HCl (1:1:1:1, v/v) (HEMW) using dipeptides and DNP-amino acids as test samples, respectively. The chromatographic performance was evaluated in terms of retention of the stationary phase (Sf), theoretical plate (N) and peak resolution (Rs). In general, the type-I planetary motion with the multilayer coil of non-modified standard tubing can yield the best separation at a low revolution speed of 200 rpm with lower flow rate. The present results with intermittently pressed tubing indicated that the performance was also optimal at the revolution speed of 200 rpm where the lower flow rate was more beneficial to retention of stationary phase and resolution. In the moderately hydrophobic two-phase solvent system composed of hexane-ethyl acetate-metanol-0.1 M hydrochloric acid (1:1:1:1, v/v), DNP-amino acids were separated with Rs at 1.67 and 1.47, respectively, with 12.66% of stationary phase retention at a flow rate of 0.25 ml/min. In the polar solvent system composed of 1-butanol-acetic acid-water (4:1:5, v/v), dipeptide samples were resolved with Rs at 2.18 and 18.75% of stationary phase retention at a flow rate of 0.25 ml/min. These results indicate that the present system substantially improves the separation efficiency of type-I counter-current chromatographic system.


Assuntos
Distribuição Contracorrente/métodos , Aminoácidos/química , Aminoácidos/isolamento & purificação , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Interações Hidrofóbicas e Hidrofílicas , Pressão , Solventes/química
7.
Bioorg Med Chem Lett ; 28(10): 1911-1914, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29631961

RESUMO

Callyspongiamides A (1) and B (2), two new sterol O-acyltransferase (SOAT) inhibitors, were isolated from the Indonesian marine sponge Callyspongia sp. together with a known congener, dysamide A (3). The structures of 1 and 2 were elucidated to be polychlorine-containing modified dipeptides based on their spectroscopic data. Compounds 1-3 inhibited both of the SOAT isozymes, SOAT1 and SOAT2, in cell-based and enzyme-based assays.


Assuntos
Callyspongia/química , Dipeptídeos/farmacologia , Inibidores Enzimáticos/farmacologia , Esterol O-Aciltransferase/antagonistas & inibidores , Animais , Callyspongia/metabolismo , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Ensaios Enzimáticos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Indonésia , Concentração Inibidora 50 , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Espectroscopia de Ressonância Magnética , Conformação Molecular , Esterol O-Aciltransferase/metabolismo
8.
J Antibiot (Tokyo) ; 71(8): 757-761, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29700424

RESUMO

A new metabolite, cyclic dipeptide, cis-(3S,8aS)-3-(3,4-dihydroxybenzyl)hexahydropyrrolo[1,2-a]pyrazine-1,4-dione, named JS-3 was isolated from Streptomyces sp. 8812 fermentation broth. Its chemical structure was established by means of spectroscopic analysis. A wide-range-screening study, which included inhibition assay of DD-carboxypeptidase/transpeptidase activity, determination of antibacterial, antifungal, and antiproliferative activities as well as free-radical scavenging was performed. To authors knowledge, this is the first isolation of such compound from natural sources and the first one from bacteria, Streptomyces.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Carboxipeptidases/antagonistas & inibidores , Dicetopiperazinas/farmacologia , Dipeptídeos/farmacologia , Peptidil Transferases/antagonistas & inibidores , Streptomyces/metabolismo , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Bactérias/efeitos dos fármacos , Dicetopiperazinas/isolamento & purificação , Dicetopiperazinas/metabolismo , Dipeptídeos/isolamento & purificação , Dipeptídeos/metabolismo , Fermentação , Fungos/efeitos dos fármacos
9.
Molecules ; 23(4)2018 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-29584684

RESUMO

A new lignanamide (1), lyciumamide K, together with four known analogues (2-5), was isolated from the root of Lycium yunnanense Kuang. Based on HR-ESI-MS, NMR spectral data and quantum chemistry ECD calculations, the structure of this new compound was confirmed, including its absolute configuration. Evaluation of the antioxidant activity of compounds 1-5 in the oxygen radical absorption capacity (ORAC) assay showed that they all exhibited significant antioxidant activities. Particularly, compound 1 showed the best activity with ORAC values (U/mol) of 7.90 ± 0.52. Thus, the new lignanamide may be a good source of bioavtive and protective compounds.


Assuntos
Depuradores de Radicais Livres/isolamento & purificação , Lignanas/isolamento & purificação , Lycium/química , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Dipeptídeos/farmacologia , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Lignanas/química , Lignanas/farmacologia , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química
10.
J Chromatogr A ; 1541: 47-51, 2018 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-29456156

RESUMO

In the present study, a novel model of type-I counter-current chromatography was developed to simplify the separation column manufacture and extend its application ranges. In this system, a multilayer coil was used as the separation column of type-I counter-current chromatography for the first time. The chromatographic performance of this apparatus was evaluated in terms of retention of the stationary phase (Sf), theoretical plate (N) and peak resolution (Rs) using dipeptides and DNP-amino acids as test samples with two classic solvent systems composed of 1-butanol-acetic acid-water (4:1:5, v/v) (BAW) and hexane-ethyl acetate-methanol-0.1 M HCl (1:1:1:1, v/v) (HEMW), respectively. The results indicated that the performance was optimal at the revolution speed of 200 rpm. The lower flow rate was more beneficial to retention of stationary phase and peak resolution. Over all results of our study revealed that the new type-I counter-current chromatography with a multilayer coil has a high application potential.


Assuntos
Técnicas de Química Analítica/instrumentação , Técnicas de Química Analítica/métodos , Distribuição Contracorrente/instrumentação , Aminoácidos/química , Aminoácidos/isolamento & purificação , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Solventes/química
11.
Molecules ; 23(1)2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29351264

RESUMO

Ralstonia solanacearum is a causative agent of bacterial wilt in many important crops throughout the world. How to control bacterial wilt caused by R. solanacearum is a major problem in agriculture. In this study, we aim to isolate the biocontrol agents that have high efficacy in the control of bacterial wilt. Three new bacterial strains with high antimicrobial activity against R. solanacearum GMI1000 were isolated and identified. Our results demonstrated that these bacteria could remarkably inhibit the disease index of host plant infected by R. solanacearum. It was indicated that strain GZ-34 (CCTCC No. M 2016353) showed an excellent protective effect to tomato under greenhouse conditions. Strain GZ-34 was characterized as Escherichia coli based on morphology, biochemistry, and 16S rRNA analysis. We identified that the main antimicrobial compounds produced by E. coli GZ-34 were cyclo(l-Pro-d-Ile) and cyclo(l-Pro-l-Phe) using electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) analysis. The two active compounds also interfered with the expression levels of some pathogenicity-contributors of R. solanacearum. Furthermore, cyclo(l-Pro-l-Phe) effectively inhibited spore formation of Magnaporthe grisea, which is a vital pathogenesis process of the fungal pathogen, suggesting cyclic dipeptides from E. coli are promising potential antimicrobial agents with broad-spectrum activity to kill pathogens or interfere with their pathogenesis.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antibiose , Dipeptídeos/química , Escherichia coli/metabolismo , Peptídeos Cíclicos/química , Ralstonia solanacearum/efeitos dos fármacos , Anti-Infecciosos/isolamento & purificação , Dipeptídeos/isolamento & purificação , Dipeptídeos/farmacologia , Escherichia coli/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Peptídeos Cíclicos/isolamento & purificação , Peptídeos Cíclicos/farmacologia , Plantas/microbiologia , Microbiologia do Solo , Espectrometria de Massas por Ionização por Electrospray
12.
Chirality ; 30(4): 491-497, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29315810

RESUMO

The enantiomeric resolution of DL-alanine-DL-tryptophan dipeptide is described on amylose stationary phase. The eluent used was CH3 OH─CH3 COONH4 (10mM)─CH3 CN (50: 40, 10) at 0.8-mL/min flow, 230-nm detection, 25-minute run time, and 25°C ± 1°C temperature. The chiral phase was amylose [AmyCoat RP (15 cm × 0.46 cm × 5 micron)]. The magnitudes of the retention factors (k) were 2.71, 3.52, 5.11, and 7.75. The magnitudes of separation factor (α) were 1.19, 1.57, and 1.51 while the resolution factors (Rs) were 3.25, 14.84, and 15.76. The limits of detection and quantitation were of 2.5 to 5.4 and 12.8 to 27.5 µg/mL. The enantiomeric resolution is controlled by hydrogen, hydrophobic, π-π, steric, etc interactions. The elution order of the enantiomer was supported by the modeling data. The described method is fast, reproducible, precise, and selective, which can be used successfully for evaluating the enantiomers of the reported dipeptide.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dipeptídeos/química , Alanina/química , Amilose/química , Dipeptídeos/isolamento & purificação , Hidrogênio/química , Limite de Detecção , Reprodutibilidade dos Testes , Estereoisomerismo , Triptofano/química
13.
Molecules ; 23(1)2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29303958

RESUMO

The gonad of jellyfish (RhopilemaesculentumKishinouye), containing high protein content with a rich amino acid composition, is suitable for the preparation of bioactive peptides. Jellyfish gonad was hydrolysed with neutral protease to obtain jellyfish gonad protein hydrolysate (JGPH), which was then purified sequentially by ultrafiltration, gel filtration chromatography, and RP-HPLC. The peptides were characterized with HPLC-MS/MS. One peptide with amino acid sequence Ser-Tyr (SY) was identified and synthesized, which showed good ACE inhibitory and antioxidant activity. The IC50 of this peptide on DPPH, ·OH, super oxygen anion scavenging activities, and ACE inhibitory activity are 84.623 µM, 1177.632 µM, 456.663 µM, and 1164.179 µM, respectively. The anchor in the binding site of SY and ACE C-domain (ACE-C) was obtained by molecular simulations. The results showed that the dipeptide purified from jellyfish gonad protein hydrolysates can be used as functional food material and is helpful in the study of antioxidant and inhibition of ACE.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Dipeptídeos/química , Depuradores de Radicais Livres/química , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Compostos de Bifenilo/química , Domínio Catalítico , Cromatografia em Gel , Dipeptídeos/isolamento & purificação , Depuradores de Radicais Livres/isolamento & purificação , Gônadas/química , Hidrólise , Simulação de Acoplamento Molecular , Peptidil Dipeptidase A/química , Picratos/química , Ligação Proteica , Cifozoários/química , Superóxidos/química
14.
Nat Prod Res ; 32(19): 2260-2267, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29171293

RESUMO

The secondary metabolites of Xylaria cf. cubensis SWUF08-86 fungus were investigated, and the chromatographic separation of the crude extracts yielded seventeen compounds. The structure elucidation by spectroscopic analysis including 1D and 2D NMR and the comparison of these data with literature, along with HREIMS spectrometry, revealed one new amino amidine derivative (1), together with five known simple cyclic dipeptide analogs, diketopiperazines (2-6) and eleven other known compounds, including one hemi-cycline (10), three aromatic derivatives (11-13), one sesquiterpene (14) and three sterols (15-17). The isolated compounds were screened for anticancer and anti-pathogenic bacterial and fungal activities. Based on this work, Xylaria cf. cubensis SWUF08-86 has proven to be a diverse secondary metabolites producer.


Assuntos
Amidinas/isolamento & purificação , Xylariales/química , Amidinas/química , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Xylariales/metabolismo
15.
Mol Med Rep ; 17(3): 4120-4130, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29286166

RESUMO

Fatigue is a common and serious health problem, and various dietary interventions have previously been employed to ameliorate fatigue. The aim of the current study was to investigate the anti­fatigue effects of Danish porcine placenta (DPP) and its major dipeptides, including leucine­glycine (LG) and glycine­leucine (GL). The anti­fatigue effects of orally administered DPP, LG and GL were determined using a treadmill exercise test and a forced swimming test (FST) in mice. Additionally, the anti­inflammatory effects of DPP, LG and GL were investigated in activated splenocytes. The results demonstrated that oral treatment of mice with DPP, LG and GL increased the time to exhaustion during treadmill exercise. Furthermore, DPP, LG and GL enhanced the levels of dopamine, brain­derived neurotrophic factor and phosphorylated-extracellular signal­regulated kinase in the brains of mice with treadmill exercise­induced exhaustive fatigue, and decreased levels of certain proinflammatory cytokines in the serum and spleen, as determined by ELISA and western blot analysis. Following treadmill exercise, commercial kits were employed to demonstrate that DPP, LG and GL reduced the levels of lactate dehydrogenase, lactate, creatine kinase, blood urea nitrogen, alanine transaminase and aspartate transaminase in the muscle and/or serum of mice. In addition, DPP, LG and GL enhanced the muscle and liver glycogen levels, catalase activity in the liver and serum superoxide dismutase activity. DPP, LG and GL also increased the proliferation of splenocytes and inhibited proinflammatory cytokine production by reducing the activation of caspase­1 and nuclear factor­κB in activated splenocytes, as determined by MTT assays, ELISA and western blotting, respectively. Furthermore, DPP, LG and GL reduced immobility time in the FST in mice. In conclusion, DPP may limit intensive exercise­induced fatigue by increasing dopaminergic systems and inhibiting inflammatory responses.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Dipeptídeos/farmacologia , Agonistas de Dopamina/farmacologia , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Fadiga/prevenção & controle , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Caspase 1/genética , Caspase 1/metabolismo , Estimulantes do Sistema Nervoso Central/isolamento & purificação , Dipeptídeos/isolamento & purificação , Agonistas de Dopamina/isolamento & purificação , Neurônios Dopaminérgicos/metabolismo , Teste de Esforço , Fadiga/genética , Fadiga/metabolismo , Fadiga/fisiopatologia , Feminino , Regulação da Expressão Gênica , Masculino , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Condicionamento Físico Animal/métodos , Esforço Físico/efeitos dos fármacos , Placenta/química , Gravidez , Suínos
16.
Nat Prod Res ; 32(8): 972-976, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28862058

RESUMO

Three cyclic dipeptides (1-3), including one new compound (1) were isolated from cultures of the basidiomycetes Coprinus plicatilis. Their structures were elucidated by spectroscopic methods, including extensive 2D NMR techniques. At the same time, all compounds were tested for their cytotoxicities against five human cancer cell lines.


Assuntos
Antineoplásicos/farmacologia , Coprinus/química , Dipeptídeos/farmacologia , Peptídeos Cíclicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação
17.
Bioorg Med Chem ; 25(24): 6614-6622, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29153548

RESUMO

A new trichodermamide-like alkaloid, N-Me-trichodermamide B (compound 1), was isolated from a marine fungus Penicillium janthinellum HDN13-309. The structure and absolute configuration of compound 1 were determined by extensive NMR analysis and the modified Mosher's method. This new alkaloid exhibited cellular protection from the H2O2-induced oxidative damage, and the mechanism study revealed that this antioxidant activity was regulated through Nrf2-mediated signaling pathway in HaCaT human keratinocytes. In addition, the inhibitor of p38 abrogated compound 1-induced phosphorylation of p38, up-expression of HO-1, and the nuclear localization of Nrf2. As a result, it suggested that this new alkaloid-induced antioxidant signaling pathway might be initiated through activation of p38.


Assuntos
Antioxidantes/farmacologia , Dipeptídeos/farmacologia , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Penicillium/química , Transdução de Sinais/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Relação Estrutura-Atividade
18.
Nutr Res ; 46: 22-30, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29173648

RESUMO

Identification of bioactive milk peptides could improve food technology through improved selection of food supplements with a focus on antihypertensive properties. We hypothesized that angiotensin I-converting enzyme (ACE) inhibitory activities of milk di- and tripeptides could be predicted using 3-dimensional quantitative structure activity relationship methods and that these activities could be explained through evaluation of structural features (hydrogen bond donor/acceptor, hydrophobic, steric, and electrostatic) that are responsible for this bioactivity. We aimed to build comparative molecular field analysis (CoMFA) models combined with in silico digestion to predict the peptide sequences released from enzymatic digestion and to evaluate peptides without experimental data. Furthermore, molecular docking simulation was performed with the aim to evaluate structural features. Molecular docking simulations revealed that the most potent inhibitory peptides contain hydrophobic amino acids that enter deep into the hydrophobic pocket of the ACE active site and make interactions with its residues. CoMFA results point out favorable steric interactions and electronegativity at the C-terminus of the milk dipeptides. The CoMFA model appears to favor electropositive amino acids at the second place in tripeptides and electronegative interaction with Tyr520. Furthermore, predicted values of ACE inhibitory activity of dipeptides obtained by peptide cutter are relatively high, which recommend them for application as functional food supplements and natural alternatives to ACE inhibitory drugs. This research suggests that obtained 3-dimensional quantitative structure activity relationship models are able to successfully identify milk-derived di- and tripeptides that have significant antihypertensive activity and provide information for screening and design of novel ACE inhibitors that could be used as supplements in human nutrition.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/metabolismo , Dipeptídeos/metabolismo , Sistemas Especialistas , Proteínas do Leite/metabolismo , Modelos Moleculares , Oligopeptídeos/metabolismo , Peptidil Dipeptidase A/química , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Anti-Hipertensivos/química , Anti-Hipertensivos/isolamento & purificação , Anti-Hipertensivos/metabolismo , Sítios de Ligação , Domínio Catalítico , Bovinos , Biologia Computacional , Suplementos Nutricionais , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Proteínas do Leite/química , Proteínas do Leite/isolamento & purificação , Simulação de Acoplamento Molecular , Oligopeptídeos/química , Oligopeptídeos/isolamento & purificação , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/isolamento & purificação , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Conformação Proteica , Proteólise , Relação Quantitativa Estrutura-Atividade
19.
J Nat Prod ; 80(10): 2845-2849, 2017 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-29016113

RESUMO

Direct comparison of authentic ciliatamide A with four synthetic isomers (1-4) by means of NMR and chiral-phase HPLC revealed that ciliatamide A possesses the 12R (d-N-MePhe residue) and 22S (l-Lys residue) configurations, which were not identical with either our previous assignment or those proposed by others through total synthesis. The absolute configuration of the methionine sulfoxide residue in ciliatamide D was also revised to be d.


Assuntos
Dipeptídeos/química , Lipopeptídeos/química , Poríferos/química , Animais , Cromatografia Líquida de Alta Pressão , Dipeptídeos/isolamento & purificação , Lipopeptídeos/isolamento & purificação , Biologia Marinha , Estrutura Molecular , Oxirredução , Estereoisomerismo
20.
Bioconjug Chem ; 28(10): 2560-2568, 2017 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-28846388

RESUMO

Water-soluble polyisocyanopeptides (PICs) are a new class of synthetic polymers that mimic natural protein-based filaments. Their unique semiflexible properties combined with a length of several hundred nanometers have recently enabled a number of biomedical applications ranging from tissue engineering to cancer immunotherapy. One crucial step toward the further development of PICs for these applications is the efficient and controlled synthesis and purification of PIC-biomolecule conjugates. Considering the large size of PICs and the biomolecules to be conjugated, conjugation reactions do usually not proceed to completion due to steric effects. As a consequence, purification of the reaction mixture is necessary to separate the obtained bioconjugates from unreacted biomolecules. As a direct result of the semiflexible nature of PICs, standard polymer and protein purification methods based on molecular weight have not been successful. Here, we introduce a new affinity-based purification method utilizing biotin as an affinity tag. PICs decorated with a controlled and tunable density of biotin molecules (biotinPICs) were efficiently bound to and eluted from a monoavidin resin in buffered aqueous solution. Using these biotinPICs, two different protein conjugates were synthesized, one carrying the enzyme alkaline phosphatase (PhoA) and the other T-cell activating anti-CD3 antibodies. The resulting biotinPIC-protein conjugates were successfully obtained in high purity (>90%) and without any loss of protein activity. The high purity greatly simplifies the analysis of biotinPIC bioconjugates, such as the determination of the average number of biomolecules conjugated per biotinPIC chain. Most importantly, it allows for the direct and straightforward application of the obtained bioconjugates in the desired applications. The new method developed may further be adapted for the purification of other advanced bioconjugates that are difficult to obtain in high purity with the available standard methods.


Assuntos
Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Nitrilos/química , Nitrilos/isolamento & purificação , Fosfatase Alcalina/metabolismo , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Avidina/química , Avidina/metabolismo , Biotina/química , Complexo CD3/imunologia , Escherichia coli/enzimologia , Humanos , Imunoconjugados/química , Imunoconjugados/isolamento & purificação , Solubilidade , Água/química
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