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1.
Molecules ; 25(6)2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32183050

RESUMO

Serious environmental and human health problems caused by the abuse of antibiotics have attracted worldwide concern. Recently, metal-organic frameworks (MOFs) with high porosity have drawn wide attention for their effects in the adsorption and removal of pollutants from complex matrices. Herein, a high-stable metal organic framework (MOF), i.e., ((ZnCl2)3(L)2·DMF)n, where L=1,3,5-tris((pyridin-4-ylthio)methyl)benzene), MOF 1, was applied to adsorb and remove tetracycline from sewage and dairy products. The results showed that MOF 1 exhibited a strong performance in the adsorption of tetracycline. The effects of initial pH values, adsorbent dose, contact time and ionic strength of the adsorption performance of MOF 1 were investigated. The adsorption kinetics best fit the pseudo-second order model, and the adsorption isotherms matched the Langmuir adsorption model well. It was indicated that both chemical adsorption and physical adsorption play an important role in the adsorption process, and the adsorption of tetracycline was homogeneous and occurred on a monolayer on the surface of MOF 1. Additionally, the stability of MOF 1 and the details of the adsorption mechanism were also investigated. Thus, this study provides a new candidate for the application of MOFs-based adsorbents in the removal of antibiotics from sewage and dairy products.

2.
Anal Chem ; 92(3): 2672-2679, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31898456

RESUMO

Sulfur-containing species (SCS), especially sulfur dioxide-relevant species, play an essential role in ecological balance. Owing to the intrinsically labile and mobile characteristics of SCS, it is still considered to be an insurmountable challenge for multiplexed tracking dynamics of SCS with distinct molecular structure, valence state, and condensed state. To address this key problem, we proposed herein alternative versatile single-molecule sensors (VSMs) that intramolecularly integrate high affinity target-guided multiple recognition units into a single sensory molecule, clarified as molecular Nezha available in triplexed responses to gaseous sulfur dioxide, liquid sulfur trioxide, and aqueous bisulfite through ubiquitous charge transfer and nucleophilic addition. High-performance molecular Nezha remarkably facilitated promising applications in a quantitative visualization of SCS on lab-on-paper and tracking the dynamics transformation of SCS as well comprehensive evaluation of multiphase adsorption science of SCS on an advanced Zeolitic imidazolate framework-8 (ZIF-8).

3.
Eur J Med Chem ; 185: 111844, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31706640

RESUMO

Lung cancer is one of the most malignant tumors with the highest morbidity and mortality. Most of them are non-small cell lung cancer (NSCLC). KRASG12C gene mutation is an important driving factor for NSCLC. However, the development of high-affinity inhibitors targeting KRASG12C mutants remains a daunting challenge. Here, we report the design and development of a series of hydrocarbon-stapled peptides containing d-amino acids to mimic the alpha helix of SOS1. D-hydrocarbon-stapled peptides maintain good alpha helix structure and bind to KRASG12C with high affinity. Subsequent anti-proliferation experiments indicated that D-hydrocarbon-stapled peptide 5 inhibited the proliferation of NSCLC H358 cells carrying KRASG12C. However, it showed no significant anti-proliferative effect on KRASG12S-positive A549 cells, suggesting that peptide 5 selectively inhibits KRASG12C-driven tumor cells. D-hydrocarbon-stapled peptide 5 could also cause the cell cycle of H358 cells to arrest in the G2/M phase and induce apoptosis. No significant cell arrest and apoptosis were observed in A549 cells treated by peptide 5. In summary, the introduction of d-amino acids could improve the affinity and cell selectivity of hydrocarbon peptides. We hope that peptides containing D-form amino acids can provide strategies for further optimization of the KRASG12C/SOS1 inhibitor.


Assuntos
Aminoácidos/farmacologia , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Peptídeos/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteína SOS1/antagonistas & inibidores , Células A549 , Aminoácidos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Estrutura Molecular , Peptídeos/síntese química , Peptídeos/química , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteína SOS1/metabolismo , Relação Estrutura-Atividade
4.
Dalton Trans ; 48(48): 17800-17809, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31769766

RESUMO

Hg2+ is highly toxic and hazardous and widely found in polluted water. To remove mercury ions from wastewater, there is an urgent need to investigate and develop new adsorbents. Herein, we synthesized three novel thioether-based metal-organic frameworks (MOFs) through a facile diffusion method or a solvothermal strategy, i.e. [(ZnCl2)3(L1)2·χ(solvent)]n (1), [(Cu2I3O2)4(CH4N0.5)4(L1)4(DMA)4·3(H2O)·χ(solvent)]n (2) and [(CuBr2)2(L2)2 CH3CN·χ(solvent)]n (3), where L1 = 1,3,5-tris((pyridin-4-ylthio)methyl)benzene and L2 = 2,4,6-trimethoxy-1,3,5-tris((pyridin-4-ylthio)methyl)benzene. The obtained thioether-based MOFs were characterized by single-crystal X-ray diffraction, Fourier transform infrared spectroscopy, elemental analysis and thermogravimetric analysis. Further studies revealed that they could remove Hg2+ from water. They have high adsorptivity (up to 362 mg g-1) and are highly efficient in removing Hg2+ (up to 95%). Besides, these MOFs can be recycled and can selectively remove Hg2+ from water in the presence of other metal ions. Consequently, these MOFs are highly promising candidates for the selective absorption and removal of mercury ions from water.

5.
Anal Chem ; 91(23): 14943-14950, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31714063

RESUMO

We show how the macrocyclic host cucurbit[8]uril (CB[8]) and a fluorescent dye form a biosensing ensemble while its cavity simultaneously traps tryptophan, the upstream substrate of IDO1 enzymes, therefore providing a label-free method to monitor the activity of IDO1 in real time. Incubation of malignant HeLa and HepG2 cells overexpressing IDO1 with the associative biosensor resulted in its spontaneous uptake and a fluorescence switch-on response in situ, which can be traced to the displacement of tryptophan from CB[8] upon IDO1-catalyzed oxidation. The results, for the first time, establish a supramolecular sensing concept for the detection of intracellular enzymatic activity in live cells, thus allowing direct cell-based analysis and inhibitor screening compatible with commercial instruments including microplate reader, fluorescent microscopy, and flow cytometry.

6.
J Chem Phys ; 151(18): 184703, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31731868

RESUMO

Ceria has been widely applied as a support in heterogeneous catalysis due to its unique capability to store and release oxygen. As a typical inverse model catalyst, a ceria/Pt(111) system has attracted much attention due to its strong metal-oxide interaction. The structural and electronic properties of the ceria/Pt(111) system can be effectively modified by the introduction of alien K and Rh atoms. Here, the K- and Rh-modified ceria/Pt(111) inverse model catalysts have been investigated with high resolution scanning tunneling microscopy and apparent local work function measurement. The experimental results indicate that the K atoms prefer to occupy the top sites of the stoichiometric ceria, while the Rh atoms are prone to stay at the electron-rich ceria island edges. The K and Rh atoms act as an electron donor and acceptor on ceria/Pt(111), respectively. Such a study on the modification of the ceria-based catalysts should help understand strong metal-oxide interaction in heterogeneous catalysis at the atomic level.

7.
Molecules ; 24(17)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31480625

RESUMO

Tubulin inhibitors have been considered as potential drugs for cancer therapy. However, their drug resistance and serious side-effects are the main reasons for clinical treatment failure. Therefore, there is still an urgent need to develop effective therapeutic drugs. Herein, a structure-based pharmacophore model was developed based on the co-crystallized structures of the tubulin with a high resolution. The model including one hydrogen-bond acceptor feature, two aromatic features, and one hydrophobic feature was further validated using the Gunner-Henry score method. Virtual screening was performed by an integrated protocol that combines drug-likeness analysis, pharmacophore mapping, and molecular docking approaches. Finally, five hits were selected for biological evaluation. The results indicated that all these hits at the concentration of 40 µM showed an inhibition of more than 50% against five human tumor cells (MCF-7, U87MG, HCT-116, MDA-MB-231, and HepG2). Particularly, hit 1 effectively inhibited the proliferation of these tumor cells, with inhibition rates of more than 80%. The results of tubulin polymerization and colchicine-site competition assays suggested that hit 1 significantly inhibited tubulin polymerization by binding to the colchicine site. Thus, hit 1 could be used as a potential chemotherapeutic agent for cancer treatment. This work also demonstrated the potential of our screening protocol to identify biologically active compounds.


Assuntos
Antineoplásicos/farmacologia , Desenho de Drogas , Avaliação Pré-Clínica de Medicamentos , Relação Quantitativa Estrutura-Atividade , Moduladores de Tubulina/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colchicina/metabolismo , Humanos , Ligantes , Modelos Moleculares , Polimerização , Tubulina (Proteína)/metabolismo
8.
Sensors (Basel) ; 19(9)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035410

RESUMO

In this paper, a multi-robot persistent coverage of the region of interest is considered, where persistent coverage and cooperative coverage are addressed simultaneously. Previous works have mainly concentrated on the paths that allow for repeated coverage, but ignored the coverage period requirements of each sub-region. In contrast, this paper presents a combinatorial approach for path planning, which aims to cover mission domains with different task periods while guaranteeing both obstacle avoidance and minimizing the number of robots used. The algorithm first deploys the sensors in the region to satisfy coverage requirements with minimum cost. Then it solves the travelling salesman problem to obtain the frame of the closed path. Finally, the approach partitions the closed path into the fewest segments under the coverage period constraints, and it generates the closed route for each robot on the basis of portioned segments of the closed path. Therefore, each robot can circumnavigate one closed route to cover the different task areas completely and persistently. The numerical simulations show that the proposed approach is feasible to implement the cooperative coverage in consideration of obstacles and coverage period constraints, and the number of robots used is also minimized.

9.
Adv Healthc Mater ; 8(13): e1900174, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30990966

RESUMO

Nanosystems responsive to tumor-specific enzymes are considered as a highly attractive approach to intracellular drug release for targeted cancer therapy. Mesoporous silica nanoparticles are capped with tryptophan-mediated cucurbit[8]uril complex with Fe3 O4 to minimize the premature drug leakage while being able to deliver the payload on demand at the target tissue. The supramolecular interaction between tryptophan and cucurbit[8]uril is disrupted in the presence of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme (abundant in the tumor intracellular microenvironment), which catalyzes the metabolism of tryptophan into N-formylkynurenine, resulting in the disassembly of the "gate-keeper" of the nanocarriers and intracellular release of therapeutics exclusively in tumor cells. The drug release from the nanocarrier with high selectivity to overexpressed IDO1 enzyme induces significant cytotoxicity against HepG2 cells in vitro, as well as the superior antitumor effects in vivo. This robust supramolecular nanosystem with sophisticated structure and property provides a promising platform for intracellular drug release targeting the intrinsic microenvironmental enzyme inside the tumor cells.

10.
Fitoterapia ; 134: 135-140, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30771464

RESUMO

The determination of the absolute configuration of natural products still faces many challenges, especially the active pharmaceutical ingredient which is trace, oily and novel structures. Currently, NMR requires chiral reagents in determining the absolute configuration; ECD involves theoretical calculations and requires chromophores. In this study, the absolute configuration of asarinin had successfully identified by using synchrotron radiation with crystalline sponge method and combining MS with NMR. This method could identifying the crystal structure of trace amorphous substances, resolving the problem of absolute configuration of multi-chiral central compounds, and hopefully providing a new idea and approach for structural elucidation of natural products.


Assuntos
Asarum/química , Produtos Biológicos/química , Dioxóis/química , Lignanas/química , Síncrotrons , China , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Modelos Moleculares , Compostos Fitoquímicos/química
11.
Biochim Biophys Acta Biomembr ; 1861(4): 835-844, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30658057

RESUMO

Defensins are a family of cationic antimicrobial peptides of innate immunity with immunomodulatory properties. The prototypic human α-defensins, also known as human neutrophil peptides 1-3 or HNP1-3, are extensively studied for their structure, function and mechanisms of action, yet little is known about HNP4 - the much less abundant "distant cousin" of HNP1-3. Here we report a systematic mutational analysis of HNP4 with respect to its antibacterial activity against E. coli and S. aureus, inhibitory activity against anthrax lethal factor (LF), and binding activity for LF and HIV-1 gp120. Except for nine conserved and structurally important residues (6xCys, 1xArg, 1xGlu and 1xGly), the remaining 24 residues of HNP4 were each individually mutated to Ala. The crystal structures of G23A-HNP4 and T27A-HNP4 were determined, both exhibiting a disulfide-stabilized canonical α-defensin dimer identical to wild-type HNP4. Unlike HNP1-3, HNP4 preferentially killed the Gram-negative bacterium, a property largely attributable to three clustered cationic residues Arg10, Arg11 and Arg15. The cationic cluster was also important for HNP4 killing of S. aureus, inhibition of LF and binding to LF and gp120. However, F26A, while functionally inconsequential for E. coli killing, was far more deleterious than any other mutations. Similarly, N-methylation of Leu20 to destabilize the HNP4 dimer had little effect on E. coli killing, but significantly reduced the ability of HNP4 to kill S. aureus, inhibit LF, and bind to LF and gp120. Our findings unveil the molecular determinants of HNP4 function, completing the atlas of structure and function relationships for all human neutrophil α-defensins.


Assuntos
Antibacterianos , Escherichia coli/crescimento & desenvolvimento , Mutação , Multimerização Proteica , Staphylococcus aureus/crescimento & desenvolvimento , alfa-Defensinas , Substituição de Aminoácidos , Antibacterianos/química , Antibacterianos/farmacologia , Antígenos de Bactérias/química , Toxinas Bacterianas/antagonistas & inibidores , Toxinas Bacterianas/química , Humanos , Relação Estrutura-Atividade , alfa-Defensinas/química , alfa-Defensinas/genética , alfa-Defensinas/farmacologia
12.
Free Radic Biol Med ; 134: 288-303, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30615919

RESUMO

Parkinson's disease (PD) is the second most common aging-related neurodegenerative disease worldwide. Oxidative stress and neuroinflammation are critical events in the degeneration of dopaminergic neurons in PD. In this study, we found that DDO-7263, a novel Nrf2-ARE activator reported by us, has ideal therapeutic effects on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease in mice. DDO-7263 improved the behavioral abnormalities induced by MPTP in mice, significantly attenuated chemically induced dopaminergic neuron loss of tyrosine hydroxylase (TH) in the substantia nigra (SN) and striatum of the mouse brain and inhibited the secretion of inflammatory factors. In addition, DDO-7263 protected PC12 neurons from H2O2-induced oxidative damage. The neuroprotective effects of DDO-7263 were confirmed both in vitro and in vivo models. Further studies showed that the neuroprotective effect of DDO-7263 was mediated by the activation of Nrf2-ARE signaling pathway and the inhibition of NLRP3 inflammasome activation. DDO-7263 induced NLRP3 inflammasome inhibition is dependent on Nrf2 activation. This conclusion was also verified in THP-1-derived macrophages (THP-Ms). DDO-7263 significantly inhibited NLRP3 activation, cleaved caspase-1 production and IL-1ß protein expression in ATP-LPS-exposed THP-Ms cells. The pharmacokinetic parameters and tissue distribution results indicated that DDO-7263 has a brain tissue targeting function. All these lines of evidence show that DDO-7263 has ideal therapeutic effects on neurodegenerative diseases such as PD.

13.
Adv Healthc Mater ; 8(2): e1801458, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30548830

RESUMO

The fabrication, characterization, and therapy efficiency of a noncovalent-bonded hydrogel network, which is assembled by utilizing cucurbit[7]uril as a supramolecular linker to "stick" superparamagnetic γ-Fe2 O3 nanoparticles onto the polymer backbone of catechol-functionalized chitosan are described. The unique barrel-shaped structure of cucurbit[7]uril not only facilitates host-guest recognition with the catechol derivatives, but also forms robust electrostatic interactions between its carbonyl portals and the γ-Fe2 O3 nanoparticles in a supramolecular manner, which leaves the physical and chemical properties of the nanoparticles intact. The γ-Fe2 O3 nanoparticles display vibrational movement and heat generation under an alternating magnetic field, endowing the formed hybrid supramolecular hydrogel with both thermo- and chemotherapy modalities, which are demonstrated both in vitro and in vivo. Here, a facile strategy is introduced to construct noncovalent interactions between a polymer matrix and the incorporated nanoparticles, which is amendable to a wide range of biomedical and industrial applications.

15.
Eur J Med Chem ; 157: 1376-1394, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30196061

RESUMO

The antioxidant function induced by Nrf2 protects the liver from damage. We found a novel Nrf2 activator named compound 25 via structural modification of compound 1 we previously reported. In vitro, compound 25 induced Nrf2 transport into the nucleus and protected hepatocyte L02 cells from APAP-induced cytotoxicity via activating the Nrf2-ARE signaling pathway. In vivo, 25 exhibited therapeutic effects in a mouse model of acute liver injury induced by acetaminophen (APAP) by up-regulating Nrf2-dependent antioxidases and down-regulating liver injury markers in serum. Together, these results indicated that 25 is a potent Nrf2/ARE activator both in vitro and in vivo. The drug-like properties of compound 25 further revealed its potential for development as a therapeutic drug against acute liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Oxidiazóis/farmacologia , Acetaminofen , Linhagem Celular , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/química , Relação Estrutura-Atividade
16.
Anal Sci ; 34(9): 1093-1098, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30197378

RESUMO

Quantitative nuclear magnetic resonance (qNMR) has emerged as an easy, rapid and reproducible method for various pharmaceuticals. In the current study, a general qNMR approach for calibrating the purity of the thiopeptcin reference standard (also known as nocathiacin I) was developed using sulfadoxine as an internal standard. Experimental conditions, such as the relaxation delay time and number of scans, were systematically optimized, and the method was validated with different analytical parameters, including selectivity, stability, linearity, precision and robustness. To examine the reliability and feasibility of the present qNMR method, there was no significant difference in the quantification of this complex cyclic peptide compared to the mass balance method. The present study further exemplified that qNMR is a reliable and valuable approach for the assessing of absolute purity of small-molecule pharmaceuticals, which provides a useful tool for drug discovery and development.


Assuntos
Peptídeos/análise , Peptídeos e Proteínas de Sinalização Intercelular , Conformação Molecular , Peptídeos/normas , Espectroscopia de Prótons por Ressonância Magnética/normas , Padrões de Referência
17.
Org Biomol Chem ; 16(28): 5097-5101, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-29972388

RESUMO

A counterintuitive freezing-induced peptide ligation was discovered during the total synthesis of human interferon-ε (hIFN-ε) which blocks HIV infection through unique mechanisms. The successful synthesis of hIFN-ε (187 amino acids) in this research laid the foundation for related anti-AIDS drug development. Moreover, alanine mutation based on sequence alignment to solve the maldistribution of the ligation site and freezing-induced dominant conformation that facilitates peptide ligation are expected to be helpful for the synthesis of macrobiomolecules.


Assuntos
Descoberta de Drogas , Congelamento , Interferons/síntese química , Interferons/metabolismo , Peptídeos/metabolismo , Sequência de Aminoácidos , Animais , Humanos , Interferons/química , Modelos Moleculares , Conformação Proteica
18.
Oxid Med Cell Longev ; 2018: 3271617, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29887940

RESUMO

Ulcerative colitis (UC) is a common inflammatory bowel disease that can destroy the integrity of the colon and increase the risk of colorectal cancer. Oxidative stress is one of the critical pathogenic factors for UC, further impairing the entire affected colon. The Nrf2-ARE signaling pathway plays an important role in counteracting oxidative and electrophilic stress. Activation of the Nrf2-ARE pathway provides an indispensable defense mechanism for the treatment of UC. In this study, we identified a novel effective Nrf2 activator, DDO7232, which showed protective effects on NCM460 cells and therapeutic effects on DSS-induced colitis in mice. Mechanistic studies indicated that the Nrf2-ARE-inducing activity of DDO7232 was based on the activation of the ERK1/2 phosphorylation. The phosphorylation of Nrf2 Ser40 by p-ERK triggered the transport of Nrf2 into the nucleus and drove the expression of Nrf2-dependent antioxidant proteins. These results not only revealed the antioxidant mechanisms of DDO7232 but also provided an effective therapeutic option for the treatment of UC.


Assuntos
Colite/induzido quimicamente , Sistema de Sinalização das MAP Quinases/genética , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Fosforilação , Transdução de Sinais , Transfecção
19.
Bioorg Med Chem ; 26(12): 3429-3437, 2018 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-29807699

RESUMO

Polo-like kinase 1 (Plk1) is an anti-cancer target due to its critical role in mitotic progression. A growing body of evidence has documented that Peptide-Plk1 inhibitors showed high Plk1 binding affinity. However, phosphopeptides-Plk1 inhibitors showed poor cell membranes permeability, which limits their clinical applications. In current study, nine candidate phosphopeptides consisting of non-natural amino acids were rationally designed and then successfully synthesized using an Fmoc-solid phase peptide synthesis (SPPS) strategy. Moreover, the binding affinities and selectivity were evaluated via fluorescence polarization (FP) assay. The results confirmed that the most promising phosphopeptide 6 bound to Plk1 PBD with the IC50 of 38.99 nM, which was approximately 600-fold selectivity over Plk3 PBD (IC50 = 25.44 µM) and nearly no binding to Plk2 PBD. Furthermore the intracellular activities and the cell membrane permeability of phosphopeptide 6 were evalutated. Phosphopeptide 6 demonstrated appropriate cell membrane permeability and arrested HeLa cells cycle in G2/M phase by regulating CyclinB1-CDK1. Further, phosphopeptide 6 showed typical apoptotic morphology and induced caspase-dependent apoptosis. In conclusion, we expect our discovery can provide new insights into the further optimization of Plk1 PBD inhibitors.


Assuntos
Proteínas de Ciclo Celular/antagonistas & inibidores , Desenho de Drogas , Fosfopeptídeos/química , Inibidores de Proteínas Quinases/síntese química , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Sequência de Aminoácidos , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Proteínas de Ciclo Celular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Células HeLa , Humanos , Fosfopeptídeos/metabolismo , Fosfopeptídeos/farmacologia , Ligação Proteica , Domínios Proteicos , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo
20.
Magn Reson Chem ; 56(1): 37-45, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28921691

RESUMO

Quantitative nuclear magnetic resonance (qNMR) is a well-established technique in quantitative analysis. We presented a validated 1 H-qNMR method for assay of octreotide acetate, a kind of cyclic octopeptide. Deuterium oxide was used to remove the undesired exchangeable peaks, which was referred to as proton exchange, in order to make the quantitative signals isolated in the crowded spectrum of the peptide and ensure precise quantitative analysis. Gemcitabine hydrochloride was chosen as the suitable internal standard. Experimental conditions, including relaxation delay time, the numbers of scans, and pulse angle, were optimized first. Then method validation was carried out in terms of selectivity, stability, linearity, precision, and robustness. The assay result was compared with that by means of high performance liquid chromatography, which is provided by Chinese Pharmacopoeia. The statistical F test, Student's t test, and nonparametric test at 95% confidence level indicate that there was no significant difference between these two methods. qNMR is a simple and accurate quantitative tool with no need for specific corresponding reference standards. It has the potential of the quantitative analysis of other peptide drugs and standardization of the corresponding reference standards.


Assuntos
Octreotida/química , Calibragem , Óxido de Deutério/química , Espectroscopia de Prótons por Ressonância Magnética/normas , Padrões de Referência
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