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1.
J Chromatogr A ; 1635: 461720, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33234293

RESUMO

The LFER model of Abraham is applied to the retention of the neutral and ionic forms of 94 solutes in a C18 column and 40% v/v acetonitrile/water mobile phase. The results show that polarizability and cavity formation interactions increase retention, whereas dipole and hydrogen bonding interactions favours partition to the mobile phase and thus, they decrease retention. The coefficients of the ionic descriptors measure the effect of the electrostatic interactions and their contribution to partition of the cation or anion between the two mobile and stationary chromatographic phases. A new LFER model for application to the retention of partially dissociated acids and bases is derived averaging the descriptors of the neutral and ionic forms according to their degrees of ionization in the mobile phase. This new LFER model is satisfactorily compared to other literature modified Abraham models for a set of 498 retention data of partially dissociated acids and bases. All tested models require the calculation of the ionization degrees of the compounds at the measuring pH. Calculation of the ionization degrees in the chromatographic mobile phase (i.e. from pH and pKa in the eluent) give good correlations for all tested models. However, estimation of these ionization degrees from pH - pKa data in pure water gives biased estimations of the retention of the partially ionized solutes.


Assuntos
Cromatografia de Fase Reversa , Modelos Químicos , Acetonitrilos/química , Ácidos/química , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Íons/química , Soluções , Água/química
2.
J Chromatogr A ; 1635: 461701, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33254003

RESUMO

The paper presents the first application of deep eutectic solvents (DES) as stationary phases for gas chromatography. DES obtained by mixing tetrabutylammonium chloride (TBAC) as a hydrogen bond acceptor (HBA) with heptadecanoic acid being a hydrogen bond donor (HBD) in a mole ratio of HBA:HBD equal to 1:2 was characterized by its ability to separate volatile organic compounds (VOCs). The Rohrschneider - McReynolds constants determined reveal that the synthesized DES is a stationary phase of medium polarity. A detailed retention characteristic was determined for a number of groups of chemical compounds, including aromatic hydrocarbons, alcohols, ketones, sulfides and thiophene derivatives. The synthesized DES was found to have a high selectivity towards alcohols. At the same time, the investigated stationary phase was found to have specific interactions with some analytes. For example, a stronger retention was observed for 1-hexanol and 1-heptanol compared to other alcohols. Retention times of these two alcohols are longer by 191% and 300%, respectively, relative to the expected value based on their boiling point. Such an increased retention is caused by a synergistic effect of various kinds of interactions - the possibility of formation of hydrogen bonds between the DES and the hydroxyl group of alcohols and hydrophobic interactions of alkyl chains of the DES with the alkyl chain of alcohols. The ability to modify properties of DESs by replacement of HBA or HBD with a different chemical compound or by dissolving in DES macromolecular substances makes the proposed stationary phase highly flexible. In addition to using the developed DES in chromatographic techniques, the retention data collected indicate the possibility of its application to other separation techniques, i.e. extractive distillation.


Assuntos
Cromatografia Gasosa/métodos , Solventes/química , Álcoois/química , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Compostos de Amônio Quaternário/química , Temperatura de Transição
3.
Food Chem ; 340: 127893, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32889202

RESUMO

In this work, zein/carboxymethyl dextrin nanoparticles were successfully fabricated at different zein to carboxymethyl dextrin (CMD) mass ratios. Zein/CMD nanoparticles with the negative charge and the smallest size (212 nm) were formed when the mass ratio of zein to CMD was 2:1, exhibiting improved encapsulation efficiency of curcumin (85.5%). Electrostatic interactions, hydrogen bonding and hydrophobic interactions were main driven forces for nanoparticles formulation and curcumin encapsulation. Fourier transform infrared spectroscopy determined curcumin might be partially embedded in CMD during encapsulation. The spherical structures of zein/CMD nanoparticles and curcumin-loaded zein/CMD nanoparticles were observed by transmission electron microscopy. The photothermal stability and antioxidant activity of curcumin were significantly enhanced after be loaded in zein/CMD nanoparticles. Furthermore, encapsulation of curcumin in zein/CMD nanoparticles significantly delayed the release of curcumin in simulated gastrointestinal fluids. These results indicated that zein/CMD nanoparticles could be effective encapsulating materials for bioactive compounds in food industry.


Assuntos
Antioxidantes/química , Curcumina/farmacocinética , Dextrinas/química , Nanopartículas/química , Zeína/química , Antioxidantes/farmacologia , Curcumina/administração & dosagem , Curcumina/química , Preparações de Ação Retardada , Estabilidade de Medicamentos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Transmissão , Nanopartículas/administração & dosagem , Tamanho da Partícula , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Difração de Raios X
4.
J Biosci Bioeng ; 131(1): 8-12, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33023861

RESUMO

Sphingomyelinase C (SMC) hydrolyzes sphingomyelin to ceramide and phosphocholine. Prokaryotic SMCs share sequence homology with mammalian SMCs that have enzymatic pH optima at neutral pH. SMC from the nonpathogenic prokaryote Streptomyces griseocarneus shows notable enzymatic features such as higher optimum pH and thermostability than other prokaryotic SMCs. Determination of the three-dimensional structure of S. griseocarneus-SMC (Sg-SMC) and comparison with other SMC structures represents a promising strategy to elucidate the unique enzymatic features of Sg-SMC on a structural basis. Therefore, we determined the crystal structure of Sg-SMC at 2.0 Å resolution by X-ray crystallography. Comparison of the Sg-SMC structure with three other structurally known SMCs from Listeria ivanovii, Bacillus cereus, and Staphylococcus aureus indicated that Sg-SMC is more diverse in sequence and that structural differences in the main chain between these SMCs are primarily located on the molecular surface distant from the active site. Comparison of the surface area of the four SMCs revealed that Sg-SMC has the most compact structure, which may contribute to the enhanced thermostability of Sg-SMC. Regarding the hydrogen bond network in the active site of Sg-SMC, a basic amino acid, Arg278, is involved, whereas the corresponding residue in other SMCs (Ser or Asn) does not form hydrogen bonds with metal-coordinating water molecules. Hydrogen bond formation between Arg278 and a Mg2+ ion-coordinating water molecule may be responsible for the higher optimal pH of Sg-SMC compared to that of other SMCs.


Assuntos
Esfingomielina Fosfodiesterase/química , Esfingomielina Fosfodiesterase/metabolismo , Streptomyces/enzimologia , Temperatura , Animais , Domínio Catalítico , Cristalografia por Raios X , Estabilidade Enzimática , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio
5.
Food Chem ; 340: 128160, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33011469

RESUMO

Quantitative analyses of chemical components and sensory tests were carried out on vodka samples to test for stimulative taste of ethanol. Proton nuclear magnetic resonance (1H NMR) spectra of the vodkas were measured with 600 MHz NMR. The effects of salts on the alcohol-stimulative taste were investigated for 15% (v/v) EtOH-H2O solution. 1H NMR spectroscopy results showed that a magnesium salt could reduce the stimulative taste of ethanol organoleptically and, at the same time, strengthen the hydrogen-bonding structure of water-ethanol, although the effect of the magnesium could not be clarified quantitatively in the products of vodka. It was also suggested that a change in the water-ethanol hydrogen-bonding structure could lead to a reduction in the stimulative taste of ethanol in vodka.


Assuntos
Bebidas Alcoólicas/análise , Paladar , Etanol/química , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Soluções , Água/química
6.
Food Chem ; 340: 128198, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33032147

RESUMO

In this study, potential of dielectric-barrier discharge (DBD) plasma treatment (40 kV, 12 kHz at 1, 2, 3 and 4 min) to eliminate soybean agglutinin (SBA) activity was investigated in a SBA model system and soymilk. The plasma treatment decreased the SBA in the model system and hemagglutination activity was decreased by 87.31%. SDS-PAGE analysis confirmed the degradation of the SBA polypeptide chain. The multi-spectroscopic analysis revealed a two-stage structure alteration in the SBA upon exposure to the plasma treatment. Oxidation of NH-/NH2- at the peptide bond disrupted the hydrogen bonds and altered the secondary structure of SBA. Further oxidation of aromatic amino acid, cleavage of peptide bonds and the breakage of polypeptide led to the SBA fragmentation and complete unfolding of the protein. The SBA inactivation by the plasma treatment was confirmed in soymilk. Plasma treatment is a promising technology for the elimination of SBA in soybean product.


Assuntos
Lectinas de Plantas/química , Gases em Plasma/química , Proteínas de Soja/química , Impedância Elétrica , Ligação de Hidrogênio , Oxirredução , Estrutura Secundária de Proteína , Leite de Soja/química
7.
J Environ Sci (China) ; 100: 328-339, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33279046

RESUMO

Amides, a series of significant atmospheric nitrogen-containing volatile organic compounds (VOCs), can participate in new particle formation (NPF) throught interacting with sulfuric acid (SA) and organic acids. In this study, we investigated the molecular interactions of formamide (FA), acetamide (AA), N-methylformamide (MF), propanamide (PA), N-methylacetamide (MA), and N,N-dimethylformamide (DMF) with SA, acetic acid (HAC), propanoic acid (PAC), oxalic acid (OA), and malonic acid (MOA). Global minimum of clusters were obtained through the association of the artificial bee colony (ABC) algorithm and density functional theory (DFT) calculations. The conformational analysis, thermochemical analysis, frequency analysis, and topological analysis were conducted to determine the interactions of hydrogen-bonded molecular clusters. The heterodimers formed a hepta or octa membered ring through four different types of hydrogen bonds, and the strength of the bonds are ranked in the following order: SOH•••O > COH•••O > NH•••O > CH•••O. We also evaluated the stability of the clusters and found that the stabilization effect of amides with SA is weaker than that of amines with SA but stronger than that of ammonia (NH3) with SA in the dimer formation of nucleation process. Additionally, the nucleation capacity of SA with amides is greater than that of organic acids with amides.


Assuntos
Amidas , Hidrogênio , Ligação de Hidrogênio , Modelos Teóricos , Ácidos Sulfúricos
8.
Food Chem ; 337: 127996, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32919275

RESUMO

Hydroxytyrosol oligomer prepared by bioenzyme shows stronger health-promoting properties than its monomer. However, the polymerization process carried out by laccase, tyrosinase or horseradish peroxidase is still lacking in term of product characterization, kinetics and thermodynamics. To achieve these aspects, ATR-FT-IR, NMR, the Michaelis-Menten equation and isothermal titration calorimetry were explored. The results showed that the identified polymers presented a CC bond and a degree of polymerization less than six. Laccase showed the greatest affinity to hydroxytyrosol via comparison of Km and Vm. All of these polymerization processes were spontaneous and exothermic behaviuors ranging from 30 to 50 °C, and were driven by hydrogen bonds, van der Waals interactions and hydrophobic interactions. Furthermore, circular dichroism spectroscopy was used to reveal the enzymatic structural changes during the catalysis, which showed that ß-sheet levels for laccase, α-helix levels for tyrosinase, and the α-helix and random coil levels for horseradish peroxidase were dramatically decreased.


Assuntos
Catecol Oxidase/metabolismo , Peroxidase do Rábano Silvestre/metabolismo , Polimerização , Calorimetria/métodos , Catálise , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Lacase/metabolismo , Oxirredução , Álcool Feniletílico/análogos & derivados , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
9.
Food Chem ; 337: 128019, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32927227

RESUMO

In this study, the nanocomplexes as a novel delivery system for curcumin, were successfully fabricated using high methoxyl pectin (HMP), individual surfactants (rhamnolipid (Rha), tea saponin (TS) and ethyl lauroyl arginate hydrochloride (ELA)) and pea protein isolate (PPI). The optimum mass ratio between PPI and curcumin was 40:1. The HMP-Rha-PPI-Cur, HMP-TS-PPI-Cur and HMP-ELA-PPI-Cur complexes which had particle sizes of 453, 422 and 587 nm, exhibited encapsulation efficiencies of curcumin with 93.46, 92.05 and 86.73%, respectively. The analysis of FTIR revealed that HMP-surfactant-PPI-Cur complexes were formed mainly by hydrogen bonding and electrostatic attraction. XRD result showed that curcumin exhibited a non-crystallized state in the ternary complexes. Moreover, the curcumin within the HMP-Rha-PPI ternary complexes showed better stability under UV-light, thermal and simulated gastrointestinal conditions.


Assuntos
Curcumina/administração & dosagem , Proteínas de Ervilha/química , Polissacarídeos/química , Tensoativos/química , Curcumina/química , Glicolipídeos , Ligação de Hidrogênio , Modelos Biológicos , Nanopartículas/química , Tamanho da Partícula , Pectinas/química
10.
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
11.
Food Chem ; 339: 127939, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152852

RESUMO

In this work, high-resolution mass spectrometry was used to identify the oxidation sites and forms of ß-lactoglobulin (ß-Lg) induced by hydrogen peroxide with 1.5% concentration, and the influence of oxidation sites on the structure of ß-Lg was discussed from the molecular level. Twelve kinds of oxidation products and 36 oxidation sites were identified, including sulfoxidation in sulfur-containing amino acid residue, hydroxylation in aromatic group residue, deamination in amino-containing amino acid etc. The destruction of hydrogen bonds and disulfide bonds in ß-Lg caused by oxidation is the main factor causing its structural changes, which were manifested in the decrease of ß-sheet component and increase of ß-turns and random coil contents, intrinsic fluorescence intensity and surface hydrophobicity. In addition, several peptides as potential oxidative markers were found to be capable of monitoring the degree of oxidation of ß-Lg. In short, this work provided insights into structural changes of ß-Lg by oxidation.


Assuntos
Lactoglobulinas/química , Espectrometria de Massas , Animais , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Oxirredução
12.
Food Chem ; 339: 128145, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152895

RESUMO

The solution turbidity and intrinsic fluorescence quenching increased after procyanidin was mixed with lactoferrin. The addition of procyanidin also caused a reduction in the surface hydrophobicity of the lactoferrin, suggesting procyanidin bound to non-polar patches on lactoferrin's surfaces. Moreover, the binding interaction caused an appreciable alteration in the structure of both the polyphenol and protein. Thermodynamic analysis indicated the interaction was spontaneous and mainly driven by entropy changes, suggesting that hydrophobic interactions dominated. A computational docking simulation provided insights into the location of the most-likely binding sites on the protein, as well as the nature of the interaction forces involved. In particular, both hydrophobic and hydrogen bonding were found to be important. The binding of the procyanidin to the lactoferrin enhanced its foaming properties. These results may lead to the development of a new class of natural functional ingredients that can be used in food products to improve their quality attributes.


Assuntos
Biflavonoides/química , Catequina/química , Lactoferrina/química , Proantocianidinas/química , Animais , Biflavonoides/metabolismo , Sítios de Ligação , Catequina/metabolismo , Bovinos , Fluorescência , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Lactoferrina/metabolismo , Simulação de Acoplamento Molecular , Proantocianidinas/metabolismo , Espectrometria de Fluorescência , Termodinâmica
13.
Chemosphere ; 263: 127892, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32822943

RESUMO

Nitrogen-doped porous graphene oxide (N-PGO) was synthesized, characterized, and applied as a hydrophilic nanomaterial in fabrication of polyethersulfone (PES) membrane for Reactive Red 195 dye and bovine serum albumin (BSA) protein separation. The N-PGO nanosheets not merely showed a good adhesion towards polymers, but simultaneously promoted hydrogen bonding action. Therefore, high-efficiency permeation passageway in the separation layer of membranes was attained. X-ray photoelectron spectroscopy (XPS), energy dispersive spectroscopy (EDX) and Fourier transform infra-red spectroscopy (FTIR) analyses approved nitrogen doping, which increased hydrophilicity and hydrogen bonding ability of PGO in water filtration. The pure water permeation of nanocomposite membranes could reach as high as 190 L m-2 h-1 at 3 bar. A dye rejection efficiency higher than 92% and BSA rejection higher than 95% were accordingly obtained. Atomic force microscopy (AFM) images approved formation of a rough surface that was decreased by addition of low amounts of the PGO. SEM images provided from the surface also confirmed enlarged pore size and increased porosity. Antifouling properties were investigated by BSA filtration, and results showed that the flux recovery ratio of the N-PGO membrane was improved. Overall, the N-PGO hybrid membranes exhibited potential for application in separation of typical proteins and dyes with good antifouling properties.


Assuntos
Corantes/química , Nanocompostos/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Animais , Bovinos , Corantes/análise , Filtração , Grafite/química , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Membranas Artificiais , Nitrogênio , Polímeros/química , Porosidade , Soroalbumina Bovina/química , Sulfonas , Água/química , Poluentes Químicos da Água/análise
14.
Food Chem ; 340: 127915, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32889208

RESUMO

The interaction between cyanidin-3-O-glucoside with casein and casein hydrolysates and its effects on the antioxidant activity of complexes were investigated. Fluorescence spectroscopy results indicated that the interaction between cyanidin-3-O-glucoside and casein was primarily mediated by Van der Waals forces or hydrogen bonds and stronger than the interaction between cyanidin-3-O-glucoside and casein hydrolysates mainly via hydrophobic interaction. Circular dichroism and Fourier-transform infrared spectroscopy analysis showed the secondary structure of casein/casein hydrolysates had a slight change after binding with cyanidin-3-O-glucoside. And larger particles formed due to the protein aggregation induced by the complexation of casein/casein hydrolysates with cyanidin-3-O-glucoside. The antioxidant activity assessments revealed that the synergistic effect was observed in FRAP assay, whereas an antagonistic effect in ABTS assay between casein/casein hydrolysates and cyanidin-3-O-glucoside, which were produced due to the casein/casein hydrolysates-cyanidin-3-O-glucoside interaction. These results would be helpful in designing functional beverages containing anthocyanins and protein hydrolysates with enhanced antioxidant ability.


Assuntos
Antocianinas/química , Antioxidantes/química , Caseínas/química , Glucosídeos/química , Antocianinas/metabolismo , Antioxidantes/metabolismo , Caseínas/metabolismo , Dicroísmo Circular , Glucosídeos/metabolismo , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Estrutura Secundária de Proteína , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Food Chem ; 334: 127585, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32711275

RESUMO

Glycerol monosterate (GMS) and stearic acid (SA) share a similar carbon chain structure while SA has a carboxyl head group and GMS has two free hydroxyl groups. The current research focuses on the relationship between GMS and SA chemical structure, nano and mesoscale crystal structure, and the oleogel macroscopic characteristics. Molecular analysis revealed the formation of different types of hydrogen bonds, which disappear upon temperature increase at different temperatures. Nano-structural analysis exhibited tight and ordered lamellar structures for SA compared with loosely packed short lamellar structures in GMS oleogel, presumably due to its larger hydrophilic head group. Microstructure imaging revealed ordered anisotropically orientated needle-like crystals in SA and isotopically ordered braid-like crystals in GMS oleogels. Mechanical analysis revealed that gel strength is enhanced when crystal structure is isotropically oriented, similar behavior seen is composite materials, where the structuring agent crystals behave like a reinforcing agent within the oil matrix.


Assuntos
Ácidos Esteáricos/química , Ligação de Hidrogênio , Nanoestruturas/química , Compostos Orgânicos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Termogravimetria , Difração de Raios X
16.
Environ Pollut ; 268(Pt B): 115798, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33126159

RESUMO

The binding of PAHs with DNA to form PAH-DNA adducts is a crucial step in PAH-induced carcinogenesis. How functional groups affect this binding is largely unknown. Here, we observed that functional group substitutions strongly inhibited PAH-DNA binding. Additionally, -OH substitution has the most potent inhibitory effect as it causes the smallest change in the electrostatic surface potential. Fourier transform infrared spectroscopy and molecular docking analyses demonstrated that PAH derivatives bind with guanine via intercalation and groove binding and then non-specifically insert into the major/minor grooves of DNA. Quantum chemical calculations suggested that hydrogen/halogen bonding may be essential in affecting the binding of functional group-substituted PAHs with DNA. It was further revealed that Log KOA and the PAH derivatives' melting points correlated significantly with binding affinity, implying that changes in the physicochemical characteristics are important factors. This study opens a new window for understanding the relationship between highly toxic PAH derivatives and genetic materials.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , DNA , Adutos de DNA , Ligação de Hidrogênio , Radical Hidroxila , Simulação de Acoplamento Molecular
17.
J Immunol Res ; 2020: 8893483, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33274246

RESUMO

The global health crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19, has resulted in a negative impact on human health and on social and economic activities worldwide. Researchers around the globe need to design and develop successful therapeutics as well as vaccines against the novel COVID-19 disease. In the present study, we conducted comprehensive computer-assisted analysis on the spike glycoprotein of SARS-CoV-2 in order to design a safe and potent multiepitope vaccine. In silico epitope prioritization shortlisted six HLA I epitopes and six B-cell-derived HLA II epitopes. These high-ranked epitopes were all connected to each other via flexible GPGPG linkers, and at the N-terminus side, the sequence of Cholera Toxin ß subunit was attached via an EAAAK linker. Structural modeling of the vaccine was performed, and molecular docking analysis strongly suggested a positive association of a multiepitope vaccine with Toll-like Receptor 3. The structural investigations of the vaccine-TLR3 complex revealed the formation of fifteen interchain hydrogen bonds, thus validating its integrity and stability. Moreover, it was found that this interaction was thermodynamically feasible. In conclusion, our data supports the proposition that a multiepitope vaccine will provide protective immunity against COVID-19. However, further in vivo and in vitro experiments are needed to validate the immunogenicity and safety of the candidate vaccine.


Assuntos
/imunologia , Epitopos de Linfócito T/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Sequência de Aminoácidos , /prevenção & controle , Biologia Computacional , Simulação por Computador , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/química , Humanos , Ligação de Hidrogênio , Imunogenicidade da Vacina , Simulação de Acoplamento Molecular , Pandemias/prevenção & controle , Glicoproteína da Espícula de Coronavírus/química , Eletricidade Estática , Termodinâmica , Vacinas de Subunidades/imunologia
18.
J Phys Chem B ; 124(50): 11337-11348, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33264025

RESUMO

The outbreak of a new coronavirus SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) has caused a global COVID-19 (coronavirus disease 2019) pandemic, resulting in millions of infections and thousands of deaths around the world. There is currently no drug or vaccine for COVID-19, but it has been revealed that some commercially available drugs are promising, at least for treating symptoms. Among them, remdesivir, which can block the activity of RNA-dependent RNA polymerase (RdRp) in old SARS-CoV and MERS-CoV viruses, has been prescribed to COVID-19 patients in many countries. A recent experiment showed that remdesivir binds to SARS-CoV-2 with an inhibition constant of µM, but the exact target has not been reported. In this work, combining molecular docking, steered molecular dynamics, and umbrella sampling, we examined its binding affinity to two targets including the main protease (Mpro), also known as 3C-like protease, and RdRp. We showed that remdesivir binds to Mpro slightly weaker than to RdRp, and the corresponding inhibition constants, consistent with the experiment, fall to the µM range. The binding mechanisms of remdesivir to two targets differ in that the electrostatic interaction is the main force in stabilizing the RdRp-remdesivir complex, while the van der Waals interaction dominates in the Mpro-remdesivir case. Our result indicates that remdesivir can target not only RdRp but also Mpro, which can be invoked to explain why this drug is effective in treating COVID-19. We have identified residues of the target protein that make the most important contribution to binding affinity, and this information is useful for drug development for this disease.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/metabolismo , /metabolismo , /metabolismo , Monofosfato de Adenosina/metabolismo , Alanina/metabolismo , Algoritmos , Humanos , Ligação de Hidrogênio , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , /enzimologia , Eletricidade Estática
19.
J Phys Chem Lett ; 11(24): 10446-10453, 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33269932

RESUMO

The SARS-CoV-2 pandemic has already killed more than one million people worldwide. To gain entry, the virus uses its Spike protein to bind to host hACE-2 receptors on the host cell surface and mediate fusion between viral and cell membranes. As initial steps leading to virus entry involve significant changes in protein conformation as well as in the electrostatic environment in the vicinity of the Spike/hACE-2 complex, we explored the sensitivity of the interaction to changes in ionic strength through computational simulations and surface plasmon resonance. We identified two regions in the receptor-binding domain (RBD), E1 and E2, which interact differently with hACE-2. At high salt concentration, E2-mediated interactions are weakened but are compensated by strengthening E1-mediated hydrophobic interactions. These results provide a detailed molecular understanding of Spike RBD/hACE-2 complex formation and stability under a wide range of ionic strengths.


Assuntos
/química , Glicoproteína da Espícula de Coronavírus/química , Sequência de Aminoácidos , Sítios de Ligação , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Concentração Osmolar , Ligação Proteica , Conformação Proteica , Domínios Proteicos
20.
BMC Bioinformatics ; 21(Suppl 17): 557, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33308148

RESUMO

BACKGROUND: The immune checkpoint receptor programmed cell death protein I (PD-1) has been identified as a key target in immunotherapy. PD-1 reduces the risk of autoimmunity by inducing apoptosis in antigen-specific T cells upon interaction with programmed cell death protein ligand I (PD-L1). Various cancer types overexpress PD-L1 to evade the immune system by inducing apoptosis in tumor-specific CD8+ T cells. The clinically used blocking antibody nivolumab binds to PD-1 and inhibits the immunosuppressive interaction with PD-L1. Even though PD-1 is already used as a drug target, the exact mechanism of the receptor is still a matter of debate. For instance, it is hypothesized that the signal transduction is based on an active conformation of PD-1. RESULTS: Here we present the results of the first molecular dynamics simulations of PD-1 with a complete extracellular domain with a focus on the role of the BC-loop of PD-1 upon binding PD-L1 or nivolumab. We could demonstrate that the BC-loop can form three conformations. Nivolumab binds to the BC-loop according to the conformational selection model whereas PD-L1 induces allosterically a conformational change of the BC-loop. CONCLUSION: Due to the structural differences of the BC-loop, a signal transduction based on active conformation cannot be ruled out. These findings will have an impact on drug design and will help to refine immunotherapy blocking antibodies.


Assuntos
Antígeno B7-H1/química , Simulação de Dinâmica Molecular , Nivolumabe/imunologia , Receptor de Morte Celular Programada 1/química , Anticorpos Monoclonais/imunologia , Antígeno B7-H1/metabolismo , Análise por Conglomerados , Humanos , Ligação de Hidrogênio , Ligantes , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Ligação Proteica , Domínios Proteicos
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