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1.
Chemosphere ; 282: 131128, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34470167

RESUMO

We introduce a novel, efficient and fast method for the total and simultaneous removal of monomethylmercury, dimethylmercury, ethylmercury and Hg (II) from aquatic environments using magnetic core nanoparticles, coated with metallic nanomeric silver and functionalized with l-Cysteine. As far as the authors know, simultaneous removal has not been achieved previously. The experimental design was based on exploring a wide range of experimental conditions, including pH of the medium (2-12), contact time (up to 20 min), adsorbent dose (50-800 µL) and temperature (293-323 K), in order to achieve the highest adsorption efficiency. The results show that, for a pH equal to 6.2 at room temperature, 400 µL of nanoparticles is sufficient to achieve 100% adsorption efficiency for all the studied Hg species after a contact time of 30 s. The adsorbent was characterized by means of Scanning Electron Microscopy, Energy Dispersive X-ray Analysis, Fourier-Transform Infrared Spectroscopy and a BET test. Moreover, the procedure allows the total recovery and recycling of the nanoparticles using 50 µL of 0.01 M KI. As regards reuse, the adsorbent exhibits no loss of adsorption capacity during the first three adsorption cycles. Thermodynamics reveals that adsorption is of a physicochemical nature, the equilibrium isotherms being described by a Langmuir model for all the Hg species. The ability of the method to simultaneously adsorb all species of mercury present in water, achieving full adsorption in just a few seconds, along with the simple experimental conditions and its cost-effectiveness, strongly support the approach as an alternative to current procedures.


Assuntos
Nanopartículas de Magnetita , Mercúrio , Poluentes Químicos da Água , Adsorção , Cisteína , Concentração de Íons de Hidrogênio , Cinética , Projetos de Pesquisa , Prata , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Poluentes Químicos da Água/análise
2.
Int J Mol Sci ; 22(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502041

RESUMO

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak in December 2019 has caused a global pandemic. The rapid mutation rate in the virus has created alarming situations worldwide and is being attributed to the false negativity in RT-PCR tests. It has also increased the chances of reinfection and immune escape. Recently various lineages namely, B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.617.3 have caused rapid infection around the globe. To understand the biophysical perspective, we have performed molecular dynamic simulations of four different spikes (receptor binding domain)-hACE2 complexes, namely wildtype (WT), Alpha variant (N501Y spike mutant), Kappa (L452R, E484Q) and Delta (L452R, T478K), and compared their dynamics, binding energy and molecular interactions. Our results show that mutation has caused significant increase in the binding energy between the spike and hACE2 in Alpha and Kappa variants. In the case of Kappa and Delta variants, the mutations at L452R, T478K and E484Q increased the stability and intra-chain interactions in the spike protein, which may change the interaction ability of neutralizing antibodies to these spike variants. Further, we found that the Alpha variant had increased hydrogen interaction with Lys353 of hACE2 and more binding affinity in comparison to WT. The current study provides the biophysical basis for understanding the molecular mechanism and rationale behind the increase in the transmissivity and infectivity of the mutants compared to wild-type SARS-CoV-2.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/transmissão , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/metabolismo , Enzima de Conversão de Angiotensina 2/ultraestrutura , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/metabolismo , COVID-19/virologia , Cristalografia por Raios X , Humanos , Simulação de Dinâmica Molecular , Mutação , Estabilidade Proteica , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/ultraestrutura , Termodinâmica
3.
Water Sci Technol ; 84(3): 552-575, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34388119

RESUMO

In this study, a response surface methodology (RSM) approach using central composite design (CCD) was investigated to develop a mathematical model and to optimize the effects of pH, adsorbent amount and temperature related to the hexavalent chromium removal by biosorption on peanut shells (PSh). The highest removal percentage of 30.28% was found by the predicted model under the optimum conditions (pH of 2.11, 0.73 g of PSh and 37.2 °C) for a 100 mg/L initial Cr(VI) concentration, which was very near to the experimental value (29.92%). The PSh was characterized by SEM, EDX, FTIR, BET, XRD analyses. Moreover, a Langmuir isotherm fitted well (R2 = 0.992) with the experimental data, and the maximum adsorption capacity was discovered to be 2.48 and 3.49 mg/g respectively at 25 and 45 °C. Kinetic data were well foreseen by pseudo second order. Thermodynamic study depicted that biosorption of Cr(VI) onto PSh was spontaneous and endothermic. Regeneration of the PSh using NaOH showed a loss <5% in the Cr(VI) removal efficiency up to three recycle runs. In summary, the Cr(VI) removal onto economic, sensitive and selective biosorbent (PSh) was optimized using CCD to study biosorption behaviors.


Assuntos
Poluentes Químicos da Água , Adsorção , Biomassa , Cromo/análise , Concentração de Íons de Hidrogênio , Cinética , Termodinâmica , Poluentes Químicos da Água/análise
4.
Water Sci Technol ; 84(3): 609-631, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34388122

RESUMO

Serious environmental deterioration caused by synthetic waste plastics, and the pollution of freshwater resources are the most alarming and marked challenges of the 21st century. Therefore, immense scientific efforts are being made towards the management of waste plastics and treatment of polluted water. The current study reports on the utilization of waste polyethylene terephthalate (wPET) and waste polystyrene (wPS) for fabrication of activated carbon (AC) and its application for the removal of hazardous polycyclic aromatic hydrocarbons (PAHs) pollutants from water. AC was prepared from wPET and wPS by carbonization under a N2 atmosphere followed by chemical activation with 1 M KOH and 1 M HCl. The AC was characterized by scanning electron microscopy, surface area analysis, and Fourier transform infrared spectroscopy. Adsorption of PAHs from aqueous solutions through AC was examined by batch adsorption tests. The optimum parameters for maximum adsorption of PAHs were found to be: initial PAHs concentration 40 ppm, 2 h contact time, pH 3, 5, and 7, 50 °C temperature and adsorbent dose of 0.8 g. Kinetic and isotherm models were applied to evaluate the adsorbent capacity for PAHs adsorption. The kinetic study shows that the adsorption of these PAHs onto AC follows pseudo-second-order kinetics. The experimental results demonstrated that the Langmuir isotherm model best fitted the data. The thermodynamic factors calculated such as entropy change (ΔS°), enthalpy change (ΔS°) and free energy change (ΔG°) show that the adsorption process is non-spontaneous and endothermic in nature. Results were also compared with the efficiencies of some commercial adsorbents used in practice. This examination revealed that the novel plastic-derived AC possesses a great potential for elimination and recovery of PAH elimination from industrial wastewater.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Adsorção , Carvão Vegetal , Descontaminação , Concentração de Íons de Hidrogênio , Cinética , Plásticos , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Águas Residuárias , Poluentes Químicos da Água/análise
5.
Water Sci Technol ; 84(3): 697-711, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34388128

RESUMO

Carboxylic acids are the main pollutant of industrial wastewater during the advanced oxidation process (AOPs). In this study, a resin-based spherical activated carbon (RSAC, AF5) as an adsorbent was examined and acetic acid was used as a model substrate for adsorption investigation. The pH = 3, temperature = 298 K were fixed by batch technique. The pseudo-second-order kinetic model, the intraparticle and external models are fitted well, and it was found that the adsorption of acetic acid onto AF5 was controlled by liquid film diffusion. A Freundlich model indicated that the adsorption process was heterogeneous multimolecular layer adsorption on the surface. AF5 shows good regenerative ability; the recovery rate of adsorption capacity was ∼88% after five cycles. Chemical oxygen demand (COD) adsorption removal rate could be maintained at 100% for over 35 h in an actual AOPs effluent, and could be eluted for 100% after 8 h by 0.8wt% NaOH. Characterizations, including XRF, XRD, TG/DSC,FTIR, SEM and N2 adsorption, showed that the excellent adsorption performance was mainly due to the microporous structure and large specific surface area (1,512.88 m2/g), the adsorption mechanism mainly included pore filling effect and electrostatic attraction. After five adsorption recycles, AF5's pore characteristic did not change significantly. This study provides a scientific basis for the wastewater standard discharge process of AOPs coupled adsorption.


Assuntos
Carvão Vegetal , Poluentes Químicos da Água , Ácido Acético , Adsorção , Difusão , Concentração de Íons de Hidrogênio , Cinética , Termodinâmica
6.
J Chem Phys ; 155(4): 045101, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34340389

RESUMO

Understanding the permeation of biomolecules through cellular membranes is critical for many biotechnological applications, including targeted drug delivery, pathogen detection, and the development of new antibiotics. To this end, computer simulations are routinely used to probe the underlying mechanisms of membrane permeation. Despite great progress and continued development, permeation simulations of realistic systems (e.g., more complex drug molecules or biologics through heterogeneous membranes) remain extremely challenging if not intractable. In this work, we combine molecular dynamics simulations with transition-tempered metadynamics and techniques from the variational approach to conformational dynamics to study the permeation mechanism of a drug molecule, trimethoprim, through a multicomponent membrane. We show that collective variables (CVs) obtained from an unsupervised machine learning algorithm called time-structure based Independent Component Analysis (tICA) improve performance and substantially accelerate convergence of permeation potential of mean force (PMF) calculations. The addition of cholesterol to the lipid bilayer is shown to increase both the width and height of the free energy barrier due to a condensing effect (lower area per lipid) and increase bilayer thickness. Additionally, the tICA CVs reveal a subtle effect of cholesterol increasing the resistance to permeation in the lipid head group region, which is not observed when canonical CVs are used. We conclude that the use of tICA CVs can enable more efficient PMF calculations with additional insight into the permeation mechanism.


Assuntos
Farmacocinética , Aprendizado de Máquina não Supervisionado , Algoritmos , Colesterol/química , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Fosfatidilcolinas/química , Termodinâmica , Trimetoprima/química
7.
Artigo em Inglês | MEDLINE | ID: mdl-34347579

RESUMO

Combustion of High-sulfur oil sludge (OS) blended with CaO can significantly reduce the emission of sulfur gas pollutants, but its combustion and kinetic characteristics need to be further studied. TGA experiments showed the combustion characteristics of OS were significantly changed after adding CaO. As reflected by comprehensive combustion index (S), the combustion performance of OS decreased after adding CaO, and significantly improved with the increase of heating rate. The kinetic parameters of the main combustion process of OS with CaO were calculated by the iso-conversion methods of Friedman, FWO, and Starink, respectively. Kinetic analysis results indicated the energy required for OS combustion with CaO first increased and then decreased with deepening of reaction degree. The thermodynamic parameters of ΔH, ΔG and ΔS were determined on the basis of kinetics. The negative ΔH, positive ΔG, and negative ΔS validated the combustion of OS with CaO was an exothermic and nonspontaneous process.


Assuntos
Calefação , Esgotos , Cinética , Termodinâmica , Termogravimetria
8.
Molecules ; 26(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34443360

RESUMO

Plasma proteins play a fundamental role in living organisms. They participate in the transport of endogenous and exogenous substances, especially drugs. 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium salts, have been synthesized as potential anticancer substances used for cancer treatment. Most anticancer substances generate a toxic effect on the human body. In order to check the toxicity and therapeutic dosage of these chemicals, the study of ligand binding to plasma proteins is very relevant. The present work presents the first comparative analysis of the binding of one of the 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium derivatives (Salt1) with human serum albumin (HSA), α-1-acid glycoprotein (AGP) and human gamma globulin (HGG), assessed using fluorescence, UV-Vis and CD spectroscopy. In order to mimic in vivo ligand-protein binding, control normal serum (CNS) was used. Based on the obtained data, the Salt1 binding sites in the tertiary structure of all plasma proteins and control normal serum were identified. Both the association constants (Ka) and the number of binding site classes (n) were calculated using the Klotz method. The strongest complex formed was Salt1-AGPcomplex (Ka = 7.35·104 and 7.86·104 mol·L-1 at excitation wavelengths λex of 275 and 295 nm, respectively). Lower values were obtained for Salt1-HSAcomplex (Ka = 2.45·104 and 2.71·104 mol·L-1) and Salt1-HGGcomplex (Ka = 1.41·104 and 1.33·104 mol·L-1) at excitation wavelengths λex of 275 and 295 nm, respectively, which is a positive phenomenon and contributes to the prolonged action of the drug. Salt1 probably binds to the HSA molecule in Sudlow sites I and II; for the remaining plasma proteins studied, only one binding site was observed. Moreover, using circular dichroism (CD), fluorescence and UV-Vis spectroscopy, no effect on the secondary and tertiary structures of proteins in the absence or presence of Salt1 has been demonstrated. Despite the fact that the conducted studies are basic, from the scientific point of view they are novel and encourage further in vitro and in vivo investigations. As a next part of the study (Part 2), the second new synthetized quinobenzothiazine derivative (Salt2) will be analyzed and published.


Assuntos
Proteínas Sanguíneas/metabolismo , Análise Espectral , Tiazinas/química , Tiazinas/metabolismo , Proteínas Sanguíneas/química , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica , Termodinâmica
9.
J Phys Chem Lett ; 12(32): 7659-7664, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34351767

RESUMO

From stem cell freeze-drying to organ storage, considerable recent efforts have been directed toward the development of new preservation technologies. A prominent protein stabilizing strategy involves vitrification in glassy matrices, most notably those formed of sugars such as the biologically relevant preservative trehalose. Here, we compare the folding thermodynamics of a model miniprotein in solution and in the glassy state of the sugars trehalose and glucose. Using synchrotron radiation circular dichroism (SRCD), we find that the same native structure persists in solution and glass. However, upon transition to the glass, a completely different, conformationally restricted unfolded state replaces the disordered denatured state found in solution, potentially inhibiting misfolding. Concomitantly, a large exothermic contribution is observed in glass, exposing the stabilizing effect of interactions with the sugar matrix on the native state. Our results shed light on the mechanism of protein stabilization in sugar glass and should aid in future preservation technologies.


Assuntos
Conformação Proteica/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Proteínas/metabolismo , Trealose/química , Sequência de Aminoácidos , Dobramento de Proteína/efeitos dos fármacos , Proteínas/química , Termodinâmica , Vitrificação
10.
J Phys Chem Lett ; 12(32): 7708-7716, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34355897

RESUMO

NOx emission heavily affects our environment and human health. Photocatalytic denitrification (deNOx) attracted much attention because it is low-cost and nonpolluting, but undesired nitrite and nitrate were produced in reality, instead of harmless N2. Unveiling the active sites and the photocatalytic mechanism is very important to improve the process. Herein, we have employed a combinational scenario to investigate the reaction mechanism of NO2 and H2O on anatase TiO2(101). On the one hand, a polaron-corrected GGA functional (GGA + Lany-Zunger) was applied to improve the description of electronic states in photoassisted processes. On the other hand, a reaction phase diagram (RPD) was established to understand the (quasi) activity trend over both perfect and defective surfaces. It was found that a perfect surface is more active via the Eley-Rideal mechanism without NO2 adsorption, while the activity on defective surfaces is limited by the sluggish recombinative desorption. A photogenerated hole can weaken the OH* adsorption energies and circumvents the scaling relation of the dark reaction, eventually enhancing the deNOx activity significantly. The insights gained from our work indicate that tuning the reactivity by illumination-induced localized charge and diverse reaction pathways are two methods for improving adsorption, dissociation, and desorption processes to go beyond the conventional activity volcano plot limit of dark conditions.


Assuntos
Dióxido de Nitrogênio/química , Titânio/química , Adsorção , Catálise/efeitos da radiação , Cinética , Modelos Químicos , Termodinâmica , Titânio/efeitos da radiação , Raios Ultravioleta , Água/química
11.
J Phys Chem Lett ; 12(32): 7854-7858, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34380316

RESUMO

This work uses electrochemical quartz crystal microbalance methods to demonstrate the enantiospecific interaction between a magnetized surface and a chiral amino acid. The enantiospecific adsorption of chiral molecules (cysteine is used as a model) on a ferromagnetic surface is shown to arise from the kinetics of adsorption and not from a thermodynamic stabilization. Measurements of the Gibbs free energy of adsorption for different chiral forms of cysteine and different electrode magnetization states show no significant differences, whereas measurements of the adsorption and desorption kinetics reveal a strong dependence on the magnetization state of the electrode surface. In addition, the enantioselectivity is shown to depend sensitively on the solution pH and the charge state of the chiral adsorbate.


Assuntos
Cisteína/química , Imãs/química , Adsorção , Técnicas Eletroquímicas/instrumentação , Eletrodos , Cinética , Níquel/química , Técnicas de Microbalança de Cristal de Quartzo/instrumentação , Estereoisomerismo , Termodinâmica
12.
Anal Chem ; 93(35): 11982-11990, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34432422

RESUMO

An effective intensity-based reference is a cornerstone for quantitative nuclear magnetic resonance (NMR) studies, as the molecular concentration is encoded in its signal. In theory, NMR is well suited for the measurement of competitive protein adsorption onto nanoparticle (NP) surfaces, but current referencing systems are not optimized for multidimensional experiments. Presented herein is a simple and novel referencing system using 15N tryptophan (Trp) as an external reference for 1H-15N 2D NMR experiments. The referencing system is validated by the determination of the binding capacity of a single protein onto gold NPs. Then, the Trp reference is applied to protein mixtures, and signals from each protein are accurately quantified. All results are consistent with previous studies, but with substantially higher precision, indicating that the Trp reference can accurately calibrate the residue peak intensities and reduce systematic errors. Finally, the proposed Trp reference is used to kinetically monitor in situ and in real time the competitive adsorption of different proteins. As a challenging test case, we successfully apply our approach to a mixture of protein variants differing by only a single residue. Our results show that the binding of one protein will affect the binding of the other, leading to an altered NP corona composition. This work therefore highlights the importance of studying protein-NP interactions in protein mixtures in situ, and the referencing system developed here enables the quantification of binding kinetics and thermodynamics of multiple proteins using various 1H-15N 2D NMR techniques.


Assuntos
Nanopartículas , Proteínas , Adsorção , Espectroscopia de Ressonância Magnética , Termodinâmica
13.
Molecules ; 26(16)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34443382

RESUMO

The E-hook of ß-tubulin plays instrumental roles in cytoskeletal regulation and function. The last six C-terminal residues of the ßII isotype, a peptide of amino acid sequence EGEDEA, extend from the microtubule surface and have eluded characterization with classic X-ray crystallographic techniques. The band position of the characteristic amide I vibration of small peptide fragments is heavily dependent on the length of the peptide chain, the extent of intramolecular hydrogen bonding, and the overall polarity of the fragment. The dependence of the E residue's amide I ν(C=O) and the αCOO- terminal ν(C=O) bands on the neighboring side chain, the length of the peptide fragment, and the extent of intramolecular hydrogen bonding in the structure are investigated here via the EGEDEA peptide. The hexapeptide is broken down into fragments increasing in size from dipeptides to hexapeptides, including EG, ED, EA, EGE, EDE, DEA, EGED, EDEA, EGEDE, GEDEA, and, finally, EGEDEA, which are investigated with experimental Raman spectroscopy and density functional theory (DFT) computations to model the zwitterionic crystalline solids (in vacuo). The molecular geometries and Boltzmann sum of the simulated Raman spectra for a set of energetic minima corresponding to each peptide fragment are computed with full geometry optimizations and corresponding harmonic vibrational frequency computations at the B3LYP/6-311++G(2df,2pd) level of theory. In absence of the crystal structure, geometry sampling is performed to approximate solid phase behavior. Natural bond order (NBO) analyses are performed on each energetic minimum to quantify the magnitude of the intramolecular hydrogen bonds. The extent of the intramolecular charge transfer is dependent on the overall polarity of the fragment considered, with larger and more polar fragments exhibiting the greatest extent of intramolecular charge transfer. A steady blue shift arises when considering the amide I band position moving linearly from ED to EDE to EDEA to GEDEA and, finally, to EGEDEA. However, little variation is observed in the αCOO- ν(C=O) band position in this family of fragments.


Assuntos
Amidas/química , Teoria da Densidade Funcional , Ácido Glutâmico/química , Fragmentos de Peptídeos/química , Análise Espectral Raman , Simulação por Computador , Conformação Molecular , Estrutura Secundária de Proteína , Termodinâmica , Vibração
14.
Molecules ; 26(16)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34443680

RESUMO

Effect of temperature and pH on the interaction of curcumin with ß-casein was explored by fluorescence spectroscopy, ultraviolet-visible spectroscopy and molecular dynamics simulation. The spectroscopic results showed that curcumin could bind to ß-casein to form a complex which was driven mainly by electrostatic interaction. The intrinsic fluorescence of ß-casein was quenched by curcumin through static quenching mechanism. The binding constants of curcumin to ß-casein were 6.48 × 104 L/mol (298 K), 6.17 × 104 L/mol (305 K) and 5.73 × 104 L/mol (312 K) at pH 2.0, which was greater than that (3.98 × 104 L/mol at 298 K, 3.90 × 104 L/mol at 305 K and 3.41 × 104 L/mol at 312 K) at pH 7.4. Molecular docking study showed that binding energy of ß-casein-curcumin complex at pH 2.0 (-7.53 kcal/mol) was lower than that at pH 7.4 (-7.01 kcal/mol). The molecular dynamics simulation study showed that the binding energy (-131.07 kJ/mol) of ß-casein-curcumin complex was relatively low at pH 2.0 and 298 K. α-Helix content in ß-casein was decreased and random coil content was increased in the presence of curcumin. These results can promote a deep understanding of interaction between curcumin and ß-casein and provide a reference for improving the bioavailability of curcumin.


Assuntos
Caseínas/farmacologia , Curcumina/farmacologia , Simulação de Dinâmica Molecular , Análise Espectral , Caseínas/química , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Imageamento Tridimensional , Simulação de Acoplamento Molecular , Ligação Proteica , Estrutura Secundária de Proteína , Homologia Estrutural de Proteína , Termodinâmica
15.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361773

RESUMO

The thrombin binding aptamer (TBA) is a promising nucleic acid-based anticoagulant. We studied the effects of chemical modifications, such as dendrimer Trebler and NHS carboxy group, on TBA with respect to its structures and thrombin binding affinity. The two dendrimer modifications were incorporated into the TBA at the 5' end and the NHS carboxy group was added into the thymine residues in the thrombin binding site of the TBA G-quadruplex (at T4, T13 and both T4/T13) using solid phase oligonucleotide synthesis. Circular dichroism (CD) spectroscopy confirmed that all of these modified TBA variants fold into a stable G-quadruplex. The binding affinity of TBA variants with thrombin was measured by surface plasmon resonance (SPR). The binding patterns and equilibrium dissociation constants (KD) of the modified TBAs are very similar to that of the native TBA. Molecular dynamics simulations studies indicate that the additional interactions or stability enhancement introduced by the modifications are minimized either by the disruption of TBA-thrombin interactions or destabilization elsewhere in the aptamer, providing a rational explanation for our experimental data. Overall, this study identifies potential positions on the TBA that can be modified without adversely affecting its structure and thrombin binding preference, which could be useful in the design and development of more functional TBA analogues.


Assuntos
Anticoagulantes/síntese química , Aptâmeros de Nucleotídeos/síntese química , Quadruplex G , Oligonucleotídeos/síntese química , Trombina/química , Anticoagulantes/metabolismo , Anticoagulantes/farmacologia , Aptâmeros de Nucleotídeos/metabolismo , Aptâmeros de Nucleotídeos/farmacologia , Sequência de Bases , Sítios de Ligação , Coagulação Sanguínea/efeitos dos fármacos , Dendrímeros/química , Humanos , Cinética , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico , Oligonucleotídeos/metabolismo , Ligação Proteica , Termodinâmica , Trombina/antagonistas & inibidores , Trombina/metabolismo
16.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361778

RESUMO

Protein-ligand interaction analysis is important for drug discovery and rational protein design. The existing online tools adopt only a single conformation of the complex structure for calculating and displaying the interactions, whereas both protein residues and ligand molecules are flexible to some extent. The interactions evolved with time in the trajectories are of greater interest. MolADI is a user-friendly online tool which analyzes the protein-ligand interactions in detail for either a single structure or a trajectory. Interactions can be viewed easily with both 2D graphs and 3D representations. MolADI is available as a web application.


Assuntos
Receptor A2A de Adenosina/química , Bibliotecas de Moléculas Pequenas/química , Software , Sítios de Ligação , Humanos , Cinética , Ligantes , Modelos Moleculares , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteínas , Receptor A2A de Adenosina/metabolismo , Bibliotecas de Moléculas Pequenas/metabolismo , Especificidade por Substrato , Termodinâmica
17.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361791

RESUMO

As a key enzyme regulating postprandial blood glucose, α-Glucosidase is considered to be an effective target for the treatment of diabetes mellitus. In this study, a simple, rapid, and effective method for enzyme inhibitors screening assay was established based on α-glucosidase catalyzes reactions in a personal glucose meter (PGM). α-glucosidase catalyzes the hydrolysis of maltose to produce glucose, which triggers the reduction of ferricyanide (K3[Fe(CN)6]) to ferrocyanide (K4[Fe(CN)6]) and generates the PGM detectable signals. When the α-glucosidase inhibitor (such as acarbose) is added, the yield of glucose and the readout of PGM decreased accordingly. This method can achieve the direct determination of α-glucosidase activity by the PGM as simple as the blood glucose tests. Under the optimal experimental conditions, the developed method was applied to evaluate the inhibitory activity of thirty-four small-molecule compounds and eighteen medicinal plants extracts on α-glucosidase. The results exhibit that lithospermic acid (52.5 ± 3.0%) and protocatechualdehyde (36.8 ± 2.8%) have higher inhibitory activity than that of positive control acarbose (31.5 ± 2.5%) at the same final concentration of 5.0 mM. Besides, the lemon extract has a good inhibitory effect on α-glucosidase with a percentage of inhibition of 43.3 ± 3.5%. Finally, the binding sites and modes of four active small-molecule compounds to α-glucosidase were investigated by molecular docking analysis. These results indicate that the PGM method is feasible to screening inhibitors from natural products with simple and rapid operations.


Assuntos
Benzaldeídos/farmacologia , Benzofuranos/farmacologia , Glicemia/análise , Catecóis/farmacologia , Depsídeos/farmacologia , Diabetes Mellitus Tipo 2/diagnóstico , Inibidores de Glicosídeo Hidrolases/farmacologia , Monitorização Ambulatorial/métodos , alfa-Glucosidases/sangue , Acarbose/química , Acarbose/farmacologia , Benzaldeídos/química , Benzaldeídos/isolamento & purificação , Benzofuranos/química , Benzofuranos/isolamento & purificação , Sítios de Ligação , Técnicas Biossensoriais/instrumentação , Catecóis/química , Catecóis/isolamento & purificação , Depsídeos/química , Depsídeos/isolamento & purificação , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/química , Humanos , Hidrólise , Cinética , Maltose/metabolismo , Simulação de Acoplamento Molecular , Monitorização Ambulatorial/instrumentação , Extratos Vegetais/química , Plantas Medicinais , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Termodinâmica , Dispositivos Eletrônicos Vestíveis , alfa-Glucosidases/química
18.
Chem Pharm Bull (Tokyo) ; 69(8): 734-740, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34334517

RESUMO

Peptide bond formation in living cells occurs at the peptidyl transferase center (PTC) of the large ribosomal subunit and involves the transfer of the peptidyl group from peptidyl-tRNA to aminoacyl-tRNA. Despite numerous kinetic and theoretical studies, many details of this reaction -such as whether it proceeds via a stepwise or concerted mechanism- remain unclear. In this study, we calculated the geometry and energy of the transition states and intermediates in peptide bond formation in the PTC environment using the ONIOM (our own n-layered integrated molecular orbital and molecular mechanics) method. The calculations indicated that the energy of the transition states of stepwise mechanisms are lower than those of concerted mechanisms and suggested that the reaction involves a neutral tetrahedral intermediate that is stabilized through the hydrogen-bonding network in the PTC environment. The results will lead to a better understanding of the mechanism of peptidyl transfer reaction, and resolve fundamental questions of the steps and molecular intermediates involved in peptide bond formation in the ribosome.


Assuntos
Teoria da Densidade Funcional , Peptídeos/química , Ribossomos/química , Estrutura Molecular , Termodinâmica
19.
Chem Pharm Bull (Tokyo) ; 69(8): 789-795, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34334523

RESUMO

In this study, the effect of contact time, temperature, pH, and coexistences on the adsorption of phosphate ions using the complex nickel-aluminum-zirconium hydroxide (NAZ) was evaluated. Moreover, the recovery of adsorbed phosphate ions from NAZ using desorption solution with different concentrations was demonstrated. The results showed that the quantity of phosphate ions adsorbed gradually increased with time, and the adsorption equilibrium was achieved within 24 h after adsorption. This kinetic data could be well described by the pseudo-second-order model with the correlation coefficient in the value of 0.997. Additionally, the quantity of phosphate which was adsorbed increased as temperature increased, and these results corresponded well with both the Langmuir, the correlation coefficient ranged from 0.920-0.949, and Freundlich models, the correlation coefficient ranged from 0.863-0.995. These results showed that the adsorption of phosphate ion was monolayer adsorption onto the NAZ surface. The optimal pH for removal of phosphate ions from aqueous media was during 4-8. In addition, chloride, nitrate, and sulfate ions did not significantly affect to the adsorption capability of phosphate ions in the complex solution system. Finally, the phosphate ions which were adsorbed onto NAZ could be recovered using sodium sulfate solution (recovery percentage: approx. 50% using sodium sulfate solution at 1000 mmol/L). These results highlight the potential of using NAZ as the cost-effectiveness adsorbent for phosphate ions removal from aqueous media.


Assuntos
Alumínio/química , Hidróxidos/química , Níquel/química , Fosfatos/química , Zircônio/química , Adsorção , Concentração de Íons de Hidrogênio , Íons/química , Tamanho da Partícula , Propriedades de Superfície , Termodinâmica
20.
Nano Lett ; 21(17): 7159-7165, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34410717

RESUMO

The rapid development of state-of-the-art nanotechnology is driven by the emerging novel nanofabrication methods, such as self-rolling of 2D materials or nanosheets. Nonetheless, the traditional chemical etching-based "roll-up" technologies suffer from a low fabrication efficiency and generally produce only scroll-like structures. In this work, we develop a versatile, ultrafast, and etching-free method to synthesize self-rolled metallic nanostructures through hydrogel surface buckling enabled exfoliation, which enables rapid exfoliation and self-rolling of metallic nanosheets at a rate about 1 to 2 orders of magnitude faster than other methods. Furthermore, we observe a scroll-helix-scroll transition through the twisting of the self-rolled nanosheets. Through extensive finite element simulations and experiments, we reveal the thermodynamics underpinning these configurational transitions.


Assuntos
Nanoestruturas , Nanotecnologia , Termodinâmica
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