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1.
Enzyme Microb Technol ; 150: 109879, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34489032

RESUMO

The impact of hydrophilic polymers in an organosilica matrix on the features and performance of immobilized methylotrophic yeast cells used as biocatalysts was investigated and described. Yeast cells were immobilized in a matrix made of tetraethoxysilane (TEOS) and methyltriethoxysilane (MTES) by one-step sol-gel route of synthesis in the presence of polyethylene glycol (PEG) or polyvinyl alcohol (PVA). Organosilica shells were spontaneously built around cells as a result of yeast immobilization at a TEOS to MTES ratio of 85/15 vol% and hydrophilic polymer (PEG or PVA). As a structure-directing agent, PVA produces organosilica films. Stable high-performance biocatalysts active for one year, if stored at -18 °C, have been obtained by entrapment of methylotrophic yeast cells. A trickling biofilter with and without active aeration was designed using entrapped yeast cells to treat methanol polluted wastewater. A biofilter model with active aeration could halve methanol input thus demonstrating better performance compared to treatment without active aeration.


Assuntos
Polímeros , Saccharomyces cerevisiae , Biocatálise , Interações Hidrofóbicas e Hidrofílicas , Álcool de Polivinil
2.
Mater Sci Eng C Mater Biol Appl ; 128: 112268, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474827

RESUMO

Hydrogel coatings can improve the biocompatibility of medical devices. However, stable surface bonding and homogeneity of hydrogel coatings are often challenging. This study exploits the benefits of biohybrid hydrogels of crosslinked four-armed poly(ethylene glycol) and heparin to enhance the hemocompatibility of cobalt­chromium (CoCr) vascular stents. A bonding layer of dual silane and poly(ethylene-alt-maleic anhydride) (PEMA) treatment was applied to the stent to provide covalent immobilization and hydrophilicity for the homogeneous spreading of the hydrogel. A spray coating technology was used to distribute the aqueous solution of the reactive hydrogel precursors onto the sub-millimeter struts of the stents, where the solution polymerized to a homogeneous hydrogel film. The coating was mechanically stable on the stent after ethanol dehydration, and the stents could be stored in a dry state. The homogeneity and stability of the coating during stent expansion were verified. Quasistatic and dynamic whole blood incubation experiments showed substantial suppression of the pro-coagulant and inflammatory activity of the bare metal by the coating. Translation of the technology to industrial coating devices and future surface modification of stents with anti-inflammatory hydrogels are discussed.


Assuntos
Heparina , Hidrogéis , Interações Hidrofóbicas e Hidrofílicas , Polietilenoglicóis , Stents
3.
Nanoscale ; 13(32): 13758-13763, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34477650

RESUMO

Here, we report how the nature of the hydrophobic core affects the molecular interactions of DNA block copolymer assemblies. Three different amphiphilic DNA block copolymers, DNA-b-polystyrene (DNA-b-PS), DNA-b-poly(2-vinylpyridine) (DNA-b-P2VP), and DNA-b-poly(methyl acrylate) (DNA-b-PMA) were synthesized and assembled into spherical micelles composed of a hydrophobic polymer core and DNA corona. Interestingly, DNA block copolymer micelles having different hydrophobic cores exhibited markedly different molecular and biological interactions. DNA-b-PS exhibited higher melting temperature, sharper melting transition, higher stability to nuclease-catalyzed DNA degradation, and higher cellular uptake efficiency compared to DNA-b-P2VP and DNA-b-PMA. The investigation of the self-assembly behavior revealed a much higher aggregation number and DNA density for DNA-b-PS micelles, which explains the superior properties of DNA-b-PS. These results demonstrate that the type of the hydrophobic core polymer, which has been largely overlooked, has a profound impact on the molecular and biological interactions of the DNA shell.


Assuntos
Micelas , Polímeros , DNA , Interações Hidrofóbicas e Hidrofílicas , Poliestirenos
4.
Nanoscale ; 13(31): 13318-13327, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34477738

RESUMO

Investigation of the self-assembly of peptides is critically important to clarify certain biophysical phenomena, fulfill some biological functions, and construct functional materials. However, it is still a challenge to precisely predict the self-assembled structures of peptides because of their complicated driving forces and various assembling pathways. In this work, to elucidate the effects of noncovalent interactions including hydrogen bonding, molecular geometry, and hydrophobic and electrostatic interactions on the peptide self-assembly, a series of asymmetric bolaamphiphilic short peptides consisting of Ac-EI3K-NH2 (EI3K), Ac-EI4K-NH2 (EI4K), Ac-KI3E-NH2 (KI3E) and Ac-KI4E-NH2 (KI4E) were designed and their self-assembling behaviors at different solution pH values were investigated systematically. The peptides self-assembled into twisted nanofibers under most conditions except for EI4K in a strongly alkaline solution and KI4E under a strongly acidic condition, in which they self-assembled into nanotubes via helical monolayer nanosheet intermediates. In particular, KI4E nanotubes are formed under acidic conditions, and its diameters are ∼500 nm much greater than most of the self-assembled structures from bolaamphiphilic peptides. Moreover, reversible morphological transition between the nanotubes and twisted nanofibers was observed with the change in solution pH. Such tunable self-assembled structures and switchable surface properties of the asymmetric bolaamphiphilic short-peptides allow them to be used as templates to construct advanced materials. Silica and titania nanomaterials faithful to the peptide templates in morphology were prepared at ambient temperature. This work clearly elucidates the effects of noncovalent interactions on the peptide self-assembly and also provides new insights into the design and preparation of complicated inorganic materials from tunable organic templates.


Assuntos
Nanoestruturas , Dióxido de Silício , Interações Hidrofóbicas e Hidrofílicas , Peptídeos , Titânio
5.
Anal Chim Acta ; 1177: 338761, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34482887

RESUMO

Protein phosphorylation and glycosylation, which are closely related to various diseases, have been extensively studied recently. Mass spectrometry (MS) based phosphoproteomics and glycoproteomics analysis rely heavily on the pre-treatment. Due to the differences in enrichment conditions, there are still huge challenges in designing and preparing a single affinity material to achieve efficient simultaneous capture and elution of phosphopeptides and glycopeptides. Herein, a novel magnetic covalent organic framework, which was modified with functional molecule 4-(3-(2-(methacryloyloxy)ethyl)-ureido)benzoic acid (MUBA), was designed as a bifunctional enrichment platform for glycopeptides and phosphopeptides. Thanks to the multiple hydrogen bonding interactions between MUBA and hydrogen phosphates, the material possessed excellent enrichment performance for phosphopeptides. In addition, the hydrophilicity of the COF structure and modified molecules endowed this material recognition capability towards glycopeptides based on hydrophilic interaction chromatography. Combining with the inherent properties of COF structure, the established platform achieved simultaneous enrichment of phosphopeptides and glycopeptides with excellent selectivity (1:1:1000 M ratio of α-casein/IgG/BSA), high sensitivity (0.05 fmol/µL α-casein; 0.05 fmol/µL IgG), and good size-exclusion effect (α-casein digests/IgG digests/BSA, 1:1:500). More excitingly, the method was used for the identification of glycopeptides and phosphopeptides from rat liver tissue and the exosomes extracted from liver cancer patients' plasma, proving its specific phosphoproteomics and glycoproteomics study in complex biosamples.


Assuntos
Estruturas Metalorgânicas , Fosfopeptídeos , Animais , Glicopeptídeos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Fenômenos Magnéticos , Magnetismo , Ratos
6.
Se Pu ; 39(9): 981-988, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34486837

RESUMO

Protein glycosylation is among the most common and important post-translational modifications, and plays an important regulatory role in many biological processes, including signal transduction, protein translation, and immune response. Abnormal protein glycosylation is also associated with numerous diseases, suggesting that glycoproteins may offer an array of useful disease biomarkers. Mass spectrometry (MS) has become an important analytical tool in glycoproteomics. However, the low abundance and weak ionization efficiency of glycopeptides have hindered direct mass spectrometric analyses, which remain considerably challenging. Glycoprotein and glycopeptide enrichment from complex biological samples is an important step in glycoproteomics. Diverse methods have recently been developed for specific glycoprotein and glycopeptide enrichment, including hydrophilic interaction liquid chromatography (HILIC), lectin affinity chromatography, boronate affinity chromatography, and hydrazide functional affinity chromatography. A variety of enrichment materials designed for the above strategies have been developed to meet the requirement of enriching low abundance glycoproteins and glycopeptides in complex samples. Magnetic solid phase extraction (MSPE) is an efficient sample pretreatment technology that offers advantages of simple operation, low cost, and high extraction efficiency. Functionalized magnetic nanomaterials have been widely used as adsorbents in glycoproteome studies. Since magnetic adsorbent is a key factor in MSPE, in this review, the preparation of magnetic nanomaterials functionalized with sugars, ionic liquids, lectins, boronate affinity ligands, metal organic frameworks, and covalent organic frameworks, and their applications in glycoprotein and glycopeptide enrichment are summarized. These functional magnetic nanomaterials possess high specific surface area and a large number of active adsorption sites, allowing different enrichment mechanisms, including HILIC, lectin affinity chromatography, and boronate and hydrazide functional affinity chromatography. These functional magnetic nanomaterials are mainly used to enrich glycoproteins and glycopeptides in serum, plasma, cells, tissues, saliva and other biological samples. Nearly 90 papers published in the last decade from the Science Citation Index (SCI) and Chinese core journals have been cited in this paper. Finally, the development and prospects of magnetic nanomaterials in glycoprotein and glycopeptide enrichment are also discussed.


Assuntos
Glicopeptídeos , Nanoestruturas , Glicoproteínas , Interações Hidrofóbicas e Hidrofílicas , Fenômenos Magnéticos , Proteoma
7.
Macromol Rapid Commun ; 42(17): e2100311, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34355439

RESUMO

Polyacrylates bearing long fluoroalkyl (Rf) side chains are known to have ultralow surface energies that are appropriate for functional coating and fabric finishing. However, these long Rf chains cause health concerns because of the risk of toxic and bioaccumulative perfluoroalcanoic acid emission via oxidative degradation. This work demonstrates that incorporating a short Rf chain of perfluoroethylene at the end of the side chains of syndiotactic poly(substituted methylene) (PM) produces hydrophobicity. A contact angle of 105° of PM remains constant for more than 50 s, whereas that of the polyacrylate (PA) with the same side chain rapidly decreases from 85° to 44° over the same period. Such persistent water repellency of the PM is ascribed to a liquid crystal structure comprised the main chains arranged in a 2D hexagonal lattice and side chains that extend perpendicularly from these main chains.


Assuntos
Cristais Líquidos , Água , Interações Hidrofóbicas e Hidrofílicas
8.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360878

RESUMO

Sigma-1 receptor (S1R) is an intracellular, multi-functional, ligand operated protein that also acts as a chaperone. It is considered as a pluripotent drug target in several pathologies. The publication of agonist and antagonist bound receptor structures has paved the way for receptor-based in silico drug design. However, recent studies on this subject payed no attention to the structural differences of agonist and antagonist binding. In this work, we have developed a new ensemble docking-based virtual screening protocol utilizing both agonist and antagonist bound S1R structures. This protocol was used to screen our in-house compound library. The S1R binding affinities of the 40 highest ranked compounds were measured in competitive radioligand binding assays and the sigma-2 receptor (S2R) affinities of the best S1R binders were also determined. This way three novel high affinity S1R ligands were identified and one of them exhibited a notable S1R/S2R selectivity.


Assuntos
Isoxazóis/química , Simulação de Acoplamento Molecular/métodos , Pentazocina/química , Piridinas/química , Receptores sigma/química , Sítios de Ligação , Interações Hidrofóbicas e Hidrofílicas , Isoxazóis/análise , Isoxazóis/farmacologia , Ligantes , Estrutura Molecular , Pentazocina/análise , Pentazocina/farmacologia , Ligação Proteica , Piridinas/análise , Piridinas/farmacologia , Ensaio Radioligante/métodos , Receptores sigma/agonistas , Receptores sigma/análise , Receptores sigma/antagonistas & inibidores
9.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360886

RESUMO

Xanthine oxidase (XO) is an important target for the effective treatment of hyperuricemia-associated diseases. A series of novel 2-substituted 6-oxo-1,6-dihydropyrimidine-5-carboxylic acids (ODCs) as XO inhibitors (XOIs) with remarkable activities have been reported recently. To better understand the key pharmacological characteristics of these XOIs and explore more hit compounds, in the present study, the three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, pharmacophore modeling, and molecular dynamics (MD) studies were performed on 46 ODCs. The constructed 3D-QSAR models exhibited reliable predictability with satisfactory validation parameters, including q2 = 0.897, R2 = 0.983, rpred2 = 0.948 in a CoMFA model, and q2 = 0.922, R2 = 0.990, rpred2 = 0.840 in a CoMSIA model. Docking and MD simulations further gave insights into the binding modes of these ODCs with the XO protein. The results indicated that key residues Glu802, Arg880, Asn768, Thr1010, Phe914, and Phe1009 could interact with ODCs by hydrogen bonds, π-π stackings, or hydrophobic interactions, which might be significant for the activity of these XOIs. Four potential hits were virtually screened out using the constructed pharmacophore model in combination with molecular dockings and ADME predictions. The four hits were also found to be relatively stable in the binding pocket by MD simulations. The results in this study might provide effective information for the design and development of novel XOIs.


Assuntos
Ácidos Carboxílicos/química , Inibidores Enzimáticos/química , Simulação de Acoplamento Molecular/métodos , Simulação de Dinâmica Molecular , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/química , Desenho de Fármacos , Inibidores Enzimáticos/uso terapêutico , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Hiperuricemia/tratamento farmacológico , Estrutura Molecular , Ligação Proteica , Relação Quantitativa Estrutura-Atividade
10.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361760

RESUMO

Self-assembly is the most powerful force for creating ordered supramolecular architectures from simple components under mild conditions. π···π stacking interactions have been widely explored in modern supramolecular chemistry as an attractive reversible noncovalent tool for the nondestructive fabrication of materials for different applications. Here, we report on the self-assembly of cytidine 5'-monophosphate (CMP) nucleotide and copper metal ions for the preparation of a rare nanoporous supramolecular metal-organic framework in water. π···π stacking interactions involving the aromatic groups of the ancillary 2,2'-bipyridine (bipy) ligands drive the self-assemblies of hexameric pseudo-amphiphilic [Cu6(bipy)6(CMP)2(µ-O)Br4]2+ units. Owing to the supramolecular geometric matching between the aromatic tails, a nanoporous crystalline phase with hydrophobic and hydrophilic chiral pores of 1.2 and 0.8 nanometers, respectively, was successfully synthesized. The encoded chiral information, contained on the enantiopure building blocks, is transferred to the final supramolecular structure, assembled in the very unusual topology 8T6. These kinds of materials, owing to chiral channels with chiral active sites from ribose moieties, where the enantioselective recognition can occur, are, in principle, good candidates to carry out efficient separation of enantiomers, better than traditional inorganic and organic porous materials.


Assuntos
2,2'-Dipiridil/química , Cobre/química , Citidina Monofosfato/química , Estruturas Metalorgânicas/síntese química , Cristalização , Cristalografia por Raios X , Interações Hidrofóbicas e Hidrofílicas , Estruturas Metalorgânicas/química , Estrutura Molecular , Porosidade , Soluções , Estereoisomerismo
11.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361761

RESUMO

Cocaine toxicity has been a subject of study because cocaine is one of the most common and potent drugs of abuse. In the current study the effect of cocaine on human liver cancer cell line (HepG2) was assessed. Cocaine toxicity (IC50) on HepG2 cells was experimentally calculated using an XTT assay at 2.428 mM. The metabolic profile of HepG2 cells was further evaluated to investigate the cytotoxic activity of cocaine at 2 mM at three different time points. Cell medium and intracellular material samples were analyzed with a validated HILIC-MS/MS method for targeted metabolomics on an ACQUITY Amide column in gradient mode with detection on a triple quadrupole mass spectrometer in multiple reaction monitoring. About 106 hydrophilic metabolites from different metabolic pathways were monitored. Multivariate analysis clearly separated the studied groups (cocaine-treated and control samples) and revealed potential biomarkers in the extracellular and intracellular samples. A predominant effect of cocaine administration on alanine, aspartate, and glutamate metabolic pathway was observed. Moreover, taurine and hypotaurine metabolism were found to be affected in cocaine-treated cells. Targeted metabolomics managed to reveal metabolic changes upon cocaine administration, however deciphering the exact cocaine cytotoxic mechanism is still challenging.


Assuntos
Alanina/metabolismo , Ácido Aspártico/metabolismo , Cocaína/toxicidade , Ácido Glutâmico/metabolismo , Metaboloma/efeitos dos fármacos , Biomarcadores/metabolismo , Cromatografia Líquida , Células Hep G2 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Redes e Vias Metabólicas , Metabolômica/métodos , Análise Multivariada , Espectrometria de Massas em Tandem , Taurina/análogos & derivados , Taurina/metabolismo
12.
Inorg Chem ; 60(16): 12610-12620, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34351146

RESUMO

Herein, we report a new series of bifunctional chelators (BFCs) with a high affinity for amyloid aggregates, a strong binding affinity toward Cu(II), and favorable lipophilicity for potential blood-brain barrier penetration. The alkyl carboxylate ester pendant arms offer up to 3 orders of magnitude higher binding affinity toward Cu(II) and enable the BFCs to form stable 64Cu-radiolabeled complexes. Among the five compounds tested, the 64Cu-YW-7 and 64Cu-YW-10 complexes exhibit strong and specific staining of amyloid plaques in ex vivo autoradiography studies. Importantly, these BFCs have promising partition coefficient (log Doct) values of 0.91-1.26 and show some brain uptake in biodistribution studies using CD-1 mice. Overall, these BFCs could serve as lead compounds for the development of positron emission tomography imaging agents for AD diagnosis.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Quelantes/química , Quelantes/metabolismo , Radioisótopos de Cobre , Interações Hidrofóbicas e Hidrofílicas , Tomografia por Emissão de Pósitrons , Doença de Alzheimer/metabolismo , Barreira Hematoencefálica/metabolismo
13.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3198-3204, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396737

RESUMO

Indigo Naturalis( IN) is mainly composed of 10% organic matter and 90% inorganic matter,with a poor wettability and strong hydrophobicity. Indigo,indirubin and effective ingredients are almost insoluble in water. And how it exerts its effect after oral administration still needs to be revealed. For this reason,this study put forward the hypothesis that " Indigo Naturalis forms a slightly soluble calcium carbonate carrier in a strong acid environment of gastric fluid,and organic substances are solubilized in the bile environment of intestinal fluid",and then verified the hypothesis. First,the dissolution apparatus was used to simulate the change process of IN in different digestive fluid,and the effects of low-dose and normal bile on the dissolution of inorganic substances and the release of organic substances were compared. After the surface morphology and element changes of IN in different digestive fluid were observed,it was found that bile is the key to promoting the dissolution of organic and inorganic substances in IN. Furthermore,the rat fever model induced by 2,4-dinitrophenol was used to study the antipyretic effect of IN in normal rats and bile duct ligation rats. It was found that the antipyretic effect of IN on normal rats was better than that of bile duct ligation rats. The above results indicated that after oral administration of IN,the calcium carbonate carrier was transformed into a slightly soluble state in acidic gastric fluid,and a small amount of organic matter was released. When IN entered the intestinal fluid mixed with bile,the carrier dissolved in a large amount,and indigo and indirubin were dissolved in a large amount,so as to absorb the blood and exert the effect. This study has a certain significance for guiding clinical application of IN. For patients with insufficient bile secretion( such as bile duct resection),oral administration with IN may not be effective and shall be paid attention.


Assuntos
Índigo Carmim , Indigofera , Animais , Bile , Humanos , Interações Hidrofóbicas e Hidrofílicas , Extratos Vegetais , Ratos
14.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3213-3221, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396739

RESUMO

Polyethylene glycol (PEG) surface film-forming method was used to prepare hydrophilic Indigo Naturalis decoction pieces with stable effect.The preparation process of modified Indigo Naturalis was optimized and its microscopic properties,hydrophilicity,antipyretic efficacy,and safety were systematically evaluated.With equilibrium contact angle as assessment index,the influence of modifier type,modifier dosage,dispersant dosage,and co-grinding time on water solubility of Indigo Naturalis was investigated by single factor test.The results showed that the optimal preparation process was as follows.The 6%PEG6000 is dissolved in 10%anhydrous ethanol solution by sonification and then the mixture is ground with Indigo Naturalis for 2 min.The resultant product is dried on a square tray in an oven at 60℃to remove ethanol and thereby the PEG-modified hydrophilic Indigo Naturalis decoction pieces are yielded.The morphological observation under scanning electron microscope (SEM) indicated that the modified Indigo Naturalis had smoother surface than Indigo Naturalis,and energy spectrometer measurement showed that the nitrogen (N),calcium(Ca),oxygen (O),and silicon (Si) on the surface of modified Indigo Naturalis powder were less than those of Indigo Naturalis powder.Modified Indigo Naturalis had the equilibrium contact angle 18.96°smaller,polar component 22.222 m J·m~(-2)more,and nonpolar component 7.277 m J·m~(-2)smaller than the Indigo Naturalis powder.Multiple light scattering technique was employed to evaluate the dispersion in water and the result demonstrated that the transmittance of Indigo Naturalis and modified Indigo Naturalis was about85%and 75%,respectively,suggesting the higher dispersity of modified Indigo Naturalis.The suspension rate of modified Indigo Naturalis in water was determined by reflux treatment.The result showed that 57%of Indigo Naturalis was not wetted after refluxing for1 h,while the modified Indigo Naturalis was all wetted and dispersed into water.The dissolution of indigo and indirubin of modified Indigo Naturalis increased and the process was more stable.Then,rats were randomized into the blank group,model group,acetaminophen group,Indigo Naturalis group,and hydrophilic Indigo Naturalis group.The temperature changes of rats were observed after administration and the concentration of IL-1ßand TNF-αin serum and IL-1ßand PGE_2in hypothalamus was measured.The results indicated that the temperature of Indigo Naturalis group and hydrophilic Indigo Naturalis group dropped and the IL-1ßlevel of the hydrophilic Indigo Naturalis group decreased (P<0.05) as compared with those in the model group.Thus,both Indigo Naturalis and hydrophilic Indigo Naturalis had antipyretic effect,particularly the hydrophilic Indigo Naturalis.The acute toxicity test of hydrophilic Indigo Naturalis verified that it had no toxicity to rats.In this study,the hydrophilic Indigo Naturalis decoction pieces were prepared with the PEG surface film-forming method,and the antipyretic efficacy and safety were evaluated,which expanded the technological means of powder modification for Chinese medicine and provided a method for clinical use of Chinese medicine.


Assuntos
Medicamentos de Ervas Chinesas , Indigofera , Animais , Interações Hidrofóbicas e Hidrofílicas , Índigo Carmim , Polietilenoglicóis , Ratos
15.
Nat Commun ; 12(1): 4905, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385458

RESUMO

α-ketoglutarate (KG), also referred to as 2-oxoglutarate, is a key intermediate of cellular metabolism with pleiotropic functions. Cell-permeable esterified analogs are widely used to study how KG fuels bioenergetic and amino acid metabolism and DNA, RNA, and protein hydroxylation reactions, as cellular membranes are thought to be impermeable to KG. Here we show that esterified KG analogs rapidly hydrolyze in aqueous media, yielding KG that, in contrast to prevailing assumptions, imports into many cell lines. Esterified KG analogs exhibit spurious KG-independent effects on cellular metabolism, including extracellular acidification, arising from rapid hydrolysis and de-protonation of α-ketoesters, and significant analog-specific inhibitory effects on glycolysis or mitochondrial respiration. We observe that imported KG decarboxylates to succinate in the cytosol and contributes minimally to mitochondrial metabolism in many cell lines cultured in normal conditions. These findings demonstrate that nuclear and cytosolic KG-dependent reactions may derive KG from functionally distinct subcellular pools and sources.


Assuntos
Aminoácidos/metabolismo , Metabolismo Energético , Ésteres/metabolismo , Ácidos Cetoglutáricos/metabolismo , Mitocôndrias/metabolismo , Ácido Succínico/metabolismo , Animais , Linhagem Celular Tumoral , Citosol/metabolismo , Ésteres/química , Glicólise , Células HEK293 , Humanos , Hidrólise , Interações Hidrofóbicas e Hidrofílicas , Ácidos Cetoglutáricos/química , Camundongos , Consumo de Oxigênio , Células RAW 264.7
16.
J Agric Food Chem ; 69(34): 9957-9967, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34410117

RESUMO

We previously found that the immune response to haptens is positively correlated with molecular hydrophobicity. The antibodies used in immunoassays for capsaicinoids (CPCs) in waste oil suffer from low affinity and loose recognition to structural analogues. To address this issue, four new haptens (hapten1-4), maximally exposing the hydrophobic alkane chain (noncommon moiety of CPCs), were designed and expected to produce antibodies with high affinity and accurate recognition to CPCs based upon our findings. The assumption was first evidenced by computational chemistry and animal immunization successively. Compared with four reported haptens (hapten5-8) that expose the hydrophilic vanillyl amide moiety (common structure of CPCs and other vanillin alkaloids), antisera from hapten1-4 showed an approximately 1000-fold increase in affinity and significantly improved recognition profiles for CPCs. The molecular recognition study showed that the high affinity of the antibody from new haptens mainly originated from hydrophobic forces. An indirect competitive enzyme-linked immunosorbent assay based on a monoclonal antibody from hapten1 was developed and exhibited limits of detection as low as 0.73-3.29 µg/kg for four CPCs in oils and with insignificant cross-reactivities for other eight vanillin alkaloids, which have been never achieved in previous reports.


Assuntos
Química Computacional , Haptenos , Animais , Anticorpos Monoclonais , Ensaio de Imunoadsorção Enzimática , Interações Hidrofóbicas e Hidrofílicas , Imunoensaio
17.
J Agric Food Chem ; 69(34): 9905-9914, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34412476

RESUMO

Pea protein isolate nanoparticles (PPINs) were successfully prepared by potassium metabisulfite (K2S2O5). The disulfide bonds were disrupted by K2S2O5, and then the PPINs were formed through self-assembly. The average diameter of PPINs increased from 124.7 to 297.5 nm as the concentration of K2S2O5 was increased from 2 to 8 mM, and the PPINs showed higher ζ-potentials (-32.2 to -35.8 mV) and unimodal distribution. The content of free sulfhydryl groups first increased and then decreased with the fracture and reformation of disulfide bonds. Subsequently, the increase of the ß-sheet, which has considerable hydrophobicity, promoted the formation of PPINs. The formation mechanism of PPINs was explored by dissociation tests: hydrophobic interactions maintained the basic skeleton of PPINs, disulfide bonds stabilized the internal structure, and hydrogen bonds existed on the exterior of the particles. This study provided a simple and economical method to fabricate nanoparticles.


Assuntos
Nanopartículas , Proteínas de Ervilha , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas
18.
J Environ Sci (China) ; 107: 111-123, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34412774

RESUMO

A series of highly-hydrophobic MIL-53-Al (MIL = Materials of Institut Lavoisier) frameworks synthesized via decoration of the Al-OH groups by alkyl phosphonic acid were developed as adsorbents for removing acetone from humid gas streams. The newly prepared materials were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), N2 adsorption-desorption and thermogravimetric analysis (TGA). Their adsorption behaviors toward acetone vapor under dry and wet conditions were studied subsequently. Results showed that alkyl phosphonic acid was successfully grafted into MIL-53-Al skeleton through coordinating interaction with Al3+ generating MIL-53-Al@Cx (x = 12, 14, 18). The MIL-53-Al@Cx exhibited similar crystal structure and thermal stability to parent MIL-53-Al. Furthermore, the modified materials showed significantly enhanced hydrophobicity. The water vapor uptake of MIL-53-Al@C14 decreased by 72.55% at 75% relative humidity (RH). Dynamic adsorption experiments demonstrated that water vapor had almost no effect on the acetone adsorption performance of MIL-53-Al@C14. Under the condition of 90% RH, the acetone adsorption capacity of MIL-53-Al@C14 was 102.98% higher than that of MIL-53-Al. Notably, MIL-53-Al@C14 presented excellent adsorption reversibility and regeneration performance in 10 adsorption-desorption cycles. Taken together, the strategy of metal-OH group modification is an attractive way to improve the acetone adsorption performance over metal-organic frameworks (MOFs) under humid conditions. Besides, MIL-53-Al@C14 would be deemed as a promising candidate for capturing acetone in high moisture environment.


Assuntos
Acetona , Adsorção , Interações Hidrofóbicas e Hidrofílicas , Dietilamida do Ácido Lisérgico/análogos & derivados , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Phys Chem Chem Phys ; 23(33): 18001-18011, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34382985

RESUMO

A hydrophobic heptapeptide, with sequence AFILPTG, as part of a phage capsid protein binds effectively to silica particles carrying negative charge. Here, we explore the silica binding activity of the sequence as a short polypeptide with polar N and C terminals. To describe the structural changes that occur on binding, we fit experimental infrared, Raman and circular dichroism data for a number of structures simulated in the full configuration space of the hepta-peptide using replica exchange molecular dynamics. Quantum chemistry was used to compute normal modes of infrared and Raman spectra and establish a relationship to structures from MD data. To interpret the circular dichroism data, instead of empirical factoring of optical activity into helical/sheet/random components, we exploit natural transition orbital theory and specify the contributions of backbone amide units, side chain functional groups, water, sodium ions and silica to the observed transitions. Computed optical responses suggest a less folded backbone and importance of the N-terminal when close to silica. We further discuss the thermodynamics of the interplay of charged and hydrophobic moieties of the polypeptide on association with the silica surface. The outcomes of this study may assist in the engineering of novel artificial bio-silica heterostructures.


Assuntos
Oligopeptídeos/química , Dióxido de Silício/química , Teoria da Densidade Funcional , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Desdobramento de Proteína , Dióxido de Silício/síntese química , Propriedades de Superfície
20.
Appl Microbiol Biotechnol ; 105(14-15): 5873-5882, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34342711

RESUMO

(S)-4-Chlorophenylpyridylmethanol and (R)-4-chlorobenzhydrol are key pharmaceutical intermediates for the synthesis of bepotastine and cloperastine, respectively. However, the biocatalytic approach to prepare these bulky diaryl ketones remains challenging because of the low activity of naturally occurring alcohol dehydrogenases (ADH). In the present study, ADH seq5, which has an adequate binding pocket volume and accepts bulky diaryl ketones, was further engineered with a binding pocket of increased hydrophobicity. Based on molecular simulation and binding free energy analyses, a small mutation library was constructed, and mutant seq5-D150I with a threefold increase in kcat and a low Km was obtained successfully. The comparison of kinetic parameters, binding free energy, docking conformation, and critical catalytic distances calculated by molecular dynamic simulations revealed the source of increased activity. To develop a practical approach with seq5-D150I, reaction conditions including pH, temperature, buffer, and metal ions were optimised and applied to synthesise (S)-4-chlorophenylpyridylmethanol and (R)-4-chlorobenzhydrol with high enantiomeric excess. The space-time yields for (S)-4-chlorophenylpyridylmethanol and (R)-4-chlorobenzhydrol increased dramatically to as high as 263.4 g∙L-1 day-1 and 150 g∙L-1 day-1, respectively, which, to our knowledge, is the highest reported yield to date. These results show that the biocatalytic approach with seq5-D150I may be practical for future industrial applications.Key points An alcohol dehydrogenase was engineered based on binding free energy analysis. The mutant seq5-D150I obtained a threefold increase in kcat and a low Km. Two important pharmaceutical intermediates were obtained with high space-time yield.


Assuntos
Álcool Desidrogenase , Piperidinas , Álcool Desidrogenase/genética , Álcool Desidrogenase/metabolismo , Biocatálise , Interações Hidrofóbicas e Hidrofílicas , Cinética , Piridinas , Estereoisomerismo
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