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1.
Nucleic Acids Res ; 49(2): 1033-1045, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33367793

RESUMO

Diversity-generating retroelements (DGRs) vary protein sequences to the greatest extent known in the natural world. These elements are encoded by constituents of the human microbiome and the microbial 'dark matter'. Variation occurs through adenine-mutagenesis, in which genetic information in RNA is reverse transcribed faithfully to cDNA for all template bases but adenine. We investigated the determinants of adenine-mutagenesis in the prototypical Bordetella bacteriophage DGR through an in vitro system composed of the reverse transcriptase bRT, Avd protein, and a specific RNA. We found that the catalytic efficiency for correct incorporation during reverse transcription by the bRT-Avd complex was strikingly low for all template bases, with the lowest occurring for adenine. Misincorporation across a template adenine was only somewhat lower in efficiency than correct incorporation. We found that the C6, but not the N1 or C2, purine substituent was a key determinant of adenine-mutagenesis. bRT-Avd was insensitive to the C6 amine of adenine but recognized the C6 carbonyl of guanine. We also identified two bRT amino acids predicted to nonspecifically contact incoming dNTPs, R74 and I181, as promoters of adenine-mutagenesis. Our results suggest that the overall low catalytic efficiency of bRT-Avd is intimately tied to its ability to carry out adenine-mutagenesis.


Assuntos
Adenina , Bacteriófagos/genética , Mutagênese , Retroelementos/genética , Adenina/química , Arginina/química , Sequência de Bases , Bordetella/virologia , Catálise , Sistema Livre de Células , Simulação por Computador , DNA Complementar/genética , Glicina/química , Sequenciamento de Nucleotídeos em Larga Escala , Modelos Moleculares , Conformação Proteica , DNA Polimerase Dirigida por RNA/metabolismo , Proteínas Recombinantes/metabolismo
2.
Chemosphere ; 263: 127979, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32841877

RESUMO

Glyphosate (PMG) has been the most widely used herbicide in the world, and its environmental mobility and fate are mainly controlled by interactions with mineral surfaces. In soil systems, kaolinite is typically associated with humic acids (HAs) in the form of mineral-HA complexes, and hence it is crucial to characterize the molecular-scale interactions that occur between PMG and kaolinite and kaolinite-HA complexes. Batch experiments, Fourier transform infrared spectrum (FTIR) and X-ray photoelectron spectroscopy (XPS), isothermal titration calorimetry (ITC), and molecular dynamics (MD) simulations were performed to decipher the molecular interactions between PMG and kaolinite and kaolinite-HA composites. Our results reveal that kaolinite-HA composites adsorb higher concentrations of PMG than does kaolinite alone, likely due to more adsorption sites existed on kaolinite-HA than on kaolinite. FTIR and XPS analysis reveal that the carboxyl, phosphonyl and amino groups of PMG interacted with kaolinite and kaolinite-humic acid via Hydrogen bonds. The ITC results and interaction energy calculations indicate that the adsorption of PMG onto the kaolinite-HA is more energetically favorable relative to that onto kaolinite. MD simulations suggest that the PMG molecule adsorbs parallel to the surface of kaolinite and the composites through hydrogen bonding. Humic acid increases the adsorption of PMG through the creation of H-bond networks between PMG, the kaolinite surface, and humic acid. The results from this study improve our molecular-level understanding of the interactions between PMG and two important components of soil systems, and hence yield valuable information for characterizing the fate and behavior of PMG in soil environments.


Assuntos
Glicina/análogos & derivados , Herbicidas/química , Substâncias Húmicas , Caulim/química , Adsorção , Calorimetria , Glicina/química , Concentração de Íons de Hidrogênio , Minerais/química , Simulação de Dinâmica Molecular , Espectroscopia Fotoeletrônica , Solo , Espectroscopia de Infravermelho com Transformada de Fourier
3.
Food Chem ; 338: 128133, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33091994

RESUMO

Glyphosate (GLYP) was the most widely used broad-spectrum herbicide in the world. Herein, a gold nanoparticle (AuNP) probe dual-functionalized with anti-GLYP antibody and double-stranded oligonucleotides was synthesized. An AuNP-based bio-barcode immuno-PCR (AuNP-BB-iPCR) based on the probe was developed for sensitive detection of GLYP in food samples without high-cost and time-consuming experiments. GLYP detection was accomplished with a linear range from 61.1 pg g-1 to 31.3 ng g-1 and a detection limit of 4.5 pg g-1 which was 7 orders of magnitude lower than that of conventional ELISA (70 µg g-1) developed using the same antibody. The recoveries of GLYP from soybean, cole and maize samples were 99.8%, 102.6% and 103.7%, respectively, and all relative standard deviation values were below 12.9%. The assay time (including food samples preparation) of AuNP-BB-iPCR was 4 h. The proposed AuNP-BB-iPCR exhibits potential for sensitive detection of GLYP in foodstuffs and environment.


Assuntos
Glicina/análogos & derivados , Ouro/química , Imunoensaio/métodos , Nanopartículas Metálicas/química , Reação em Cadeia da Polimerase/métodos , Glicina/análise , Glicina/química , Humanos
4.
Food Chem ; 339: 128024, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152860

RESUMO

The aim of this study was to increase the baked flavour of low-acrylamide potato products. Strecker aldehydes and pyrazines make an important contribution to the flavour of potato products and are formed alongside acrylamide in the Maillard reaction. However, the Maillard reaction can be directed in favour of aroma formation by selecting appropriate precursors and intermediates based on the fundamental chemistry involved. Selected precursors were added to potato dough prior to baking. Addition of glycine and alanine together doubled high impact pyrazines and addition of 2,3-pentanedione or 3,4-hexanedione also promoted the formation of key trisubstituted pyrazines. Quantitative descriptive profiling of sensory attributes indicated that baked flavour was increased most when both Strecker aldehydes and pyrazines were increased together. This work shows that it is possible to enhance baked flavour in low-acrylamide products by adding a specifically targeted combination of amino acids and key intermediates, without increasing acrylamide concentration.


Assuntos
Acrilamida/análise , Culinária , Solanum tuberosum/química , Paladar , Aldeídos/química , Glicina/química , Reação de Maillard , Odorantes
5.
Nat Commun ; 11(1): 4348, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859910

RESUMO

The interpretation of molecular vibrational spectroscopic signals in terms of atomic motion is essential to understand molecular mechanisms and for chemical characterization. The signals are usually assigned after harmonic normal mode analysis, even if molecular vibrations are known to be anharmonic. Here we obtain the quantum anharmonic vibrational eigenfunctions of the 11-atom protonated glycine molecule and we calculate the density distribution of its nuclei and its geometry parameters, for both the ground and the O-H stretch excited states, using our semiclassical method based on ab initio molecular dynamics trajectories. Our quantum mechanical results describe a molecule elongated and more flexible with respect to what previously thought. More importantly, our method is able to assign each spectral peak in vibrational spectroscopy by showing quantitatively how normal modes involving different functional groups cooperate to originate that spectroscopic signal. The method will possibly allow for a better rationalization of experimental spectroscopy.


Assuntos
Glicina/química , Simulação de Dinâmica Molecular , Vibração , Estrutura Molecular , Teoria Quântica , Espectrofotometria Infravermelho , Termodinâmica
6.
J Oleo Sci ; 69(8): 883-891, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32641611

RESUMO

Ion specific effect, which is also known as Hofmeister effect, has been reported in numerous systems including ionic surfactant aggregates. Acyl amino acid surfactants have attracted growing attentions in the field of novel surfactants research due to their environmentally benign characteristics. The objective of this study was to investigate the effect of different salts containing NH4+ and tetraalkylammonium (TAA+), where alkyl = methyl (TMA+), ethyl (TEA+), and propyl (TPA+), cations on the dilational rheological properties of interfacial film are stabilized by potassium N-cocoyl glycinate (KCGl). The interfacial behaviors were studied using oscillating drop shape analysis method. The interfacial tensions (IFTs) and dilational rheological parameters results illustrate that KCGl in the presence of salts has better interfacial activity and stronger intermolecular interaction, indicating that added cations contribute to denser molecular packing at oil-water interface. Ion specific effects were observed in the system. Among the cations, KCGl shows highest dilational modulus in the presence of NH4+. The overall interaction between cations and headgroups of KCGl decreases in the sequence NH4+ >TMA+ >TEA+ ≈TPA+, which follows Hofmeister series. The increasing hydrophobicity of TAA+ prevents the interaction between cations and KCGl's headgroup, and therefore prevent amphiphiles from packing closely at interface. The results present a theoretical origin for useful application of KCGl in cosmetics, petroleum and daily chemical industries.


Assuntos
Compostos de Amônio/química , Glicina/química , Reologia , Tensão Superficial , Tensoativos/química , Cátions , Interações Hidrofóbicas e Hidrofílicas
7.
PLoS One ; 15(5): e0232846, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32380514

RESUMO

The structure of lactose permease, stabilized in a periplasmic open conformation by two Gly to Trp replacements (LacYww) and complexed with a nanobody directed against this conformation, provides the highest resolution structure of the symporter. The nanobody binds in a different manner than two other nanobodies made against the same mutant, which also bind to the same general region on the periplasmic side. This region of the protein may represent an immune hotspot. The CDR3 loop of the nanobody is held by hydrogen bonds in a conformation that partially blocks access to the substrate-binding site. As a result, kon and koff for galactoside binding to either LacY or the double mutant complexed with the nanobody are lower than for the other two LacY/nanobody complexes though the Kd values are similar, reflecting the fact that the nanobodies rigidify structures along the pathway. While the wild-type LacY/nanobody complex clearly stabilizes a similar 'extracellular open' conformation in solution, judged by binding kinetics, the complex with wild-type LacY did not yet crystallize, suggesting the nanobody does not bind strongly enough to shift the equilibrium to stabilize a periplasmic side-open conformation suitable for crystallization. However, the similarity of the galactoside binding kinetics for the nanobody-bound complexes with wild type LacY and with LacYWW indicates that they have similar structures, showing that the reported co-structures reliably show nanobody interactions with LacY.


Assuntos
Proteínas de Escherichia coli/química , Proteínas de Transporte de Monossacarídeos/química , Anticorpos de Domínio Único/química , Simportadores/química , Substituição de Aminoácidos , Reações Antígeno-Anticorpo , Sítios de Ligação , Cristalografia por Raios X , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/imunologia , Galactose/metabolismo , Glicina/química , Ligação de Hidrogênio , Cinética , Modelos Moleculares , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Transporte de Monossacarídeos/imunologia , Mutação de Sentido Incorreto , Mutação Puntual , Ligação Proteica , Conformação Proteica , Estabilidade Proteica , Anticorpos de Domínio Único/imunologia , Relação Estrutura-Atividade , Simportadores/genética , Simportadores/imunologia , Tiogalactosídeos/química , Triptofano/química
8.
PLoS Comput Biol ; 16(5): e1007904, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32453784

RESUMO

S-adenosylmethionine (SAM) is one of the most important enzyme substrates. It is vital for the function of various proteins, including large group of methyltransferases (MTs). Intriguingly, some bacterial and eukaryotic MTs, while catalysing the same reaction, possess significantly different topologies, with the former being a knotted one. Here, we conducted a comprehensive analysis of SAM conformational space and factors that affect its vastness. We investigated SAM in two forms: free in water (via NMR studies and explicit solvent simulations) and bound to proteins (based on all data available in the PDB and on all-atom molecular dynamics simulations in water). We identified structural descriptors-angles which show the major differences in SAM conformation between unknotted and knotted methyltransferases. Moreover, we report that this is caused mainly by a characteristic for knotted MTs compact binding site formed by the knot and the presence of adenine-binding loop. Additionally, we elucidate conformational restrictions imposed on SAM molecules by other protein groups in comparison to conformational space in water.


Assuntos
Sítios de Ligação , Metionina Adenosiltransferase/química , S-Adenosilmetionina/química , Adenina/química , Motivos de Aminoácidos , Biologia Computacional/métodos , Simulação por Computador , Bases de Dados de Proteínas , Glicina/química , Espectroscopia de Ressonância Magnética , Simulação de Dinâmica Molecular , Análise de Componente Principal , Ligação Proteica , Domínios Proteicos , Dobramento de Proteína , Solventes , Temperatura , Água/química , tRNA Metiltransferases/química
9.
J Environ Sci Health B ; 55(7): 646-654, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32432942

RESUMO

The aim of this work was to know the differential composition of the dissolved fraction of a glyphosate-based herbicide (GBH), commercialized as GLIFOPAC, when reaches different aquatic environments and its ecotoxicological effects on crustaceans species living in them. Daphnia magna, Tisbe longicornis, and Emerita analoga were exposed to glyphosate herbicide called GLIFOPAC (480 g L-1 of active ingredient or a.i.) at concentrations between 0.5 and 4.8 g a.i. L-1. Acute toxicity in D. magna (48 h-LC50), E. analoga (48 h-LC50), and T. longicornis (96 h-LC50) was studied. Chromatographic analysis of the GBH composition used and water (freshwater/sea water) polluted with GLIFOPAC were evaluated. Results reported acute toxicity (48-96 h-LC50) values for D. magna, E. analoga and T. longicornis of 27.4 mg L-1, 806.4 mg L-1, and 19.4 mg L-1, respectively. Chromatographic evaluation described around 45 substances of the GLIFOPAC composition, such as from the surfactant structures (aliphatic chain with esther/ether group), metabolites (AMPA), and other substances (glucofuranose, glucopyranoside, galactopyranose). This study evidenced differences in the GLIFOPAC composition in freshwater and marine water, which may differentiate the toxic response at the crustacean-level in each aquatic environment.


Assuntos
Crustáceos/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Braquiúros/efeitos dos fármacos , Ecotoxicologia/métodos , Biomarcadores Ambientais/efeitos dos fármacos , Água Doce , Glicina/química , Glicina/toxicidade , Herbicidas/química , Dose Letal Mediana , Testes de Toxicidade Aguda , Poluentes Químicos da Água/química
10.
J Phys Chem Lett ; 11(11): 4346-4352, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32401519

RESUMO

This work showcases cryogenic and temperature-dependent "iodide-tagging" photoelectron spectroscopy to probe specific binding sites of amino acids using the glycine-iodide complex (Gly·I-) as a case study. Multiple Gly·I- isomers were generated from ambient electrospray ionization and kinetically isolated in a cryogenic ion trap. These structures were characterized with temperature-dependent "iodide-tagging" negative ion photoelectron spectroscopy (NIPES), where iodide was used as the "messenger" to interpret electronic energetics and structural information of various Gly·I- isomers. Accompanied by theoretical computations and Franck-Condon simulations, a total of five cluster structures have been identified along with their various binding motifs. This work demonstrates that "iodide-tagging" NIPES is a powerful general means for probing specific binding interactions in biological molecules of interest.


Assuntos
Glicina/química , Iodetos/química , Espectroscopia Fotoeletrônica/métodos , Sítios de Ligação
11.
J Phys Chem A ; 124(20): 4150-4159, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32348131

RESUMO

The emergence of life on the prebiotic Earth must have involved the formation of polypeptides, yet the polymerization of amino acids is thermodynamically unfavorable under biologically relevant aqueous conditions because amino acids are zwitterions in solution and because of the production of a water molecule through a condensation reaction. Many mechanisms for overcoming this thermodynamic unfavorability have been proposed, but the role of gas phase water clusters has not been investigated. We present the thermodynamics of the water-mediated gas phase dimerization reaction of glycine as a model for the atmospheric polymerization of amino acids prior to the emergence of biological machinery. We hypothesize that atmospheric aerosols may have played a major role in the prebiotic formation of peptide bonds by providing the thermodynamic driving force to facilitate increasingly stable linear oligopeptides. In addition, we hypothesize that small aerosols orient amino acids on their surfaces, thus providing the correct molecular orientations to funnel the reaction pathways of peptides through transition states that lead eventually to polypeptide products. Using density functional theory and a thorough configurational sampling technique, we show that the thermodynamic spontaneity of the linear dimerization of glycine in the gas phase can be driven by the addition of individual water molecules.


Assuntos
Evolução Química , Gases/química , Origem da Vida , Peptídeos/química , Água/química , Sítios de Ligação , Dimerização , Glicina/química , Cinética , Modelos Moleculares , Prebióticos , Termodinâmica
12.
Eur J Med Chem ; 194: 112269, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32248002

RESUMO

RAS-RAF pathway presents a valuable target for the cancer treatment due to its important roles in the regulation of tumor proliferation, apoptosis and the obtained resistance. To explore such target a RAS/CRAF interference agent, was therefore conjugated with Pt(IV) prodrugs via ester bond, resulting in total eleven multifunctional Pt(IV) complexes. The complexes could target genomic DNA and disrupt the signaling transduction from RAS protein to CRAF so that block the mitogen-activated protein kinase (MAPK) signaling pathway. Experiments in vitro indicated that all of the Pt(IV) complexes showed potent anti-tumor activity with IC50 values ranged from 8 nM to 22.55 µM, which were significantly improved as compared with cisplatin (CDDP) whose IC50 values ranged from 5.45 µM to 9.05 µM. Among them, 26 exerted the best anti-tumor activity in vitro, which not only exhibited excellent cytotoxicity against normal tumor cells, but also against CDDP-resistance cell lines (e.g. A549/CDDP and SKOV-3/CDDP). Importantly, 26 only showed little effect on normal cell lines such as HUEVC and LO2. Besides, the following biological mechanisms studies demonstrated that 26 could efficiently enter. A549 cells, significantly arrest cell cycle at G2/M phase, disrupt the signaling pathway and trigger endogenous caspase apoptosis pathway. Furthermore, results of a xenograft subcutaneous model of A549 tumor showed that 26 could effectively decrease tumor growth rates without causing loss of bodyweight.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glicina/análogos & derivados , Compostos Organoplatínicos/farmacologia , Sulfonas/farmacologia , Quinases raf/antagonistas & inibidores , Proteínas ras/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cisplatino/farmacologia , Dano ao DNA , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glicina/química , Glicina/farmacologia , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Sulfonas/química , Quinases raf/metabolismo , Proteínas ras/metabolismo
13.
Proc Natl Acad Sci U S A ; 117(15): 8503-8514, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32234784

RESUMO

The specific interaction of importins with nuclear localization signals (NLSs) of cargo proteins not only mediates nuclear import but also, prevents their aberrant phase separation and stress granule recruitment in the cytoplasm. The importin Transportin-1 (TNPO1) plays a key role in the (patho-)physiology of both processes. Here, we report that both TNPO1 and Transportin-3 (TNPO3) recognize two nonclassical NLSs within the cold-inducible RNA-binding protein (CIRBP). Our biophysical investigations show that TNPO1 recognizes an arginine-glycine(-glycine) (RG/RGG)-rich region, whereas TNPO3 recognizes a region rich in arginine-serine-tyrosine (RSY) residues. These interactions regulate nuclear localization, phase separation, and stress granule recruitment of CIRBP in cells. The presence of both RG/RGG and RSY regions in numerous other RNA-binding proteins suggests that the interaction of TNPO1 and TNPO3 with these nonclassical NLSs may regulate the formation of membraneless organelles and subcellular localization of numerous proteins.


Assuntos
Núcleo Celular/metabolismo , Sinais de Localização Nuclear , Fragmentos de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , beta Carioferinas/metabolismo , Transporte Ativo do Núcleo Celular , Arginina/química , Arginina/metabolismo , Citoplasma/metabolismo , Glicina/química , Glicina/metabolismo , Células HeLa , Humanos , Fragmentos de Peptídeos/química , Ligação Proteica , Conformação Proteica , Proteínas de Ligação a RNA/química , Serina/química , Serina/metabolismo , Tirosina/química , Tirosina/metabolismo , beta Carioferinas/química
14.
Sci Rep ; 10(1): 3731, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111919

RESUMO

The alanine-serine-cysteine transporter Asc-1 regulates the synaptic availability of D-serine and glycine (the two co-agonists of the NMDA receptor) and is regarded as an important drug target. To shuttle the substrate from the extracellular space to the cytoplasm, this transporter undergoes multiple distinct conformational states. In this work, homology modeling, substrate docking and molecular dynamics simulations were carried out to learn more about the transition between the "outward-open" and "outward-open occluded" states. We identified a transition state involving the highly-conserved unwound TM6 region in which the Phe243 flips close to the D-serine substrate without major movements of TM6. This feature and those of other key residues are proposed to control the binding site and substrate translocation. Competitive inhibitors ACPP, LuAE00527 and SMLC were docked and their binding modes at the substrate binding site corroborated the key role played by Phe243 of TM6. For ACPP and LuAE00527, strong hydrophobic interactions with this residue hinder its mobility and prevent the uptake and the efflux of substrates. As for SMLC, the weaker interactions maintain the flexibility of Phe243 and the efflux process. Overall, we propose a molecular basis for the inhibition of substrate translocation of the Asc-1 transporter that should be valuable for rational drug design.


Assuntos
Sistema y+ de Transporte de Aminoácidos/química , Sistema y+ de Transporte de Aminoácidos/metabolismo , Motivos de Aminoácidos , Sistema y+ de Transporte de Aminoácidos/genética , Sítios de Ligação , Transporte Biológico , Glicina/química , Glicina/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Serina/química , Serina/metabolismo
15.
PLoS One ; 15(3): e0230022, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32143211

RESUMO

The objective of this study was to regulate the cytotoxicity of cisplatin (cisPt) minimizing its adverse effects. For this purpose, the lowest cisPt concentration needed to obtain a significant positive response in cutaneous squamous cell carcinoma (cSCC) was explored. Two adjuvant agents as gold nanoparticles (AuNP) and chelating tricine were tested as enhancers in cisPt treatment. Effectiveness of all treatments was assessed by means of biochemical techniques, which offer quantitative data, as well as two microscopy-based techniques that provided qualitative cell imaging. The present work confirms the effectiveness of free cisplatin at very low concentrations. In order to enhance its effectiveness while the side effects were probably diminished, cisPt 3.5 µM was administered with AuNP 2.5 mM, showing an effectiveness practically equal to that observed with free cisPt. However, the second treatment investigated, based on cisPt 3.5 µM combined with tricine 50 mM, enhanced drug effectiveness, increasing the percentage of cells dying by apoptosis. This treatment was even better in terms of cell damage than free cisPt at 15 µM. Images obtained by TEM and cryo-SXT confirmed these results, since a notable number of apoptotic bodies were detected when cisPt was combined with tricine. Thus, tricine was clearly a better adjuvant for cisPt treatments.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cisplatino/química , Portadores de Fármacos/química , Antineoplásicos/química , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Tamanho Celular/efeitos dos fármacos , Quelantes/química , Cisplatino/farmacologia , Glicina/análogos & derivados , Glicina/química , Glicina/toxicidade , Ouro/química , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Microscopia Eletrônica de Transmissão , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
16.
Chemistry ; 26(43): 9573-9579, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32216133

RESUMO

Peptoids, N-substituted glycine oligomers, represent an important class of peptidomimetics that can fold into three-dimensional structures in solution. Most of the folded peptoid structures, however, resemble helices, and this can limit their applications, specifically in asymmetric catalysis. In this work, for the first time, unique examples of pyrrolidine-based ß-turn-like peptoids are described and characterized, both in the solid state, by single-crystal X-ray analysis, and in solution, by circular dichroism spectroscopy. Furthermore, their highly efficient and enantioselective catalytic activity for the production of γ-nitro aldehydes by asymmetric Michael reaction in water was demonstrated. The structural properties and DFT-D3 calculations of the new ß-turn-like peptoids, as well as catalytic and spectroscopic studies on designed pyrrolidine-based helical peptoids, suggest that the ß-turn structure plays a key role in the stereoselectivity of the catalytic reaction.


Assuntos
Glicina/química , Peptidomiméticos/química , Peptoides/química , Catálise , Cristalografia por Raios X , Modelos Moleculares , Estereoisomerismo
17.
Chemistry ; 26(31): 7074-7082, 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32187746

RESUMO

The results of extended comparative investigation of nickel(II) Schiff base complexes (containing various auxiliary chiral moieties) commonly used as a methodological platform for the asymmetric synthesis of tailor-made α-amino acids are provided. The following issues are addressed: 1) redox activity (determining the possibility for electrochemically induced reactions); 2) quantitative estimation of the reactivity of deprotonated complexes towards electrophiles; and 3) quantum-chemical estimation of noncovalent interactions in the metal coordination environment (which shed light on the origin of the stereochemical outcome observed for different stereoinductors). Possible mechanisms that determine the relationship between the stereochemical configuration of a molecule and its electronic structure are discussed. The DFT-calculated HOMO-LUMO energies and localization, as well as relative energies for the (S)- and (R)-alanine derivatives, that determine the stereoinduction efficiency in thermodynamically controlled reactions in nickel(II) coordination are provided. The computational data are supported by experimental results on the monobenzylation of glycine derivatives.


Assuntos
Aminoácidos/química , Complexos de Coordenação/química , Bases de Schiff/química , Alanina/química , Glicina/química , Níquel/química , Estereoisomerismo , Termodinâmica
18.
Sci Adv ; 6(8): eaaz1955, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32128422

RESUMO

Selectively studying parts of proteins and metabolites in tissue with nuclear magnetic resonance promises new insights into molecular structures or diagnostic approaches. Nuclear spin singlet states allow the selection of signals from chemical moieties of interest in proteins or metabolites while suppressing background signal. This selection process is based on the electron-mediated coupling between two nuclear spins and their difference in resonance frequency. We introduce a generalized and versatile pulsed NMR experiment that allows populating singlet states on a broad scale of coupling patterns. This approach allowed us to filter signals from proton pairs in the Alzheimer's disease-related b-amyloid 40 peptide and in metabolites in brain matter. In particular, for glutamine/glutamate, we have discovered a long-lived state in tissue without the typically required singlet sustaining by radiofrequency irradiation. We believe that these findings will open up new opportunities to study metabolites with a view on future in vivo applications.


Assuntos
Espectroscopia de Ressonância Magnética , Peptídeos beta-Amiloides/química , Animais , Encéfalo/metabolismo , Glicina/química , Metaboloma , Ratos Wistar , Processamento de Sinais Assistido por Computador
19.
Macromol Rapid Commun ; 41(6): e1900583, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32009279

RESUMO

A unique cuboid spider silk from the outer egg sac of Nephila pilipes, with an unusual square cross-section, is disclosed. The structure-function relationships within this silk are first studied through structural characterization, mechanical measurement, protein conformation, and polypeptide signature of silk proteins. This silk maintains the higher stiffness property of egg sac silks, and also shows a species difference. Environmental response of the mechanical properties within this silk are observed. Synchrotron FTIR microspectroscopy is used to monitor the silk protein conformation in a single natural silk. The ß-sheet structure aligns parallel to the fiber axis with a content of 22% ± 2.6%. The de novo resulting polypeptide from the solid silk fibers are novel, and an abundant polar amino acid insertion is observed. Short polyalanine (An , n ≤ 3), alternating serine and alanine (S/A)X, and alternating glycine and alanine (G/A)X, GGX, and SSX dominates in the resulting de novo polypeptide. This accords with the composition pattern of other egg sac silk proteins, besides the rarely observed GGX. This study broadens the library of egg sac spider silks and provides a new perspective to uncover structure-function relationships in spider silk.


Assuntos
Aminoácidos/química , Fibroínas/química , Peptídeos/química , Seda/química , Alanina/química , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Fibroínas/ultraestrutura , Glicina/química , Teste de Materiais , Conformação Proteica em Folha beta , Serina/química , Seda/ultraestrutura , Aranhas/química , Relação Estrutura-Atividade
20.
ACS Appl Mater Interfaces ; 12(8): 9008-9016, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32011853

RESUMO

This paper presents flexible pressure sensors based on free-standing and biodegradable glycine-chitosan piezoelectric films. Fabricated by the self-assembly of biological molecules of glycine within a water-based chitosan solution, the piezoelectric films consist of a stable spherulite structure of ß-glycine (size varying from a few millimeters to 1 cm) embedded in an amorphous chitosan polymer. The polymorphic phase of glycine crystals in chitosan, evaluated by X-ray diffraction, confirms formation of a pure ferroelectric phase of glycine (ß-phase). Our results show that a simple solvent-casting method can be used to prepare a biodegradable ß-glycine/chitosan-based piezoelectric film with sensitivity (∼2.82 ± 0.2 mV kPa-1) comparable to those of nondegradable commercial piezoelectric materials. The measured capacitance of the ß-glycine/chitosan film is in the range from 0.26 to 0.12 nF at a frequency range from 100 Hz to 1 MHz, and its dielectric constant and loss factor are 7.7 and 0.18, respectively, in the high impedance range under ambient conditions. The results suggest that the glycine-chitosan composite is a promising new biobased piezoelectric material for biodegradable sensors for applications in wearable biomedical diagnostics.


Assuntos
Plásticos Biodegradáveis , Quitosana/química , Glicina/química , Pressão
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