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1.
Biosci Biotechnol Biochem ; 84(1): 37-42, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31578944

RESUMO

The monoterpene, trans-p-menth-3-ene-1,2,8-triol, is a naturally occurring alcohol isolated from several herbal plants. In the present work, the asymmetric synthesis of both enantiomers of this natural product was achieved using Sharpless asymmetric dihydroxylation as the key step. A reversal of enantiofacial selectivity was observed in the asymmetric dihydroxylation.


Assuntos
/química , Extratos Vegetais/química , Extratos Vegetais/síntese química , Cromatografia em Gel , Cristalização , Cromatografia Gasosa-Espectrometria de Massas , Hidrogenação , Hidroxilação , Isomerismo , Conformação Molecular , Extratos Vegetais/isolamento & purificação , Sílica Gel
2.
Food Chem ; 305: 125481, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31525592

RESUMO

Prebiotics are rising in interest in commercial scale productions due to increasing health awareness of consumers. Under bio-economic aspects, sweet and acid whey provide a suitable feed medium for the enzymatic generation of prebiotic lactulose. Since whey has a broad variation in composition, the influence of the feed composition on the concentration of generated lactulose was investigated. The influence of lactose and fructose concentration as well as enzymatic activity of two commercially available ß-galactosidases were investigated. The results were evaluated via response surface analysis with a quadratic model containing pairwise interaction terms. The optimal feed composition yielding a theoretical maximal amount of lactulose was determined as 1.28 or 0.74 mol/kg fructose and 0.17 or 0.19 mol/kg lactose with an enzymatic activity of 2.0 or 2.8 µkat/kg for acid (pH 4.4) or sweet (pH 6.6) whey. Furthermore, the major reaction product was isolated and subsequently, the structural identity was elucidated and verified via extensive NMR analysis.


Assuntos
Lactulose/metabolismo , Soro do Leite/metabolismo , beta-Galactosidase/metabolismo , Frutose/metabolismo , Concentração de Íons de Hidrogênio , Isomerismo , Lactose/metabolismo , Lactulose/isolamento & purificação , Espectroscopia de Ressonância Magnética , Soro do Leite/química
3.
J Sci Food Agric ; 100(1): 343-353, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31584698

RESUMO

BACKGROUND: Herbs are rich in various beneficial bioactive compounds and they can be used for many different purposes. One of the most common is maceration of herbs in alcohol. Different substances respond differently to extraction in prepared solutions. It is very important to enhance the highest proportion of beneficial ingredients during the maceration process in a herbal liqueur. A comparative analysis of numerous different phenolic compounds from eight of the most frequently used herbs for making aperitifs in Europe was performed. RESULTS: In the comparison among all studied herbs, the highest phenolic content was found with Artemisia absinthium (wormwood) (14.61 mg g-1 ) and Mentha piperita (peppermint) (13.89 mg g-1 ), while the lowest content was found with Centaurium erythraea (common centaury) (3.96 mg g-1 ). Salvianolic acid isomers and caffeic acid derivatives were the greatest contributors to the total phenolic content in lemon balm, wormwood, peppermint, fennel and sage. These compounds contain more hydroxyl groups and they were better extracted at the beginning of the maceration process. Caraway and common centaury contain more flavonols (quercetin and kaempferol derivatives), with higher chemical stability and fewer hydroxyl groups in their structure. CONCLUSION: The compositions of eight herbal liqueurs were highly related to the presence of different herbal ingredients and their solubility in the extract over time. Most flavonol derivatives were extracted over a longer time and the two liqueurs (common centaury and caraway) therefore had the highest phenolic contents after 3 weeks of maceration. © 2019 Society of Chemical Industry.


Assuntos
Bebidas Alcoólicas/análise , Extratos Vegetais/química , Plantas Medicinais/química , Artemisia/química , Carum/química , Centaurium/química , Europa (Continente) , Manipulação de Alimentos , Isomerismo , Mentha piperita/química , Fenóis/química
4.
J Agric Food Chem ; 67(46): 12863-12874, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31670949

RESUMO

A comprehensive quantitative characterization of Maillard reaction products was carried out for conventional (CON) and lactose-hydrolyzed (LH) ultrahigh temperature (UHT) milk during storage at 20, 30, and 40 °C for 1 year. The accumulation of 3-deoxyglucosone (3-DG) and 3-deoxygalactosone (3-DGal) in LH-UHT milk ranged from 20-fold (at 20 °C) to 44-fold (at 40 °C) higher than that in CON-UHT milk. High temperature storage (40 °C) significantly accelerated the accumulation of 3-DG, 3-DGal, and 5-hydroxymethyl furfural but not the majority of the analyzed advanced glycation endproducts (AGEs). The concentrations of major AGEs including N-ε-carboxymethyllysine (CML), N-ε-carboxyethyllysine (CEL), methylglyoxal-hydroimidazolone isomers (MG-H1/H3), glyoxal-hydroimidazolone isomers (G-H1/H3), and G-H2 detected in CON milk during storage were in the range 12-700, 1-14, 8-45, 4-13, and 1-30 µM, respectively, while they were 30-570, 2-88, 17-150, 9-20, and 5-34 µM, respectively, in LH milk. Pyrraline, S-(carboxymethyl)cysteine (CMC), and glyoxal-lysine dimer were detected in lower levels, while MG-H2, methylglyoxal-lysine dimer, argpyrimidine, glyoxal-lysine-amide, glycolic acid-lysine-amide, and pentosidine were not detected in any of the milk samples. This work demonstrates for the first time that five of the analyzed AGEs (CML, CEL, MG-H1/H3, G-H1/H3, and G-H2) could be selected as markers for evaluation of the extent of the Maillard reaction in UHT milk. These results contribute to a better understanding of how Maillard reactions progress during storage of UHT milk and can be used to develop strategies to inhibit Maillard reactions in LH milk.


Assuntos
Produtos Finais de Glicação Avançada/análise , Lactose/química , Leite/química , Animais , Bovinos , Desoxiglucose/análogos & derivados , Desoxiglucose/análise , Armazenamento de Alimentos , Galactose/análogos & derivados , Galactose/análise , Isomerismo , Lisina/análogos & derivados , Lisina/análise , Reação de Maillard , Aldeído Pirúvico/análise , Temperatura Ambiente
5.
Chem Soc Rev ; 48(23): 5596-5615, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31675020

RESUMO

A number of self-sufficient hydride transfer processes have been reported in biocatalysis, with a common feature being the dependence on nicotinamide as a cofactor. This cofactor is provided in catalytic amounts and serves as a hydride shuttle to connect two or more enzymatic redox events, usually ensuring overall redox neutrality. Creative systems were designed to produce synthetic sequences characterized by high hydride economy, typically going in hand with excellent atom economy. Several redox enzymes have been successfully combined in one-pot one-step to allow functionalization of a large variety of molecules while preventing by-product formation. This review analyzes and classifies the various strategies, with a strong focus on efficiency, which is evaluated here in terms of the hydride economy and measured by the turnover number of the nicotinamide cofactor(s). The review ends with a critical evaluation of the reported systems and highlights areas where further improvements might be desirable.


Assuntos
Enzimas/metabolismo , NAD/metabolismo , Biocatálise , Enzimas/química , Isomerismo , NAD/química , Oxirredução , Especificidade por Substrato
6.
Phys Chem Chem Phys ; 21(46): 25728-25734, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31720623

RESUMO

Proteorhodopsin (PR) is a proton-pumping rhodopsin, and it is known to exhibit a multi-phasic decay of the excited-state population in the primary process. So far, this complex excited-state decay has been attributed to the branching of the relaxation pathway on the excited-state potential energy surface. However, a recent ultrafast spectroscopic study on a sodium-pumping rhodopsin suggested that such a complex decay may originate from the heterogeneity in the ground state due to the acid-base equilibrium of the counterion of the protonated retinal Schiff base (PRSB). In this study, we studied the excited-state dynamics of PR at pH 11 and 4, in which the counterion of the PRSB, Asp97, is completely deprotonated and protonated, respectively. The obtained time-resolved absorption data revealed that the excited-state lifetime is decisively governed by the protonation state of Asp97, and the photoisomerization of the PRSB chromophore proceeds faster and more efficiently when Asp97 is deprotonated. This conclusion was further supported by high similarity of the excited-state dynamics between PR at pH 4 and the D97N mutant in which Asp97 is replaced with neutral Asn. The results of this study suggest that the protonation state of the PRSB counterion plays a decisive role in determining the excited-state dynamics and the photoisomerization reactivity of rhodopsins in general, by making a significant influence on the exited-state potential energy surface of the PRSB chromophore.


Assuntos
Isomerismo , Rodopsinas Microbianas/química , Concentração de Íons de Hidrogênio , Processos Fotoquímicos , Teoria Quântica
7.
Phys Chem Chem Phys ; 21(41): 22857-22868, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31599896

RESUMO

Three low-energy isomers of 9-methylguanine, the amino-oxo (AO) form and two amino-hydroxy (AH1 and AH2) conformers, were trapped from the gas phase into low-temperature argon matrices. The AH1 and AH2 isomers, differing in the orientation of the OH group, were found to transform into each other upon excitation with near-IR light. The population of the AO form of the compound was not changed upon any near-IR irradiation of the matrix samples. Using monochromatic near-IR light, generated by a frequency-tunable laser source, it was possible to selectively induce the AH1 → AH2 or AH2 → AH1 conversion. Photoreversibility of this conformational transformation was then demonstrated. Exposure of matrix-isolated monomers of 9-methylguanine to broadband near-IR light also led to conformational conversions within the amino-hydroxy tautomeric form; the final stage of this process was always the same photostationary state independent of the initial ratio of AH1 and AH2 populations. Spontaneous conformational conversion, transforming the higher-energy AH2 form into the lower-energy AH1 isomer, was observed for matrix-isolated monomers of 9-methylguanine kept in the dark. The mechanism of this process must rely on quantum tunneling of the light hydrogen atom. Irradiation of matrix-isolated 9-methylguanine with UV laser light at λ = 288 or 285 nm led to a substantial consumption of the two AH forms, while the amount of AO isomer remained unchanged. On the other hand, a decrease in the population of the AO isomer occurred upon excitations at shorter wavelengths, λ = 280 or 275 nm. The spectral changes observed after UV-irradiation suggest the generation (and stabilization in the matrix) of a radical species, resulting from the photocleavage of the O-H or N1-H bonds, in the AH or AO isomer, respectively.


Assuntos
Argônio/química , Temperatura Baixa , Guanina/análogos & derivados , Raios Infravermelhos , Raios Ultravioleta , Guanina/química , Isomerismo , Conformação Molecular/efeitos da radiação
8.
J Agric Food Chem ; 67(42): 11752-11757, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31554403

RESUMO

Resveratrol (3,5,4'-trihydroxystilbene) is one of the most abundant polyphenols in red grapes, and red wine represents one of the most important dietary sources of this compound. Although its beneficial properties on human health have been widely investigated over the last 30 years, very little is known about its derivatives. Resveratrol can indeed undergo glycosylation, oligomerization and, upon UV-light exposure, it can isomerize from the trans-to the cis-isomer, which can further cyclize to 2,4,6-trihydroxyphenanthrene (THP). Although the effects of THP on human health are not yet known, being a polycyclic aromatic hydrocarbon, it can be potentially harmful. Because no data about THP occurrence in plant food and beverages are available, a simple procedure based on liquid-liquid extraction and gas chromatography-mass spectrometry has been developed and validated for the simultaneous qualitative and quantitative analysis of trans-resveratrol, cis-resveratrol, and THP in red wine, before and after UV-light exposure.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Fenantrenos/química , Resveratrol/química , Vinho/análise , Vinho/efeitos da radiação , Glicosilação , Isomerismo , Raios Ultravioleta
9.
J Agric Food Chem ; 67(40): 11210-11218, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31512471

RESUMO

The aim of this work was to provide recent fatty acid (FA) profiling of chocolates and chocolate products, principally C18:1 trans FAs (TFAs). Thirty-two samples were analyzed by gas chromatography and FAs were quantified. The total TFA content declared in chocolate labeling and the real TFA content were compared. The TFA content ranged from 0.04 to 2.51 g/100 g of sample, and it was noticed that several manufacturers were underestimating the total TFA content in their labeling. The main TFA isomers quantified were C18:1 trans-9 (0.006-0.244%), C18:1 trans-10 (0.009-0.392%), and C18:1 trans-11 (0.013-0.464%), expressed in g/100 g of sample. Principal component analysis was used to discriminate industrial fats from natural trans fats based on the isomeric TFA profile and dairy fat (DF) biomarkers allowing to group samples in four clusters: high TFA content and high DF content, high TFA content and low DF content, low TFA content and high DF content, and low TFA content and low DF content.


Assuntos
Chocolate/análise , Lipídeos/química , Ácidos Graxos Trans/química , Brasil , Rotulagem de Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Isomerismo
10.
Chem Pharm Bull (Tokyo) ; 67(9): 1000-1005, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474722

RESUMO

α,ß-Unsaturated carbonyl compounds readily form adducts with SH or NH2 residues, which are nucleophilic agents, by Michael addition. Glutathione (GSH) is a tripeptide that contains an SH residue and functions as an antioxidant. We demonstrated previously that acrolein (ACR), crotonaldehyde (CA), and methyl vinyl ketone (MVK) are present in nicotine- and tar-removed cigarette smoke extract (CSE) and reacted with GSH in B16-BL6 mouse melanoma cells to form GSH-ACR, GSH-CA, and GSH-MVK adducts, suggesting a possible mechanism for CSE-induced cytotoxicity. In this study, we searched for novel α,ß-unsaturated carbonyl compounds other than ACR, CA, and MVK. We selected candidate compounds in CSE based on accurate mass values generated using LC/MS analysis of products formed between CSE and GSH, and identified these using GC/MS analysis and library screening. As a result, we isolated trans-2-methyl-2-butenal, 2-methyl-2-cyclopenten-1-one, 3-methyl-2-cyclopenten-1-one, and furfural, which were poorly reactive with GSH and only very weakly inhibited growth of Colon-26 mouse carcinoma cells and BALB/3T3 clone A31 mouse normal cells. We also isolated 2-cyclopenten-1-one, trans-2-pentenal, 3-methyl-2-butenal and ethyl vinyl ketone, which were highly reactive with GSH and significantly inhibited the growth of both cell lines. Our data suggest that the reactivity of compounds in CSE with GSH may be positively correlated with the effect on inhibiting cell growth. Notably, trans-2-pentenal showed marked inhibition of carcinoma cells growth, whereas this compound exhibited little inhibitory effect on normal cells. trans-2-Pentenal may be a potent candidate or seed for antitumor agents.


Assuntos
Aldeídos/química , Glutationa/química , Fumaça/análise , Aldeídos/toxicidade , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Isomerismo , Espectrometria de Massas , Camundongos
11.
J Agric Food Chem ; 67(35): 9916-9925, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31398025

RESUMO

Targeted analysis confirmed the presence of new phytosterol degradation products in fully hydrogenated commercial samples. EI-MS, APCI-MS, and 1D-NMR experiments led to the identification of 10 novel markers of catalytic hydrogenation, among which 5α-sitostan-3-one and 5α-campestan-3-one, isomers of saturated and monounsaturated steroidal hydrocarbons, were reported in edible oils for the first time. Examination of the phytosterol degradation mechanism was done by the catalytic transfer deuteration technique. The mitigation strategy of potentially detrimental compounds included optimization of processing parameters. The effect of catalyst dosage (≤0.1% based on Ni basis) and temperature region (>180 °C) were the most crucial factors in phytosterol degradation control.


Assuntos
Hidrocarbonetos/química , Óleos Vegetais/química , Catálise , Temperatura Alta , Hidrogenação , Isomerismo , Espectroscopia de Ressonância Magnética , Fitosteróis/química , Espectrometria de Massas por Ionização por Electrospray
12.
J Cosmet Sci ; 70(3): 137-147, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31398102

RESUMO

The antimicrobial properties of natural limonene and the compounds obtained after isomerization of limonene (α-terpinene, γ-terpinene, terpinolene, and p-cymene) were studied. The following microorganisms were selected for the tests: Gram-negative bacteria Escherichia coli K12 (ACCT 25922), Gram-positive Staphylococcus epidermidis (ACCT 49461), yeast fungi Candida albicans, and fungi Trichophyton rubrum, Aspergillus niger, Penicillium commune, Trichoderma viride, and Cladosporium cladosporioides. During the studies, terpinolene showed the highest activity, and therefore, this compound was chosen for the preparation of therapeutic creams (content of terpinolene: 0.5 and 2 wt%). The obtained creams were active in the microbiological tests even at the lowest content of terpinolene. The mixture of products obtained after the isomerization of limonene also showed antimicrobial activity. Probably, in the future, this mixture of products can be used as a potential and relatively inexpensive ingredient in therapeutic and protective creams that can be applied for the relief of skin lesions and in the treatment of acne or atopic dermatitis.


Assuntos
Limoneno/química , Catálise , Isomerismo , Monoterpenos , Dióxido de Silício , Terpenos
13.
Forensic Sci Int ; 302: 109900, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31382222

RESUMO

Currently, forensic drug experts are facing chemical identification challenges with the increasing number of new isomeric forms of psychoactive substances occurring in case samples. Very similar mass spectra for these substances could easily result in misidentification using the regular GC-MS screening methods in combination with colorimetric testing in forensic laboratories. Building on recent work from other groups, this study demonstrates that GC-VUV is a powerful technique for drug isomer differentiation, showing reproducible and discriminating spectra for aromatic ring-isomers. MS and VUV show complementary selectivity as VUV spectra are ring-position specific whereas MS spectra are characteristic for the amine moieties of the molecule. VUV spectra are very reproducible showing less than 0.1‰ deviation in library match scores and therefore small spectral differences suffice to confidently distinguish isomers. In comparison, MS match scores gave over 10‰ deviation and showed significant overlap in match score ranges for several isomers. This poses a risk for false positive identifications when assigning compounds based on retention time and GC-MS mass spectrum. A strategy was developed, based on Kernel Density Estimations of match scores, to construct Receiver Operating Characteristic (ROC) curves and estimate likelihood ratios (LR values) with respect to the chemical differentiation of drug related isomers. This approach, and the added value of GC-VUV is demonstrated with the chemical analysis of several samples from drug case work from the Amsterdam area involving both compounds listed in Dutch drug legislation (3,4-MDMA; 3,4-MDA; 4-MMC; 4-MEC and 4-FA) as well as their unlisted and thus uncontrolled isomers (2,3-MDMA; 2,3-MDA; 2- and 3-MMC; 2- and 3-MEC and 2- and 3-FA).


Assuntos
Cromatografia Gasosa/métodos , Isomerismo , Espectrofotometria Ultravioleta/métodos , Medicamentos Sintéticos/química , Vácuo , Cromatografia Gasosa-Espectrometria de Massas
14.
J Mass Spectrom ; 54(9): 738-749, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31368246

RESUMO

Black pepper, though commonly employed as a spice, has many medicinal properties. It consists of volatile oils, alkaloids, pungent resins, etc., of which piperine is a major constituent. Though safe at low doses, piperine causes alteration in the activity of drug metabolising enzymes and transporters at high dose and is known to precipitate liver toxicity. It has a potential to form reactive metabolite(s) (RM) owing to the presence of structural alerts, such as methylenedioxyphenyl (MDP), α, ß-unsaturated carbonyl group (Michael acceptor), and piperidine. The present study was designed to detect and characterize stable and RM(s) of piperine formed on in vitro incubation with human liver microsomes. The investigation of RMs was done with the aid of trapping agents, viz, glutathione (GSH) and N-acetylcysteine (NAC). The samples were analysed by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS) using Thermo Scientific Q Exactive Plus Orbitrap. Full scan MS followed by data-dependent MS2 (Full MS-ddMS2 ) mode was used to establish mass spectrometric fragmentation pathways of protonated piperine and its metabolites. In total, four stable metabolites and their isomers (M1a-c, M2a-b, M3a-c, and M4a-b) were detected. Their formation involved removal of carbon (3, M1a-c), hydroxylation (2, M2a-b), hydroxylation with hydrogenation (3, M3a-c), and dehydrogenation (2, M4a-b). Out of these metabolites, M1, M2, and M3 are reported earlier in the literature, but their isomers and two M4 variants are novel. In addition, six novel conjugates of RMs, including three GSH conjugates of m/z 579 and three NAC conjugates of m/z 435, were also observed.


Assuntos
Alcaloides/análise , Alcaloides/metabolismo , Benzodioxóis/análise , Benzodioxóis/metabolismo , Microssomos Hepáticos/metabolismo , Piperidinas/análise , Piperidinas/metabolismo , Alcamidas Poli-Insaturadas/análise , Alcamidas Poli-Insaturadas/metabolismo , Acetilcisteína/química , Cromatografia Líquida de Alta Pressão , Glutationa/química , Humanos , Isomerismo , Espectrometria de Massas em Tandem
15.
Phytochemistry ; 166: 112077, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31374519

RESUMO

Radical scavenging activity and subsequent oxidation resulting in quinone products represent one of the important features of phenols occurring in plants and other biological systems. However, corresponding thermochemistry data can be still considered scarce. For phenol and 25 para-substituted phenols, we investigate the thermodynamics of the individual reaction steps, including three subsequent hydrogen atom transfers, as well as hydroxyl HO radical addition, leading to final ortho-quinone formation. The substituent and solvent effect of water on corresponding reactions enthalpies is elucidated. Solvent enhances substituent induced changes in the investigated reaction enthalpies. The reliability of employed computational methods for the thermodynamics of hydrogen atom donating ability of studied phenols and catechols is assessed, too. Obtained linear equations enable estimation of studied reaction enthalpies from Hammett constants of substituents.


Assuntos
Depuradores de Radicais Livres/química , Fenóis/química , Quinonas/química , Radical Hidroxila/química , Isomerismo , Relação Estrutura-Atividade , Termodinâmica
16.
Phys Chem Chem Phys ; 21(35): 19480-19487, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31461090

RESUMO

The deoxygenation reaction of m-benzenediol (resorcinol), an important lignin model compound, was studied in a hot microreactor. We revealed three decomposition channels by detecting elusive and reactive intermediates and product isomers selectively and found that resorcinol, similarly to catechol (o-benzenediol) and hydroquinone (p-benzenediol), (i) gets decarbonylated to yield hydroxycyclopentadiene. Additionally, (ii) decarboxylation (CO2 loss) yields C5H6 species in a retro-Diels-Alder reaction from a lactone species. Only acyclic products are detected at lower reactor temperatures and the most stable C5H6 isomer, cyclopentadiene (c-C5H6), is only observed at higher temperatures. Finally, (iii) two reactive ketene species, ethenone and buta-1,3-dienal, were observed in a third reaction channel. Both decarboxylation and ketene formation channels are unique among benzenediols for the meta-isomer, resorcinol. We have explored the resorcinol potential energy surface to rationalize the observed reactions. These findings may help to understand the source of ketenes in catalytic lignin depolymerization and give new insight into isomer-specific deoxygenation processes.


Assuntos
Dióxido de Carbono/síntese química , Etilenos/síntese química , Cetonas/síntese química , Resorcinóis/química , Reação de Cicloadição , Isomerismo , Oxigênio/química , Temperatura Ambiente
17.
Chem Commun (Camb) ; 55(69): 10192-10213, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31411602

RESUMO

Light is unsurpassed in its ability to modulate biological interactions. Since their discovery, chemists have been fascinated by photosensitive molecules capable of switching between isomeric forms, known as photoswitches. Photoswitchable peptides have been recognized for many years; however, their functional implementation in biological systems has only recently been achieved. Peptides are now acknowledged as excellent protein-protein interaction modulators and have been important in the emergence of photopharmacology. In this review, we briefly explain the different classes of photoswitches and summarize structural studies when they are incorporated into peptides. Importantly, we provide a detailed overview of the rapidly increasing number of examples, where biological modulation is driven by the structural changes. Furthermore, we discuss some of the remaining challenges faced in this field. These exciting proof-of-principle studies highlight the tremendous potential of photocontrollable peptides as optochemical tools for chemical biology and biomedicine.


Assuntos
Descoberta de Drogas , Peptídeos/química , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Morte Celular/efeitos dos fármacos , Descoberta de Drogas/métodos , Humanos , Isomerismo , Luz , Modelos Moleculares , Ácidos Nucleicos/metabolismo , Peptídeos/metabolismo , Processos Fotoquímicos , Mapas de Interação de Proteínas/efeitos dos fármacos
18.
Phys Chem Chem Phys ; 21(32): 17893-17900, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31380529

RESUMO

The dispersion interaction was reported to play a critical role in the stabilization of model dipeptide Z-Arg-OH, even greater than the conventional hydrogen bond (HB), which is opposite to the traditional opinion. Here the conformation of Z-Arg-OH has been systematically searched by the effective fragment based step-by-step strategy. All the newly-found low-energy conformers determined at the advanced DSD-PBEP86-D3(BJ)/aug-cc-pVTZ level are clearly in the stretched form with strong conventional HBs, rather than the reported folded structures with emphasis on the dispersion interactions. The simulated IR spectra of the stretched conformers fit better than those of the folded ones compared with the previous experimental observations. Near-edge X-ray absorption fine-structure (NEXAFS) spectra and X-ray photoelectron spectra (XPS) at C, N and O K-edges have also been simulated to unambiguously identify different isomers. This work thus provides valuable insight into the competitions between the conventional HB and the dispersion interactions and demonstrates that the conventional hydrogen bonding is still more important for such small peptides.


Assuntos
Arginina/análogos & derivados , Arginina/química , Dipeptídeos/química , Modelos Moleculares , Ligações de Hidrogênio , Isomerismo , Fenômenos Físicos , Conformação Proteica , Estabilidade Proteica , Solventes/química , Termodinâmica
19.
Nat Methods ; 16(8): 703-706, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31363206

RESUMO

Proteins can be phosphorylated at neighboring sites resulting in different functional states, and studying the regulation of these sites has been challenging. Here we present Thesaurus, a search engine that detects and quantifies phosphopeptide positional isomers from parallel reaction monitoring and data-independent acquisition mass spectrometry experiments. We apply Thesaurus to analyze phosphorylation events in the PI3K/AKT signaling pathway and show neighboring sites with distinct regulation.


Assuntos
Fosfopeptídeos/análise , Fosfoproteínas/análise , Proteoma/análise , Ferramenta de Busca/métodos , Células HeLa , Humanos , Proteínas Substratos do Receptor de Insulina/metabolismo , Isomerismo , Células MCF-7 , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Espectrometria de Massas em Tandem
20.
Adv Exp Med Biol ; 1140: 299-316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347055

RESUMO

The pharmaceutical and clinical industries are imperative for the maintenance of global health and welfare and require accurate, reproducible, and high throughput analyses. Technological advancements, such as the development and implementation of liquid chromatography-tandem mass spectrometry (LC-MS), have allowed for improvements in these areas, however there is still room for development. One way in which current analyses may be improved is by the implementation of ion mobility technology. Ion mobility has the capability to produce much more comprehensive data sets, by providing separation of isomers, as well as improving throughput, with separations being performed as fast as 60 ms. Here we will discuss the potential for ion mobility to assist in the two specific areas of glycosylation monitoring of biological drugs, and vitamin D analysis, as representatives of ion mobility's potential in both the pharmaceutical and clinical industries, respectively, as well as the current hurdles of ion mobility adoption in both fields.


Assuntos
Química Farmacêutica/métodos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Glicosilação , Isomerismo , Preparações Farmacêuticas/análise , Vitamina D/análise
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