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Anthocyanins are a class of compounds potentially used as food dyes. Thus, this study aimed to obtain and characterize natural extracts from Melinis minutiflora inflorescence (M), Plinia. cauliflora peel (JP) and P. cauliflora peel and seeds (JPS) and apply them as natural food dyes in gelatins. The extracts did not show statistically significant differences in pH values and water activity. The M and JPS extracts showed similar values of anthocyanins and total phenolic compounds and were higher than those from the JP extract. The M and JPS extracts showed a bathochromic effect, which was not observed for the JP extract. The bathochromic effect may indicate a possible complexation of anthocyanins. The color composition analysis revealed that the JP extract has a higher absorbance at a wavelength of 520 nm, indirectly suggesting the presence of more monomeric anthocyanins in its composition. The extract application test in gelatin did not change the texture properties of the gelatins. In addition, our findings revealed that the JPS extract had the best color stability after ten days of analysis, indicating that anthocyanin complexation with the phenolic compounds of P. cauliflora seeds contributed more effectively to anthocyanin stability in the model used.
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Antocianinas , Polifenóis , Antocianinas/análise , Polifenóis/análise , Gelatina , Frutas/química , Inflorescência/química , Fenóis/análise , Poaceae , Corantes/análise , Extratos Vegetais/químicaRESUMO
Despite their limitations, the pharmacokinetics (PK) and pharmacodynamics (PD) indices form the basis for our current understanding regarding antibiotic development, selection, and dose optimization. Application of PK-PD in medicine has been associated with better clinical outcome, suppression of resistance, and optimization of antibiotic consumption. Beta-lactam antibiotics remain the cornerstone for empirical and directed therapy in many patients. The percentage of time of the dosing interval that the free (unbound) drug concentration remains above the minimal inhibitory concentration (MIC) (%fT > MIC) has been considered the PK-PD index that best predicts the relationship between antibiotic exposure and killing for the beta-lactam antibiotics. Time dependence of beta-lactam antibiotics has its origin in the acylation process of the serine active site of penicillin-binding proteins, which subsequently results in bacteriostatic and bactericidal effects during the dosing interval. To enhance the likelihood of target attainment, higher doses, and prolonged infusion strategies, with/or without loading doses, have been applied to compensate for subtherapeutic levels of antibiotics related to PK-PD changes, especially in the early phase of severe sepsis. To minimize resistance and maximize clinical outcome, empirical therapy with a meropenem loading dose followed by high-dose-prolonged infusion should be considered in patients with high inoculum infections presenting as severe (Gram negative) sepsis. Subsequent de-escalation and dosing of beta-lactam antibiotics should be considered as an individualized dynamic process that requires dose adjustments throughout the time course of the disease process mediated by clinical parameters that indirectly assess PK-PD alterations.
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Anthocyanins (ANCs) are naturally occurring water-soluble pigments responsible for conferring red, blue, and purple colors to fruits, vegetables, flowers, and grains. Due to their chemical structure, they are highly susceptible to degradation by external factors, such as pH, light, temperature, and oxygen. Naturally acylated anthocyanins have proven to be more stable in response to external factors and exhibit superior biological effects as compared with their non-acylated analogues. Therefore, synthetic acylation represents a viable alternative to make the application of these compounds more suitable for use. Enzyme-mediated synthetic acylation produces derivatives that are highly similar to those obtained through the natural acylation process, with the main difference between these two pathways being the catalytic site of the enzymes involved in the synthesis; acyltransferases catalyze natural acylation, while lipases catalyze synthetic acylation. In both cases, their active sites perform the addition of carbon chains to the hydroxyl groups of anthocyanin glycosyl moieties. Currently, there is no comparative information regarding natural and enzymatically acylated anthocyanins. In this sense, the aim of this review is to compare natural and enzyme-mediated synthetic acylated anthocyanins in terms of chemical stability and pharmacological activity with a focus on inflammation and diabetes.
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Metabolic syndrome is a complex disorder that combines abdominal obesity, dyslipidemia, hypertension, and insulin resistance. Metabolic syndrome affects 25% of the world's population. Agave fructans have shown positive effects on alterations related to metabolic syndrome, so some investigations have focused on their bioconjugation with fatty acids to increase their biological activity. The objective of this work was to evaluate the effect of agave fructan bioconjugates in a rat model with metabolic syndrome. Agave fructans enzymatically bioconjugated (acylated via food-grade lipase catalysis) with propionate or laurate were administered orally for 8 weeks in rats fed a hypercaloric diet. Animals without treatment were used as the control group, as well as animals fed with a standard diet. The data indicate that the group of animals treated with laurate bioconjugates showed a significant decrease in glucose levels, systolic pressure, weight gain, and visceral adipose tissue, as well as a positive effect of pancreatic lipase inhibition. These results allow us to demonstrate the potential of agave bioconjugates, particularly laurate bioconjugates, for the prevention of diseases associated with metabolic syndrome.
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AIMS: Since plasma ghrelin can undergo des-acylation and proteolysis, the aim of this study was to investigate the extent to which an enhancement of these reactions is associated to the decrease of ghrelin in plasma after food intake or in individuals with obesity. MAIN METHODS: we performed an intervention cross-sectional study, in which levels of ghrelin, desacyl-ghrelin (DAG), glucose, insulin, ghrelin des-acylation and ghrelin proteolysis were assessed in plasma before and after a test meal in 40 people (n = 21 males) with normal weight (NW, n = 20) or overweight/obesity (OW/OB, n = 20). KEY FINDINGS: Preprandial ghrelin and DAG levels were lower, whereas preprandial ghrelin proteolysis was â¼4.6-fold higher in plasma of males with OW/OB. In males, ghrelin proteolysis positively correlated with glycemia. Ghrelin and DAG levels were also lower in females with OW/OB, but preprandial ghrelin proteolysis was not different between females with NW or OW/OB. Ghrelin and DAG levels decreased postprandially in males and females, independently of BMI, and ghrelin proteolysis increased postprandially â¼2 folds only in individuals with NW. Ghrelin des-acylation remained unaffected by BMI or feeding status in both sexes. SIGNIFICANCE: Current study shows that ghrelin proteolysis increases in males with obesity as well as after meal in lean individuals. Therefore, ghrelin proteolysis may be an important checkpoint and, consequently, a putative pharmacological target to control circulating ghrelin levels in humans.
Assuntos
Grelina , Obesidade , Caracteres Sexuais , Feminino , Humanos , Masculino , Estudos Transversais , Grelina/sangue , Grelina/metabolismo , Insulina , Obesidade/metabolismo , SobrepesoRESUMO
Structural modifications are an important tool for studying the properties of naturally occurring polyphenols. Regarding the preparation of acetyl esters, the presence of hydroxyl groups stabilized by intramolecular hydrogen bonds may pose an obstacle for the peracetylation of these compounds. In this paper, we present a facile protocol for the acetylation of selected polyphenols under mild reaction conditions by using acetic anhydride, catalytic amount 4-dimethylaminopyridine (DMAP) and dimethylformamide (DMF) as solvent. Reaction conditions were adjusted for optimal formation of peracetylated polyphenols while minimizing the formation of byproducts. Butyric anhydride was employed as an alternative acylating agent and showed similar results. Reaction yields varied from 78-97%, and products were obtained in high purity, as determined by LCMS(ESI+), 1H NMR and 13C NMR.
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Anidridos , Acetilação , Espectroscopia de Ressonância Magnética , Catálise , SolventesRESUMO
Protein S-acylation or palmitoylation is a widespread post-translational modification that consists of the addition of a lipid molecule to cysteine residues of proteins through a thioester bond. Palmitoylation and palmitoyltransferases (PATs) have been linked to several types of cancers, diseases of the central nervous system and many infectious diseases where pathogens use the host cell machinery to palmitoylate their effectors. Despite the central importance of palmitoylation in cell physiology and disease, progress in the field has been hampered by the lack of potent-specific inhibitors of palmitoylation in general, and of individual PATs in particular. Herein, we present a yeast-based method for the high-throughput identification of small molecules that inhibit protein palmitoylation. The system is based on a reporter gene that responds to the acylation status of a palmitoylation substrate fused to a transcription factor. The method can be applied to heterologous PATs such as human DHHC20, mouse DHHC21 and also a PAT from the parasite Giardia lamblia. As a proof-of-principle, we screened for molecules that inhibit the palmitoylation of Yck2, a substrate of the yeast PAT Akr1. We tested 3200 compounds and were able to identify a candidate molecule, supporting the validity of our method.
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Aciltransferases/antagonistas & inibidores , Lipoilação , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Saccharomyces cerevisiae/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Giardia lamblia/efeitos dos fármacos , Giardia lamblia/crescimento & desenvolvimento , Giardia lamblia/metabolismo , Ensaios de Triagem em Larga Escala , Humanos , Camundongos , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimento , Especificidade por SubstratoRESUMO
Grass cell walls have hydroxycinnamic acids attached to arabinosyl residues of arabinoxylan (AX), and certain BAHD acyltransferases are involved in their addition. In this study, we characterized one of these BAHD genes in the cell wall of the model grass Setaria viridis. RNAi silenced lines of S. viridis (SvBAHD05) presented a decrease of up to 42% of ester-linked p-coumarate (pCA) and 50% of pCA-arabinofuranosyl, across three generations. Biomass from SvBAHD05 silenced plants exhibited up to 32% increase in biomass saccharification after acid pre-treatment, with no change in total lignin. Molecular dynamics simulations suggested that SvBAHD05 is a p-coumaroyl coenzyme A transferase (PAT) mainly involved in the addition of pCA to the arabinofuranosyl residues of AX in Setaria. Thus, our results provide evidence of p-coumaroylation of AX promoted by SvBAHD05 acyltransferase in the cell wall of the model grass S. viridis. Furthermore, SvBAHD05 is a promising biotechnological target to engineer crops for improved biomass digestibility for biofuels, biorefineries and animal feeding.
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Aciltransferases/metabolismo , Ácidos Cumáricos/metabolismo , Setaria (Planta)/metabolismo , Xilanos/metabolismo , Biomassa , Parede Celular/metabolismo , Genes de Plantas , Redes e Vias Metabólicas , Polissacarídeos/metabolismo , Setaria (Planta)/enzimologia , Setaria (Planta)/genéticaRESUMO
OBJECTIVE: The present report describes the enzymatic acylation of umbelliferone with different vinyl esters as acyl donors biocatalyzed by the commercial lipase Novozym® 435, and the investigation for their antibacterial activity against ATCC and clinical strains isolated from hospital infection sites. RESULTS: The umbelliferone esters (1-5) were synthesized through the acylation reaction of 7-hydroxy-2H-chromen-2-one with different long chain vinyl esters catalyzed by the lipase Novozym 435. The reaction conditions were: 10% Novozym 435; tetrahydrofuran:acetone (3:1) for the reactions with acetate, propionate and butyrate vinyl esters 50-90% conversion, and (9:1) for decanoate and laurate vinyl esters 10-15% conversion; acyl donor/umbelliferone molar ratio of 10:1 and 60 °C. All the umbelliferone esters were characterized NMR and (HRMS). The antibacterial activity of the products were tested using the broth microdilution method in order to determine the minimum inhibitory concentration (MIC). The results displayed by 7-laurate and 7-decanoate-umbelliferone esters showed the highest antibacterial potential, with 1 mM inhibitory activity for ATCC 33591, a methicillin and oxacillin resistant Staphylococcus aureus strain. They were also able to inhibit gram-negative bacterial strains, such as Pseudomonas aeruginosa (MIC 0.5 mM) and Klebsiella pneumoniae (MIC 1 mM). In addition, 7-laurate- and 7-decanoate-umbelliferone esters were able to inhibit all clinical strains (MIC 1 mM; except 7-laurate-umbelliferone in which MIC 0.5 mM against 55a). CONCLUSIONS: This is the first study performing the biocatalysis of umbelliferone followed by the purification of the products and the antibacterial evaluation.
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Infecções Bacterianas/tratamento farmacológico , Ésteres/farmacologia , Lipase/química , Umbeliferonas/farmacologia , Antibacterianos/síntese química , Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Biocatálise , Enzimas Imobilizadas/química , Enzimas Imobilizadas/genética , Ésteres/síntese química , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Lipase/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Transdução de Sinais/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Umbeliferonas/síntese químicaRESUMO
Eukaryotic DNA exist in the nuclei in the form of a complex with proteins called chromatin. Access to the information encoded in the DNA requires the opening of the chromatin. Modulation of the chromatin structure is therefore an important layer of regulation for DNA-templated processes. The basic unit of the chromatin is the nucleosome, which contains DNA wrapped around an octamer of histones, H2A, H2B, H3, and H4. Because histones are a structural part of the nucleosome, its modification can lead to changes in chromatin structure. Amino acid residues in histones could be modified with at least 20 different types of functional groups leading to a vast number of modified residues. Here, an overview of the histone modifications found in plants is provided. We focus mainly in proteomic-based studies either aimed to identify PTMs on purified histones or proteome-wide analysis of particular modifications. The strategies used for cataloging modifications in plants are also described. Profiling of histone modifications is important to begin to understand their functions as mediators of gene regulation in plant biological systems.
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Histonas , Plantas/genética , Processamento de Proteína Pós-Traducional , Proteômica , Cromatina , Histonas/genética , Histonas/metabolismo , Nucleossomos/genéticaRESUMO
Native agave fructans were modified by an acylation reaction with lauric acid. Native and modified fructans were characterized using NMR, FTIR and various physicochemical and functional properties at different pHs were evaluated. NMR and FTIR spectra demonstrated the incorporation of lauric acid in the molecular structure of fructans. Modified agave fructans exhibited a color, moisture and water activity similar to native fructans, but properties such as solubility, swelling capacity, emulsifying activity and foam capacity were significantly modified by the acylation reaction mainly when the samples were analyzed at different pHs. The thermogram of the acylated fructans evidenced significant changes in thermal properties when compared with native fructans and acylated fructans were able to form micellar aggregates. In general, modified fructans showed improved functional properties in comparison with native fructans representing an important opportunity to improve the functionality of the foods in which it is incorporated.
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Agave/química , Frutanos/química , Tensoativos/química , Acilação , Domínio Catalítico , Emulsões , Esterificação , Temperatura Alta , Concentração de Íons de Hidrogênio , Ácidos Láuricos/química , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Tensão Superficial , Água/químicaRESUMO
ß-lactamases are the main molecules responsible for giving bacterial resistance against ß-lactam antibiotics. The study of ß-lactamases has allowed the development of antibiotics capable of inhibiting these enzymes. In this context, extended spectrum ß-lactamase (ESBL) TLA-1 has spread in Escherichia coli and Enterobacter cloacae clinical isolates during the last 30 years in Mexico. In this research, the 3D structures of ESBL TLA-1 and TLA-1 S70G mutant, both ligand-free and in complex with clavulanic acid were determined by X-ray crystallography. Four clavulanic acid molecules were found in the structure of TLA-1, two of those were intermediaries of the acylation process and were localized covalently bound to two different amino acid residues, Ser70 and Ser237. The coordinates of TLA-1 in complex with clavulanic acid shows the existence of a second acylation site, additional to Ser70, which might be extendable to several members of the subclass A ß-lactamases family. This is the first time that two serines involved in binding clavulanic acid has been reported and described to an atomic level.
Assuntos
Ácido Clavulânico/metabolismo , beta-Lactamases/química , beta-Lactamases/metabolismo , Acilação , Cristalografia por Raios X , Ligantes , Modelos Moleculares , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Mutação/genética , Eletricidade EstáticaRESUMO
Protein S-acylation is a reversible post-translational modification involving the addition of fatty acids to cysteines and is catalyzed by transmembrane protein acyltransferases (PATs) mainly expressed at the Golgi complex. In case of soluble proteins, S-acylation confers stable membrane attachment. Myristoylation or farnesylation of many soluble proteins constitutes the initial transient membrane adsorption step prior to S-acylation. However, some S-acylated soluble proteins, such as the neuronal growth-associated protein Growth-associated protein-43 (GAP-43), lack the hydrophobic modifications required for this initial membrane interaction. The signals for GAP-43 S-acylation are confined to the first 13 amino acids, including the S-acylatable cysteines 3 and 4 embedded in a hydrophobic region, followed by a cluster of basic amino acids. We found that mutation of critical basic amino acids drastically reduced membrane interaction and hence S-acylation of GAP-43. Interestingly, acute depletion of phosphatidylinositol 4-phosphate (PtdIns4P) at the Golgi complex reduced GAP-43 membrane binding, highlighting a new, pivotal role for this anionic lipid and supporting the idea that basic amino acid residues are involved in the electrostatic interactions between GAP-43 and membranes of the Golgi complex where they are S-acylated.
Assuntos
Proteína 4 Homóloga a Disks-Large/metabolismo , Proteína GAP-43/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Processamento de Proteína Pós-Traducional , Rede trans-Golgi/metabolismo , Acilação , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Células CHO , Sequência Conservada , Cricetulus , Proteína 4 Homóloga a Disks-Large/química , Proteína 4 Homóloga a Disks-Large/genética , Proteína GAP-43/química , Proteína GAP-43/genética , Interações Hidrofóbicas e Hidrofílicas , Eletricidade Estática , Fatores de Tempo , Rede trans-Golgi/genéticaRESUMO
DHHC palmitoyltransferases (DHHC-PATs) are very peculiar in that, outside the DHHC domain, they are very divergent even across orthologs from closely related species. This represents a challenge for the bioinformatic analyses of these proteins. Sequence-based analyses and predictions require a valid sequence alignment, which for this family of proteins requires extensive manual curation and this is difficult to attain for the nonspecialist. Here we present a simple method for the in silico analysis of the sequence of a particular PAT, that would allow for the identification of important structural features and functional residues in a PAT or PAT family.
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Acetiltransferases , Alinhamento de Sequência , Análise de Sequência de Proteína , Software , Acetiltransferases/química , Acetiltransferases/genética , Motivos de Aminoácidos , Biologia ComputacionalRESUMO
A simple and efficient method to synthesize the immunogenic glycolipid BbGL1 is introduced. Two simple steps were required to obtain the desired product in good yield. First, a highly efficient glycosylation of cholesterol using galactosyl trichloroacetimidate as a donor was performed to produce cholesteryl-ß-d-galactoside. Finally, an efficient palmitoylation on the C6-OH of the galactose of the synthesized saponin using sym-collidine and acyl chloride under microwave heating that produced BbGL1 in good yield. The procedure is a convenient and cheaper alternative to the reported procedures allowing a rapid preparation of multiple analogs and conjugates.
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Glicolipídeos/síntese química , Glicolipídeos/imunologia , Saponinas/síntese química , Saponinas/imunologia , Glicolipídeos/química , Glicosilação , Conformação Molecular , Saponinas/químicaRESUMO
Kex2 is the prototype of a large family of eukaryotic subtilisin-related proprotein-processing proteases that cleave at sites containing pairs of basic residues. Here, we studied the effects of KCl on the individual rate constants of association, dissociation, acylation and deacylation and determined the thermodynamic parameters at each step of the Kex2 reaction. Potassium bound Kex2 with KD=20.3mM. The order in which potassium entered the reaction system modified the effect of activation or inhibition, which depended on the size of the substrate. A possible allosteric potassium binding site at the S6 subsite was involved in activation, and a distant site located between the catalytic domain and the P-domain was involved in inhibition. Potassium decreased the energetic barriers of almost all steps of catalysis. The acylation of Ac-PMYKR-AMC in the absence of potassium was the rate-limiting step. Therefore, for substrates containing a P1-Arg, the deacylation step is not necessarily the rate-limiting event, and other residues at the P' positions may participate in controlling the acylation and deacylation steps. Thus, it is reasonable to conclude that potassium is involved in the processing of the α-mating factor that promotes Ca2+ mobilization by activating a high-affinity Ca2+-influx system to increase the cytosolic [Ca2+], resulting in the activation of channels that are essential for the survival of Saccharomyces cerevisiae cells.
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Potássio/farmacologia , Pró-Proteína Convertases/antagonistas & inibidores , Pró-Proteína Convertases/metabolismo , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/metabolismo , Termodinâmica , Acilação , Cálcio/metabolismo , Potássio/química , Especificidade por SubstratoRESUMO
Feruloylation of arabinoxylan (AX) in grass cell walls is a key determinant of recalcitrance to enzyme attack, making it a target for improvement of grass crops, and of interest in grass evolution. Definitive evidence on the genes responsible is lacking so we studied a candidate gene that we identified within the BAHD acyl-CoA transferase family. We used RNA interference (RNAi) silencing of orthologs in the model grasses Setaria viridis (SvBAHD01) and Brachypodium distachyon (BdBAHD01) and determined effects on AX feruloylation. Silencing of SvBAHD01 in Setaria resulted in a c. 60% decrease in AX feruloylation in stems consistently across four generations. Silencing of BdBAHD01 in Brachypodium stems decreased feruloylation much less, possibly due to higher expression of functionally redundant genes. Setaria SvBAHD01 RNAi plants showed: no decrease in total lignin, approximately doubled arabinose acylated by p-coumarate, changes in two-dimensional NMR spectra of unfractionated cell walls consistent with biochemical estimates, no effect on total biomass production and an increase in biomass saccharification efficiency of 40-60%. We provide the first strong evidence for a key role of the BAHD01 gene in AX feruloylation and demonstrate that it is a promising target for improvement of grass crops for biofuel, biorefining and animal nutrition applications.
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Biomassa , Parede Celular/metabolismo , Coenzima A-Transferases/genética , Ácidos Cumáricos/metabolismo , Genes de Plantas , Setaria (Planta)/enzimologia , Setaria (Planta)/genética , Supressão Genética , Ácidos/metabolismo , Brachypodium/genética , Metabolismo dos Carboidratos , Coenzima A-Transferases/metabolismo , Regulação da Expressão Gênica de Plantas , Inativação Gênica , Hidrólise , Lignina/metabolismo , Espectroscopia de Ressonância Magnética , Tamanho do Órgão , Filogenia , Caules de Planta/metabolismo , Plantas Geneticamente Modificadas , Sementes/anatomia & histologia , Sementes/crescimento & desenvolvimento , Transcriptoma/genética , Xilanos/metabolismoRESUMO
The application of several immobilized lipases has been explored in the enantioselective esterification of (R,S)-2-methylbutyric acid, an insect pheromone precursor. With the use of Candida antarctica B, using hexane as solvent, (R)-pentyl 2-methylbutyrate was prepared in 2 h with c 40%, eep 90%, and E = 35, while Thermomyces lanuginosus leads to c 18%, eep 91%, and E = 26. The (S)-enantiomer was obtained by the use of Candida rugosa or Rhizopus oryzae (2-h reaction, c 34% and 35%, eep 75 and 49%, and E = 10 and 4, respectively). Under optimal conditions, the effect of the solvent, the molar ratio, and the nucleophile were evaluated.
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Butiratos/química , Lipase/metabolismo , Candida , Catálise , Esterificação , Lipase/química , Solventes , EstereoisomerismoRESUMO
ABSTRACT For many years diazocarbonyl compounds have been studied due to their versatility and usability in many chemical transformations. In this review, we summarize the traditional methods to prepare these compounds as well as the new methods and recent improvements in experimental procedures. Moreover, emergence of continuous flow techniques has allowed safer and environmentally friendly procedures for the handling of diazomethane and diazo compounds and will also be a topic in this review.
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Protein S-acylation, also known as palmitoylation, consists of the addition of a lipid molecule to one or more cysteine residues through a thioester bond. This modification, which is widespread in eukaryotes, is thought to affect over 12% of the human proteome. S-acylation allows the reversible association of peripheral proteins with membranes or, in the case of integral membrane proteins, modulates their behavior within the plane of the membrane. This review focuses on the consequences of protein S-acylation on intracellular trafficking and membrane association. We summarize relevant information that illustrates how lipid modification of proteins plays an important role in dictating precise intracellular movements within cells by regulating membrane-cytosol exchange, through membrane microdomain segregation, or by modifying the flux of the proteins by means of vesicular or diffusional transport systems. Finally, we highlight some of the key open questions and major challenges in the field.