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1.
Anal Bioanal Chem ; 416(12): 3007-3017, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38565719

RESUMO

Enantioseparation of α -hydroxy acids is essential since specific enantiomers of these compounds can be used as disease biomarkers for diagnosis and prognosis of cancer, brain diseases, kidney diseases, diabetes, etc., as well as in the food industry to ensure quality. HPLC methods were developed for the enantioselective separation of 11 α -hydroxy acids using a superficially porous particle-based teicoplanin (TeicoShell) chiral stationary phase. The retention behaviors observed for the hydroxy acids were HILIC, reversed phase, and ion-exclusion. While both mass spectrometry and UV spectroscopy detection methods could be used, specific mobile phases containing ammonium formate and potassium dihydrogen phosphate, respectively, were necessary with each approach. The LC-MS mode was approximately two orders of magnitude more sensitive than UV detection. Mobile phase acidity and ionic strength significantly affected enantioresolution and enantioselectivity. Interestingly, higher ionic strength resulted in increased retention and enantioresolution. It was noticed that for formate-containing mobile phases, using acetonitrile as the organic modifier usually resulted in greater enantioresolution compared to methanol. However, sometimes using acetonitrile with high ammonium formate concentrations led to lengthy retention times which could be avoided by using methanol as the organic modifier. Additionally, the enantiomeric purities of single enantiomer standards were determined and it was shown that almost all standards contained some levels of enantiomeric impurities.


Assuntos
Biomarcadores , Hidroxiácidos , Espectrometria de Massas , Biomarcadores/análise , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Estereoisomerismo , Hidroxiácidos/análise , Hidroxiácidos/química , Espectrofotometria Ultravioleta/métodos , Limite de Detecção , Espectrometria de Massa com Cromatografia Líquida
2.
Nature ; 625(7995): 603-610, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38200312

RESUMO

The genetic code of living cells has been reprogrammed to enable the site-specific incorporation of hundreds of non-canonical amino acids into proteins, and the encoded synthesis of non-canonical polymers and macrocyclic peptides and depsipeptides1-3. Current methods for engineering orthogonal aminoacyl-tRNA synthetases to acylate new monomers, as required for the expansion and reprogramming of the genetic code, rely on translational readouts and therefore require the monomers to be ribosomal substrates4-6. Orthogonal synthetases cannot be evolved to acylate orthogonal tRNAs with non-canonical monomers (ncMs) that are poor ribosomal substrates, and ribosomes cannot be evolved to polymerize ncMs that cannot be acylated onto orthogonal tRNAs-this co-dependence creates an evolutionary deadlock that has essentially restricted the scope of translation in living cells to α-L-amino acids and closely related hydroxy acids. Here we break this deadlock by developing tRNA display, which enables direct, rapid and scalable selection for orthogonal synthetases that selectively acylate their cognate orthogonal tRNAs with ncMs in Escherichia coli, independent of whether the ncMs are ribosomal substrates. Using tRNA display, we directly select orthogonal synthetases that specifically acylate their cognate orthogonal tRNA with eight non-canonical amino acids and eight ncMs, including several ß-amino acids, α,α-disubstituted-amino acids and ß-hydroxy acids. We build on these advances to demonstrate the genetically encoded, site-specific cellular incorporation of ß-amino acids and α,α-disubstituted amino acids into a protein, and thereby expand the chemical scope of the genetic code to new classes of monomers.


Assuntos
Aminoácidos , Aminoacil-tRNA Sintetases , Escherichia coli , Código Genético , RNA de Transferência , Acilação , Aminoácidos/química , Aminoácidos/metabolismo , Aminoacil-tRNA Sintetases/química , Aminoacil-tRNA Sintetases/genética , Aminoacil-tRNA Sintetases/metabolismo , Código Genético/genética , Hidroxiácidos/química , Hidroxiácidos/metabolismo , RNA de Transferência/química , RNA de Transferência/genética , RNA de Transferência/metabolismo , Especificidade por Substrato , Ribossomos/metabolismo , Escherichia coli/enzimologia , Escherichia coli/genética , Escherichia coli/metabolismo
3.
Nature ; 606(7916): 968-975, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35676490

RESUMO

Branched fatty acid (FA) esters of hydroxy FAs (HFAs; FAHFAs) are recently discovered lipids that are conserved from yeast to mammals1,2. A subfamily, palmitic acid esters of hydroxy stearic acids (PAHSAs), are anti-inflammatory and anti-diabetic1,3. Humans and mice with insulin resistance have lower PAHSA levels in subcutaneous adipose tissue and serum1. PAHSA administration improves glucose tolerance and insulin sensitivity and reduces inflammation in obesity, diabetes and immune-mediated diseases1,4-7. The enzyme(s) responsible for FAHFA biosynthesis in vivo remains unknown. Here we identified adipose triglyceride lipase (ATGL, also known as patatin-like phospholipase domain containing 2 (PNPLA2)) as a candidate biosynthetic enzyme for FAHFAs using chemical biology and proteomics. We discovered that recombinant ATGL uses a transacylation reaction that esterifies an HFA with a FA from triglyceride (TG) or diglyceride to produce FAHFAs. Overexpression of wild-type, but not catalytically dead, ATGL increases FAHFA biosynthesis. Chemical inhibition of ATGL or genetic deletion of Atgl inhibits FAHFA biosynthesis and reduces the levels of FAHFA and FAHFA-TG. Levels of endogenous and nascent FAHFAs and FAHFA-TGs are 80-90 per cent lower in adipose tissue of mice in which Atgl is knocked out specifically in the adipose tissue. Increasing TG levels by upregulating diacylglycerol acyltransferase (DGAT) activity promotes FAHFA biosynthesis, and decreasing DGAT activity inhibits it, reinforcing TGs as FAHFA precursors. ATGL biosynthetic transacylase activity is present in human adipose tissue underscoring its potential clinical relevance. In summary, we discovered the first, to our knowledge, biosynthetic enzyme that catalyses the formation of the FAHFA ester bond in mammals. Whereas ATGL lipase activity is well known, our data establish a paradigm shift demonstrating that ATGL transacylase activity is biologically important.


Assuntos
Aciltransferases , Ésteres , Ácidos Graxos , Hidroxiácidos , Aciltransferases/genética , Aciltransferases/metabolismo , Tecido Adiposo/química , Tecido Adiposo/metabolismo , Animais , Diglicerídeos , Esterificação , Ésteres/química , Ésteres/metabolismo , Ácidos Graxos/biossíntese , Ácidos Graxos/química , Humanos , Hidroxiácidos/química , Hidroxiácidos/metabolismo , Resistência à Insulina , Camundongos , Triglicerídeos
4.
Int J Biol Macromol ; 177: 166-175, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33607136

RESUMO

The present work aims to prepare Chitosan (CS)/Guar gum (GG)/Poly(vinyl alcohol) (PVA) cross-linked with Hydroxy citric acid (HCA) (CGPH active film) by solvent casting technique. The influence of HCA on different CS/PVA ratio (1:3, 1:1, 3:1) in presence of the fixed amount of GG (0.2%) was investigated. The analysis of the results showed that the addition of HCA to the different ratio of CS/PVA increased the degradation temperature and improved the mechanical properties of CGPH active films. FTIR spectra and XRD analysis revealed strong interactions among the components of CGPH active films. The analysis of SEM images and water contact angle suggested a compact, dense film surface with hydrophobic nature. Further, all the active films have shown a decrease in water vapour permeability (WVP) and acted as a barrier to UV-light. CGPH active films effectively inhibited the growth of S. aureus and E. coli bacteria. With all these features the CGPH active films can find application in food packaging.


Assuntos
Quitosana/química , Ácido Cítrico/química , Galactanos/química , Hidroxiácidos/química , Mananas/química , Gomas Vegetais/química , Álcool de Polivinil/química , Antibacterianos/química , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Embalagem de Alimentos/métodos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Solventes/química , Staphylococcus aureus/efeitos dos fármacos , Vapor , Temperatura
5.
Int J Mol Sci ; 22(2)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440780

RESUMO

Since the European Union (EU) announced their animal testing ban in 2013, all animal experiments related to cosmetics have been prohibited, creating a demand for alternatives to animal experiments for skin studies. Here, we investigated whether an ex vivo live porcine skin model can be employed to study the safety and skin barrier-improving effects of hydroxyacids widely used in cosmetics for keratolytic peels. Glycolic acid (1-10%), salicylic acid (0.2-2%), and lactobionic acid (1.2-12%) were used as representative substances for α-hydroxyacid (AHA), ß-hydroxyacid (BHA), and polyhydroxyacid (PHA), respectively. When hydroxyacids were applied at high concentrations on the porcine skin every other day for 6 days, tissue viability was reduced to 50-80%, suggesting that the toxicity of cosmetic ingredients can be evaluated with this model. Based on tissue viability, the treatment scheme was changed to a single exposure for 20 min. The protective effects of a single exposure of hydroxyacids on skin barrier function were evaluated by examining rhodamine permeability and epidermal structural components of barrier function using immunohistochemistry (IHC) and immunofluorescence (IF) staining. Lactobionic acid (PHAs) improved skin barrier function most compared to other AHAs and BHAs. Most importantly, trans-epidermal water loss (TEWL), an important functional marker of skin barrier function, could be measured with this model, which confirmed the significant skin barrier-protective effects of PHAs. Collectively, we demonstrated that the ex vivo live full-thickness porcine skin model can be an excellent alternative to animal experiments for skin studies on the safety and efficacy of cosmetic ingredients.


Assuntos
Fenômenos Fisiológicos da Pele , Pele/metabolismo , Animais , Biomarcadores , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Imunofluorescência , Histocitoquímica , Humanos , Hidroxiácidos/química , Hidroxiácidos/farmacologia , Técnicas In Vitro , Permeabilidade , Rodaminas/farmacologia , Ácido Salicílico/química , Ácido Salicílico/farmacologia , Pele/citologia , Pele/efeitos dos fármacos , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Suínos , Técnicas de Cultura de Tecidos
6.
Sci Rep ; 10(1): 18123, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093595

RESUMO

Isomerization reactions are fundamental in biology. Lactate racemase, which isomerizes L- and D-lactate, is composed of the LarA protein and a nickel-containing cofactor, the nickel-pincer nucleotide (NPN). In this study, we show that LarA is part of a superfamily containing many different enzymes. We overexpressed and purified 13 lactate racemase homologs, incorporated the NPN cofactor, and assayed the isomerization of different substrates guided by gene context analysis. We discovered two malate racemases, one phenyllactate racemase, one α-hydroxyglutarate racemase, two D-gluconate 2-epimerases, and one short-chain aliphatic α-hydroxyacid racemase among the tested enzymes. We solved the structure of a malate racemase apoprotein and used it, along with the previously described structures of lactate racemase holoprotein and D-gluconate epimerase apoprotein, to identify key residues involved in substrate binding. This study demonstrates that the NPN cofactor is used by a diverse superfamily of α-hydroxyacid racemases and epimerases, widely expanding the scope of NPN-dependent enzymes.


Assuntos
Bactérias/enzimologia , Proteínas de Bactérias/metabolismo , Hidroxiácidos/química , Níquel/metabolismo , Nucleotídeos/metabolismo , Racemases e Epimerases/metabolismo , Proteínas de Bactérias/química , Cristalografia por Raios X , Modelos Moleculares , Níquel/química , Nucleotídeos/química , Conformação Proteica , Racemases e Epimerases/química
7.
Int J Biol Macromol ; 163: 298-308, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32603731

RESUMO

Molecular properties and biological functions of Pyrenaican SF-1 as a novel biological macromolecule extracted from a fungal isolate were studied. The isolate was identified as Daldinia pyrenaica on the basis of 5.8S rDNA sequencing. Pyrenaican SF-1 was obtained from the culture filtrate of the fungal isolate. The partial characterization of biochemical structure of Pyrenaican SF-1 was conducted. The fungal extract was also tested for the treatment of AGS, MDA and HeLa cell lines to assess cells proliferation, cells cycle and apoptosis. Furthermore, Pyrenaican SF-1 extract was tested for its antibacterial and antioxidant activity. Initial chemical analysis revealed that Pyrenaican SF-1 extract was composed of various monosaccharides such as d-glucose, D- mannitol, D-arabinose and ß-D-ribopyranose. In vitro study indicated that Pyrenaican SF-1 could effectively elevate percentage of apoptosis and necrosis of cancer cells and block cell cycle phase of the control group. The fungal extract could inhibit proliferation of Hela and MDA cell up to 67% and 56%, respectively. Moreover, Pyrenaican SF-1 represented a strong antioxidant activity compared to that one obtained from vitamin C. On the other hand, Pyrenaican SF-1 exhibited growth inhibitory effects against different Gram-negative and Gram-positive bacterial strains. Pyrenaican SF-1 can be considered as a bioactive macromolecule with promising application in pharmaceutical and medical sectors.


Assuntos
Ascomicetos/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hidroxiácidos/química , Hidroxiácidos/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Viscosidade , beta Caroteno
8.
Chemistry ; 26(55): 12674-12683, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32432817

RESUMO

The outcome of ring-expansion reactions based on amino/hydroxyacid side-chain insertion is strongly dependent on ring size. This manuscript, which builds upon our previous work on Successive Ring Expansion (SuRE) methods, details efforts to better define the scope and limitations of these reactions on lactam and ß-ketoester ring systems with respect to ring size and additional functionality. The synthetic results provide clear guidelines as to which substrate classes are more likely to be successful and are supported by computational results, using a density functional theory (DFT) approach. Calculating the relative Gibbs free energies of the three isomeric species that are formed reversibly during ring expansion enables the viability of new synthetic reactions to be correctly predicted in most cases. The new synthetic and computational results are expected to support the design of new lactam- and ß-ketoester-based ring-expansion reactions.


Assuntos
Aminoácidos , Lactamas , Aminoácidos/química , Hidroxiácidos/química , Lactamas/química
9.
Biotechnol Lett ; 42(8): 1547-1558, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32246345

RESUMO

Microbial production of hydroxy fatty acids (HFAs) was widely studied because of important biological properties of HFAs. Among microorganisms producing HFAs, Pseudomonas aeruginosa PR3 was well known to produce various HFAs from different unsaturated fatty acids. Recently, a new variant species of P. aeruginosa PR3 was isolated and characterized, showing improved efficiency for producing 7,10-dihydroxy-8(E)-octadecenoic acid from oleic acid. In this study, we report the production of 7,10,12-trihydroxy-8(E)-octadecenoic acid (TOD) from ricinoleic acid by the newly isolated P. aeruginosa KNU-2B. TOD was efficiently produced from ricinoleic acid by KNU-2B with the maximum conversion yield of 56.7% under the optimum reaction conditions of pH 8.0 and 48-h incubation at 27 °C, 150 rpm. Under optimized reaction conditions, maximum TOD production reached 340.3 mg/100 mL of the culture. However, requirement of nutritional factors by KNU-2B for production of TOD were considerably different from those by PR3 strain.


Assuntos
Hidroxiácidos , Ácidos Oleicos , Pseudomonas aeruginosa/metabolismo , Ácidos Ricinoleicos , Hidroxiácidos/análise , Hidroxiácidos/química , Hidroxiácidos/metabolismo , Ácidos Oleicos/análise , Ácidos Oleicos/química , Ácidos Oleicos/metabolismo , Ácidos Ricinoleicos/química , Ácidos Ricinoleicos/metabolismo
10.
Methods Mol Biol ; 2133: 119-140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32144665

RESUMO

The chemical synthesis of proteins allows for the precise control of structural information at the atomic level, overcoming the limits of protein expression. Peptide hydrazides are widely used as thioester equivalents in the total chemical synthesis and semisynthesis of proteins as they can be easily prepared using standard solid phase peptide synthesis (SPPS) and recombinant peptide techniques. Via treatment with NaNO2 and subsequent thiolysis, peptide hydrazides can be rapidly converted to peptide thioesters, which then selectively react with recombinant protein containing an N-terminal cysteine (Cys) to form a native peptide bond, thereby linking the two peptide segments without isolating any intermediates.


Assuntos
Peptídeos/química , Proteínas/síntese química , Técnicas de Síntese em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão , Cisteína/química , Ésteres/química , Hidrazinas/química , Hidroxiácidos/química , Proteínas/química , Proteínas Recombinantes/química , Espectrometria de Massas por Ionização por Electrospray , Compostos de Sulfidrila/química
11.
Curr Opin Chem Biol ; 55: 119-126, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32087550

RESUMO

The introduction of fluorine atoms into organic molecules has received considerable attention as these organofluorines have often found widespread applications in bioorganic chemistry, medicinal chemistry and biomaterial science. Despite innovation of synthetic C-F forming methodologies, selective fluorination is still extremely challenging. Therefore, a biotransformation approach using fluorine biocatalysts is needed to selectively introduce fluorine into structurally diverse molecules. Yet, there are few ways that enable incorporation of fluorine into structurally complex bioactive molecules. One is to extend the substrate scope of the existing enzyme inventory. Another is to expand the biosynthetic pathways to accept fluorinated precursors for producing fluorinated bioactive molecules. Finally, an understanding of the physiological roles of fluorometabolites in the producing microorganisms will advance our ability to engineer a microorganism to produce novel fluorinated commodities. Here, we review the fluorinase biotechnology and fluorine biocatalysts that incorporate fluorine motifs to generate fluorinated molecules, and highlight areas for future developments.


Assuntos
Proteínas de Bactérias/metabolismo , Flúor/química , Flúor/metabolismo , Oxirredutases/metabolismo , Biocatálise , Biotransformação , Halogenação , Hidroxiácidos/química , Estrutura Molecular , Estereoisomerismo , Transaminases/metabolismo
12.
Chem Commun (Camb) ; 56(16): 2495-2498, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32003367

RESUMO

Herein, we report the photocatalytic decarboxylative alkenylation reactions of N-(acyloxy)phthalimide derived from α-amino and α-hydroxy acids with 1,1-diarylethene, and with cinnamic acid derivatives through double decarboxylation, using sodium iodide and triphenylphosphine as redox catalysts. The reaction proceeds under mild irradiation conditions with visible blue light (440 nm or 456 nm) in an acetone solvent without recourse to transition-metal or organic dye based photoredox catalysts. The reaction proceeds via photoactivation of a transiently self-assembled chromophore from N-(acyloxy)phthalimide and NaI/PPh3. Solvation plays a crucial role in the reactivity.


Assuntos
Aminoácidos/química , Hidroxiácidos/química , Compostos Organofosforados/química , Iodeto de Sódio/química , Alquilação , Catálise , Descarboxilação , Estrutura Molecular , Oxirredução , Processos Fotoquímicos
13.
Food Res Int ; 129: 108879, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32036935

RESUMO

The volatile aroma compounds of traditional Chinese rose vinegar were identified by headspace solid-phase micro extraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) and GC-MS-olfactometry (GC-MS-O), and the metabolites were identified by silylation-GC-MS in this study. A total of 48 and 76 kinds of flavors and metabolites, respectively were detected in this study. Quantitative analysis showed that aldehydes and acids were present in relatively high amounts. Furthermore, the data colleted by the calculated odor activity values (OAVs) suggested that aldehydes are likely to contribute greatly to the aroma of traditional Chinese rose vinegar, especially, nonanal (OAV: 133, rose), 3-methyl-butanal (OAV: 57, apple-like), decanal (OAV: 23, orange peel), heptanal (OAV: 17, fruity), and dodecanal (OAV: 4-9, violet scents). Moreover, among the detected nonvolatile acids, 14 kinds of hydroxy acids, such as lactic acid, citric acid, 3-phenyllactic acid (PLA) and d-gluconic acid were detected in rose vinegar. The acids provide a well buffer system, not only greatly reduce the irritation of acetic acid, but also improve the flavor of rose vinegar. This study suggests that the fragrance and sour notes in rose vinegar are from aldehydes and hydroxy acids.


Assuntos
Ácido Acético/análise , Aldeídos/química , Aromatizantes/química , Hidroxiácidos/química , Rosa/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Odorantes , Paladar
14.
J Am Chem Soc ; 142(3): 1501-1509, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31895981

RESUMO

Chemoselective reactions are a highly desirable approach to generate well-defined functional macromolecules. Their extraordinary efficiency and selectivity enable the development of flawless structures, such as dendrimers, with unprecedented structure-to-property capacity but with typically tedious synthetic protocols. Here we demonstrate the potency of chemoselective reactions to accomplish sequence-controlled heterolayered dendrimers. An accurate accelerated design of bis-MPA monomers with orthogonally complementary moieties and a wisely selected chemical toolbox generated highly complex monodisperse dendrimers through simplified protocols. The versatility of the strategy was proved by obtaining different dendritic families with different properties after altering the order of addition of the monomers. Moreover, we evaluated the feasibility of the one-pot approach toward these heterolayered dendrimers as proof-of-concept.


Assuntos
Dendrímeros/química , Dendrímeros/síntese química , Hidroxiácidos/química , Estudo de Prova de Conceito , Propionatos/química
15.
Angew Chem Int Ed Engl ; 59(12): 4869-4872, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-31912947

RESUMO

Flavoprotein oxidases can catalyze oxidations of alcohols and amines by merely using molecular oxygen as the oxidant, making this class of enzymes appealing for biocatalysis. The FAD-containing (FAD=flavin adenine dinucleotide) alcohol oxidase from P. chrysosporium facilitated double and triple oxidations for a range of aliphatic diols. Interestingly, depending on the diol substrate, these reactions result in formation of either lactones or hydroxy acids. For example, diethylene glycol could be selectively and fully converted into 2-(2-hydroxyethoxy)acetic acid. Such a facile cofactor-independent biocatalytic route towards hydroxy acids opens up new avenues for the preparation of polyester building blocks.


Assuntos
Oxirredutases do Álcool/metabolismo , Álcoois/metabolismo , Flavoproteínas/metabolismo , Hidroxiácidos/metabolismo , Oxirredutases do Álcool/química , Álcoois/química , Basidiomycota/enzimologia , Biocatálise , Flavoproteínas/química , Hidroxiácidos/química , Estrutura Molecular , Oxirredução
16.
Acta Crystallogr C Struct Chem ; 76(Pt 1): 1-9, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31919301

RESUMO

Depsipeptides and cyclodepsipeptides are analogues of the corresponding peptides in which one or more amide groups are replaced by ester functions. Reports of crystal structures of linear depsipeptides are rare. The crystal structures and conformational analyses of four depsipeptides with an alternating sequence of an α,α-disubstituted α-amino acid and an α-hydroxy acid are reported. The molecules in the linear hexadepsipeptide amide in (S)-Pms-Acp-(S)-Pms-Acp-(S)-Pms-Acp-NMe2 acetonitrile solvate, C47H58N4O9·C2H3N, (3b), as well as in the related linear tetradepsipeptide amide (S)-Pms-Aib-(S)-Pms-Aib-NMe2, C28H37N3O6, (5a), the diastereoisomeric mixture (S,R)-Pms-Acp-(R,S)-Pms-Acp-NMe2/(R,S)-Pms-Acp-(R,S)-Pms-Acp-NMe2 (1:1), C32H41N3O6, (5b), and (R,S)-Mns-Acp-(S,R)-Mns-Acp-NMe2, C30H37N3O6, (5c) (Pms is phenyllactic acid, Acp is 1-aminocyclopentanecarboxylic acid and Mns is mandelic acid), generally adopt a ß-turn conformation in the solid state, which is stabilized by intramolecular N-H...O hydrogen bonds. Whereas ß-turns of type I (or I') are formed in the cases of (3b), (5a) and (5b), which contain phenyllactic acid, the torsion angles for (5c), which incorporates mandelic acid, indicate a ß-turn in between type I and type III. Intermolecular N-H...O and O-H...O hydrogen bonds link the molecules of (3a) and (5b) into extended chains, and those of (5a) and (5c) into two-dimensional networks.


Assuntos
Aminoácidos/química , Depsipeptídeos/química , Hidroxiácidos/química , Amidas/química , Cristalografia por Raios X , Ligação de Hidrogênio , Conformação Proteica , Análise Espectral/métodos
17.
Macromol Rapid Commun ; 41(1): e1900560, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31793732

RESUMO

This review summarizes the current literature regarding stereocomplexation of different polyesters based on α- as well as ß-hydroxy acids beyond the well-known poly(lactic acid). Representing the initial step toward stereocomplexation, synthetic approaches needed to obtain and analyze isotactic polyesters are summarized. The basic technologies for the preparation and characterization of the respective stereocomplexes (SCs) are described, and published material properties are related to the structure of the respective polyesters. The variety of available SC materials is very limited despite the multiple options provided by state-of-the-art stereoselective monomer synthesis and polymerization methods. A combination of knowledge from the three scientific areas (i.e., organic chemistry, synthetic macromolecular chemistry, and materials science) thus has enormous potential to create novel materials with additional features enabled by the introduction of functional moieties to such materials besides the adjustment of thermal as well as mechanical properties.


Assuntos
Poliésteres/química , Materiais Biocompatíveis/química , Reação de Cicloadição , Hidroxiácidos/química , Poliésteres/síntese química , Polimerização , Estereoisomerismo
18.
Biotechnol Appl Biochem ; 67(3): 354-365, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31746015

RESUMO

One-pot synthesis of sugar-functionalized oligomeric caprolactone was carried out by lipase-catalyzed esterification of ε-caprolactone (ECL) with methyl-d-glucopyranoside (MGP) followed by the elongation of functionalized oligomer chain. Functionalization was performed in a custom-fabricated glass reactor equipped with Rushton turbine impeller and controlled temperature at 60 °C using tert-butanol as reaction medium. The overall reaction steps include MGP esterification of ECL monomer and its subsequent elongation by free 6-hydroxyhexanoate monomer units. A ping-pong bi-bi mechanism without ternary complex was proposed for esterification of ECL and MGP with apparent values of kinetic constant, namely maximal velocity (Vmax ), Michaelis constant for MGP (KmMGP ), and Michaelis constant for ECL (KmECL ) at 3.848 × 10-3  M H-1 , 8.189 × 10-2  M, and 6.050 M, respectively. Chain propagation step of MGP-functionalized ECL oligomer exhibits the properties of living polymerization mechanism. Linear relationship between conversion (%) and number average molecular weight, Mn (g mol-1 ), of functionalized oligomer was observed. Synthesized functionalized oligomer showed narrow range of molecular weight from 1,400 to 1,600 g mol-1 with more than 90% conversion achieved. Structural analysis confirmed the presence of covalent bond between the hydroxyl group in MGP with carboxyl end group of ECL oligomer.


Assuntos
Caproatos/metabolismo , Hidroxiácidos/metabolismo , Lactonas/metabolismo , Lipase/metabolismo , Metilglicosídeos/metabolismo , Biocatálise , Caproatos/química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Esterificação , Hidroxiácidos/química , Lactonas/química , Lipase/química , Metilglicosídeos/química , Estrutura Molecular
19.
Nucl Med Biol ; 76-77: 28-35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31678899

RESUMO

INTRODUCTION: Hydrogen sulfide (H2S) defined as the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO) is an important mediator of various physiological functions. Although various H2S-imaging techniques using fluorescence and luminescence have been developed, only one radionuclide imaging using 64Cu-labeled cyclen complex was reported. Thus, we tried to develop 99mTc-labeled H2S imaging agents. METHODS: Various α-hydroxy acids such as glycolate, L-lactate, D-lactate, D-gluconate, D-glucoheptonate, D-glucuronate, D-glucarate, and citrate were labeled with 99mTc in the presence of stannous chloride. The labeled compounds were incubated with 0.2 mM of NaHS, and reactive sulfur species and then analyzed by ITLC/normal saline to detect the formation of insoluble complex. Matrigels containing various concentrations of NaHS were xenografted on the shoulder of normal mice, and an imaging study was performed after intravenous injection of [99mTc]Tc-gluconate. We also obtained autoradiography image of a rat brain with a temporary brain ischemia after intravenous injection of [99mTc]Tc-gluconate. RESULTS: [99mTc]Tc-gluconate showed the highest formation of insoluble complex (87.8 ±â€¯3.6%) after incubation with 0.2 mM NaHS. The other reactive species such as glutathione, cysteine, sulfite, sulfate, thiosulfate, and NO did not form insoluble complex representing the reaction being specific to H2S. The Matrigel containing 2 µmol NaHS showed uptake of [99mTc]Tc-gluconate, which proved the feasibility as the specific H2S imaging agent in vivo. Temporary ischemic lesion of rat brain showed high radioactivity accumulation representing the feasibility as endogenous H2S imaging agents. CONCLUSION: We proved that 99mTc-labeled α-hydroxy acid especially [99mTc]Tc-gluconate is a novel endogenous H2S imaging agent, which might contribute to study and diagnosis of various diseases related with inflammation and hypoxia.


Assuntos
Gasotransmissores/metabolismo , Sulfeto de Hidrogênio/metabolismo , Hidroxiácidos/química , Compostos de Organotecnécio/química , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Animais , Autorradiografia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Linhagem Celular Tumoral , Humanos , Ratos
20.
Molecules ; 24(22)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717454

RESUMO

Endophytes have been recognized as a source for structurally novel and biologically active secondary metabolites. Among the host plants for endophytes, some medicinal plants that produce pharmaceuticals have been reported to carry endophytes, which could also produce bioactive secondary metabolites. In this study, the medicinal plant Aconitum carmichaeli was selected as a potential source for endophytes. An endophytic microorganism, Aureobasidium pullulans AJF1, harbored in the flower of Aconitum carmichaeli, was cultured on a large scale and extracted with an organic solvent. Extensive chemical investigation of the extracts resulted in isolation of three lipid type compounds (1-3), which were identified to be (3R,5R)-3,5-dihydroxydecanoic acid (1), (3R,5R)-3-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-5-hydroxydecanoic acid (2), and (3R,5R)-3-(((3R,5R)-5-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-3-hydroxydecanoyl)oxy)-5-hydroxydecanoic acid (3) by chemical methods in combination with spectral analysis. Compounds 2 and 3 had new structures. Absolute configurations of the isolated compounds (1-3) were established using modified Mosher's method together with analysis of NMR data for their acetonide derivatives. All the isolates (1-3) were evaluated for antibiotic activities against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and their cytotoxicities against MCF-7 cancer cells. Unfortunately, they showed low antibiotic activities and cytotoxic activities.


Assuntos
Ascomicetos/metabolismo , Ácidos Decanoicos/química , Ácidos Decanoicos/metabolismo , Hidroxiácidos/química , Hidroxiácidos/metabolismo , Aconitum/genética , Aconitum/metabolismo , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Ascomicetos/genética , Bactérias/efeitos dos fármacos , Ácidos Decanoicos/síntese química , Ácidos Decanoicos/farmacologia , Humanos , Hidroxiácidos/síntese química , Hidroxiácidos/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular
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