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1.
Chinese Journal of Biotechnology ; (12): 1900-1918, 2021.
Article in Chinese | WPRIM | ID: wpr-887771

ABSTRACT

Quercetin 3-O-glycosides (Q3Gs) are important members of quercetin glycosides with excellent pharmacological activities such as anti-oxidation, anti-inflammation, anti-cancer and anti-virus. Two representatives of Q3Gs, rutin and troxerutin, have been developed into clinical drugs, demonstrating Q3Gs have become one of the important sources of innovative drugs. However, the applications of Q3Gs in food and pharmaceutical industries are hampered by its poor bioavailability. Of the known means, selective acylation modification of Q3Gs through enzymatic catalysis to obtain Q3G esters is one of the effective ways to improve its bioavailability. Herein, the enzyme-mediated acylation of Q3Gs were reviewed in details, focusing on the four tool enzymes (acyltransferases, lipases, proteases and esterases) and the whole-cell mediated biotransformation, as well as the effect of acylations on the biological activities of Q3Gs. Furthermore, the highly efficient synthesis and diversification of acylated site for Q3G esters were also discussed. Taken together, this review provides a new perspective for further structural modifications of Q3Gs towards drug development.


Subject(s)
Acylation , Biological Availability , Glycosides , Quercetin , Rutin
2.
Chinese Journal of Biotechnology ; (12): 1887-1899, 2021.
Article in Chinese | WPRIM | ID: wpr-887770

ABSTRACT

Plant serine carboxypeptidase-like acyltransferases (SCPL-AT) have similar structural characteristics and high homology compared to the serine carboxypeptidase. They can transfer the acyl from acyl glucose esters to many natural products, participate in the acylation modification of plant secondary metabolites, enrich the structural diversity of natural products, and improve the physicochemical properties such as water solubility and stability of compounds. This review summarizes the structural characteristics, catalytic mechanism, functional characterization, and biocatalytic applications of SCPL-AT from plants. This will help to promote the functional characterization of these acyltransferase genes and the biosynthesis of useful plant secondary metabolites by synthetic biotechnology.


Subject(s)
Acylation , Acyltransferases/metabolism , Carboxypeptidases/metabolism , Plants/enzymology
3.
Braz. j. med. biol. res ; 47(10): 826-833, 10/2014. graf
Article in English | LILACS | ID: lil-722174

ABSTRACT

O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2±2 vs 7.9±1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4±2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3±2 vs 7.5±2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1±2 vs 7.4±2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time-dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca2+/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction.


Subject(s)
Animals , Male , Muscle, Smooth, Vascular/physiology , Myosin Light Chains/metabolism , Protein Processing, Post-Translational/physiology , Vasoconstriction/physiology , Aorta, Thoracic , Acetylglucosamine/analogs & derivatives , Acetylglucosamine/pharmacology , Acylation/drug effects , Acylation/physiology , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/pharmacology , Azepines/pharmacology , Blotting, Western , Enzyme Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Myosin-Light-Chain Kinase/metabolism , Myosin-Light-Chain Phosphatase/metabolism , Oxazoles/pharmacology , Oximes/pharmacology , Phenylcarbamates/pharmacology , Phenylephrine/agonists , Phosphorylation/drug effects , Phosphorylation/physiology , Rats, Wistar , Ribonucleotides/pharmacology , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , beta-N-Acetylhexosaminidases/antagonists & inhibitors
4.
Article in English | WPRIM | ID: wpr-812691

ABSTRACT

AIM@#To synthesize the baicalein amino acid derivatives and evaluate their cytotoxicity activities in vitro.@*METHODS@#Amino acids were subjected to methylation and aminoacylation reaction, then reacted with formaldehyde and baicalein to synthesize baicalein-8 benzyl amino acid derivatives. Through carboxyl group protection and aminoacylation of amino acid and benzyl protection of baicalein, derivatives of baicalein-6-O-amino acid esters were obtained. All of the target compounds were identified by IR, MS and (1)H NMR.@*RESULTS@#Thirteen novel derivatives were synthesized and characterized. Their cytotoxic activities were assessed by the MTT method on the inhibition of HepG2 cells in vitro.@*CONCLUSION@#Compounds 4c, 4d, 7a and 7b showed a significant increase in cytotoxicity compared with baicalein.


Subject(s)
Acylation , Amino Acids , Chemistry , Cell Proliferation , Flavanones , Chemistry , Toxicity , Hep G2 Cells , Humans , Methylation , Molecular Structure
5.
Article in Chinese | WPRIM | ID: wpr-332779

ABSTRACT

This study was purposed to investigate the effect of phenylhexyl isothiocyanate (PHI) on Wnt/β-catenin signaling pathway, histone acetylation, histone methylation and cell apoptosis in Jurkat cell line. The viability of Jurkat cells after treatment with PHI was tested by MTT. Apoptotic rate of Jurkat cells was measured by flow cytometry. The levels of Wnt/β-catenin related proteins including β-catenin, TCF, c-myc, and cyclinD1, histone acetylated H3 and H4, histone methylated H3K9 and H3K4 were detected by Western blot. The results showed that PHI inhibited the cell growth and induced apoptosis in Jurkat cells in time-and dose-dependent manners. Its IC50 at 48 h was about 20 µmol/L. Expression of histone acetylated H3, H4 and histone methylated H3k4 increased after exposure to PHI for 3 h, while histone methylated H3K9 decreased. Expression of β-catenin was not changed after exposure to PHI for 3 h, but expression of β-catenin, and its cell cycle-related genes such as TCF, c-myc and cyclinD1 decreased after exposure to PHI for 7 h. It is concluded that PHI regulates acetylation and methylation of histone, inhibits Wnt/β-catenin signal pathway, and is able to induce apoptosis and inhibits growth of Jurkat cells.


Subject(s)
Acetylation , Acylation , Cyclin D1 , Metabolism , Histones , Metabolism , Humans , Isothiocyanates , Pharmacology , Jurkat Cells , Methylation , Proto-Oncogene Proteins c-myc , Metabolism , TCF Transcription Factors , Metabolism , Wnt Signaling Pathway , beta Catenin , Metabolism
6.
Toxicological Research ; : 81-86, 2013.
Article in English | WPRIM | ID: wpr-59645

ABSTRACT

Toxicoproteomics integrates the proteomic knowledge into toxicology by enabling protein quantification in biofluids and tissues, thus taking toxicological research to the next level. Post-translational modification (PTM) alters the three-dimensional (3D) structure of proteins by covalently binding small molecules to them and therefore represents a major protein function diversification mechanism. Because of the crucial roles PTM plays in biological systems, the identification of novel PTMs and study of the role of PTMs are gaining much attention in proteomics research. Of the 300 known PTMs, protein acylation, including lysine formylation, acetylation, propionylation, butyrylation, malonylation, succinylation, and crotonylation, regulates the crucial functions of many eukaryotic proteins involved in cellular metabolism, cell cycle, aging, growth, angiogenesis, and cancer. Here, I reviewed recent studies regarding novel types of lysine acylation, their biological functions, and their applicationsin toxicoproteomics research.


Subject(s)
Acetylation , Acylation , Aging , Cell Cycle , Lysine , Protein Processing, Post-Translational , Proteins , Proteomics , Toxicology
7.
Acta Pharmaceutica Sinica ; (12): 64-69, 2011.
Article in English | WPRIM | ID: wpr-353340

ABSTRACT

It was found that psoralen derivative could perform a Friedel-Crafts acylation smoothly with acetic anhydride to give 5'-acetylpsoralen in a 73% yield. In the presence of boron trifluoride etherate, 5'-acetylpsoralen reacted with both aromatic amines and aliphatic amine smoothly to afford 5'-Schiff-base group substituted psoralen derivatives in 72%-92% yields. The novel synthetic method has the advantages of cheap materials, mild reaction conditions, good yields and high regioselectivity in the Friedel-Crafts acylation. Cell viability assay by MTT demonstrates that some of the psoralen derivatives 6 have antiproliferative activities.


Subject(s)
Acylation , Boranes , Chemistry , Cell Line, Tumor , Cell Proliferation , Furocoumarins , Chemistry , Pharmacology , Humans , Molecular Structure , Schiff Bases , Chemistry
8.
Electron. j. biotechnol ; 13(3): 3-4, May 2010. ilus, tab
Article in English | LILACS | ID: lil-577098

ABSTRACT

3 beta-O-phthalic ester of betulinic acid was synthesized from reaction of betulinic acid and phthalic anhydride using lipase as biocatalyst. This ester has clinical potential as an anticancer agent. In this study, artificial neural network (ANN) analysis of Candida antarctica lipase (Novozym 435) -catalyzed esterification of betulinic acid with phthalic anhydride was carried out. A multilayer feed-forward neural network trained with an error back-propagation algorithm was incorporated for developing a predictive model. The input parameters of the model are reaction time, reaction temperature, enzyme amount and substrate molar ratio while the percentage isolated yield of ester is the output. Four different training algorithms, belonging to two classes, namely gradient descent and Levenberg-Marquardt (LM), were used to train ANN. The paper makes a robust comparison of the performances of the above four algorithms employing standard statistical indices. The results showed that the quick propagation algorithm (QP) with 4-9-1 arrangement gave the best performances. The root mean squared error (RMSE), coefficient of determination (R²) and absolute average deviation (AAD) between the actual and predicted yields were determined as 0.0335, 0.9999 and 0.0647 for training set, 0.6279, 0.9961 and 1.4478 for testing set and 0.6626, 0.9488 and 1.0205 for validation set using quick propagation algorithm (QP).


Subject(s)
Acylation , Candida/enzymology , Neural Networks, Computer , Triterpenes/chemistry , Algorithms , Esterification , Solvents
9.
Chinese Journal of Biotechnology ; (12): 2086-2092, 2008.
Article in Chinese | WPRIM | ID: wpr-302869

ABSTRACT

Spiramycin and midecamycin are 16-membered macrolide antibiotics with very similar chemical structures. Spiramycin has three components, namely spiramycin I, II and III. Spiramycin II and III are, respectively, the O-acetyl and propionyl derivatives at C3-hydroxyl group of spiramycin I. Midecamycin has four components, and the C3-hydroxyl group of midecamycin is all O-propionylated. The enzyme adding acyl group(s) at the C3-hydroxyl group during the biosynthesis of spiramycin and midecamycin is 3-O-acyltransferase. The 3-O-acyltransferases for spiramycin and midecamycin are also very similar, and presume to function when exchanged. To explore whether the 3-O-acyltransferase for midecamycin biosynthesis hold still the character of selective and efficient propionylation for spiramycin I at its C3-hydroxyl group, we inserted mdmB, the 3-O-acyltransferase gene from Streptomyces mycarofaciens ATCC 21454 for midecamycin biosynthesis, into a mutant strain of S. spiramyceticus F21, in which the 3-O-acyltransferase gene for spiramycin biosynthesis, sspA, was deleted; and the mdmB was integrated exactly into the chromosomal site where the sspA was deleted. We name this "hybrid" strain as SP-mdmB. HPLC analysis of the spiramycin produced by SP-mdmB showed that spiramycin I was still the major component, although the relative proportions of both spiramycin II and III increased significantly. We thus conclude that MdmB from Streptomyces mycarofaciens ATCC 21454 for midecamyicn biosynthesis do not hold the character of selective and efficient propionylation for spiramycin I within S. spiramyceticus F21, and this character is possibly limited in Streptomyces mycarofaciens ATCC 21454 for midecamycin biosynthesis.


Subject(s)
Acylation , Acyltransferases , Genetics , Metabolism , Culture Media , Genes, Bacterial , Genetic Engineering , Methods , Leucomycins , Spiramycin , Streptomyces , Genetics , Substrate Specificity
10.
Acta Pharmaceutica Sinica ; (12): 111-117, 2007.
Article in English | WPRIM | ID: wpr-281957

ABSTRACT

Even though chemistry is now in place that potentially allows high coupling efficiencies to be attained, successful coupling is usually a challenge when so-called "difficult sequences" is encountered in peptide synthesis. Some factors that affect the coupling efficiency have been discussed and related methods to overcome those obstacles have been introduced in present review. All suggestions proposed here are valuable and also feasible to improve the coupling completeness in both liquid-phase or solid-phase


Subject(s)
Acylation , Amino Acid Sequence , Molecular Structure , Organophosphorus Compounds , Chemistry , Peptide Fragments , Chemistry , Peptides , Chemistry , Proline , Chemistry , Resins, Synthetic , Chemistry , Temperature , Thiazoles , Chemistry , Thiocyanates , Chemistry , Triazoles , Chemistry
11.
Rev. chil. obes ; 6(1): 5-15, 2001. tab
Article in Spanish | LILACS | ID: lil-314845

ABSTRACT

In the last decade, specially after the discovery of leptin, several neuropeptides that regulate energy intake and expenditure have been described in animal models. This has partially unvelied the underlying mechanisms that regulate body composition and weight and therefore a promise of a more effective treatment of obesity and its comorbidities is ad portas


Subject(s)
Humans , Diabetes Mellitus, Type 2 , Insulin Resistance , Obesity , Appetite Regulation/genetics , Fatty Acids/genetics , Acylation , Diabetes Mellitus, Type 2 , Dopamine , Atrial Natriuretic Factor/pharmacology , Hypertension/etiology , Leptin , Lipolysis , Molecular Biology , Mutation/genetics , Neuropeptides/pharmacology , Obesity , Natriuretic Peptide, Brain/pharmacology , Natriuretic Peptide, C-Type/pharmacology , Peroxisome Proliferators , Protein Tyrosine Phosphatases/pharmacology , Receptors, Adrenergic, beta/genetics , Uncoupling Agents
12.
Article in Korean | WPRIM | ID: wpr-160754

ABSTRACT

PURPOSE: Idoxifene is currently entering phase II clinical trials for the treatment of advanced breast cancer. The radiolabeled idoxifene using 123I provides an opportunity for clinical pharmacology with single photon emission computed tomography (SPECT). The purpose of this study was to prepare radiolabeled idoxifene using 123I and to determine its cell uptake of breast cancer cell line. MATERIALS AND METHODS: With a view to evaluating new anticancer drugs, we are investigating the novel antiestrogen pyrrolidino- 4-iodotamoxifen (idoxifene). [123I]Idoxifene has been prepared in no-carrier-added form using a tributyl stannylated precursor which has been synthesized by means of (2-chloroethoxy)benzene with (+/-)-2- phenylbutanoic acid on the basis of previously reported standard methods. The biodistribution and dynamic behavior of the compound were investigated using the comparative breast cancer cell line, MCF-7 (estrogen receptor-positive) and MDA-MB-468 (non-estrogen receptor). RESULTS AND CONCLUSION: Acylation of (2-chloroethoxy)benzene with (+/-)-2-phenylbutanoic acid gave the versatile ketone (81%) which reacted with 1,4-diiodobenzene to give triphenylethylene as a mixture of E and Z geometric isomers, which were separated by the recrystallization in ethanol. The E-isomer was treated with pyrrolidine to give idoxifene (67%). In order to incorporate radioactive iodine into the 4-position, the 4-stannylated precursor was prepared (30%). The yield of radioiodination was 90-92% with a high radiochemical purity greater than 98%. The ratio of tumor uptake of the breast cancer cell line between MCF-7 and MDA-MB-468 was about 1.7.


Subject(s)
Acylation , Breast Neoplasms , Breast , Cell Line , Estrogen Receptor Modulators , Ethanol , Iodine , Pharmacology, Clinical , Tomography, Emission-Computed, Single-Photon
13.
Article in English | IMSEAR | ID: sea-26829

ABSTRACT

A large number of proteins on the eukaryotic cell surface that play an important role in cellular metabolism are covalently modified with fatty acids like palmitic and myristic acids. While some of these proteins have transmembrane spanning segments, many others do not. Early hypothesis was that this co or posttranslational modification helped in membrane-association and the fatty acyl chain provided a stable membrane anchor. We have investigated the structure of peptides with these modifications and also their interaction with membranes. Our results indicate that the fatty acylated peptides, especially when the peptide segment is not hydrophobic, do not have strong affinity for membranes. The recent observations about the dynamic nature of fatty acid acylation as well as the importance of protein-protein interactions for function in fatty-acylated proteins suggest that membrane-association may involve factors other than only the fatty acid, either myristic or palmitic. Revised models depicting the possible role of fatty acids in modulating protein-protein interaction and their dynamics is presented.


Subject(s)
Acylation , Cell Membrane/chemistry , Fatty Acids/chemistry , Lipoproteins/chemistry , Membrane Proteins/chemistry , Myristic Acid/chemistry , Palmitic Acid/chemistry , Peptides/chemistry , Protein Conformation
14.
Indian J Biochem Biophys ; 1996 Oct; 33(5): 343-8
Article in English | IMSEAR | ID: sea-27716

ABSTRACT

The biochemistry and cell biology of covalent attachment of the fatty acids palmitic and myristic to proteins has been the subject of extensive investigations during the past fifteen years. While the site of attachment of fatty acids and the primary structure of proteins around the acylation site have been extensively documented, the exact role of the fatty acids have only been speculated upon. Since fatty acids would prefer to be associated with the lipid bilayer of membranes, it has been assumed that the role of the fatty acid is to provide a stable membrane anchor. This review discusses recent reports in the area of fatty acylation which suggests roles for the fatty acid other than that of a stable membrane anchor.


Subject(s)
Acylation , Acyltransferases/metabolism , Lipid Bilayers/chemistry , Membrane Proteins/chemistry , Models, Chemical , Myristic Acids/metabolism , Palmitic Acids/metabolism , Proteins/chemistry
15.
Indian J Biochem Biophys ; 1994 Dec; 31(6): 454-8
Article in English | IMSEAR | ID: sea-29087

ABSTRACT

Total tRNAs isolated from N2- and NH4(+)-grown Azospirillum lipoferum cells were compared with respect to amino acid acceptance, isoacceptor tRNA species levels and extent of nucleotide modifications. Amino-acylation of these two tRNA preparations with ten different amino acids indicated differences in the relative acceptor activities. Comparison of aminoacyl-tRNA patterns by RPC-5 column chromatography revealed no qualitative differences in the elution profiles. However, quantitative differences in the relative amounts of some isoacceptors were observed. These results indicate that alterations of relative amounts of functional tRNA species occur to match cellular requirements of the bacterial cells using N2 or NH4+ as nitrogen source. In addition, the content of modified nucleotides in total tRNAs of N2- and NH4(+)-grown cells was determined. In the NH4(+)-grown cells, content of most of the modified nucleotides decreased significantly. Based upon these results, the relationship of chargeability of tRNAs to base modifications is discussed.


Subject(s)
Acylation , Amino Acids/metabolism , Azospirillum/drug effects , Nitrogen/pharmacology , Nucleotides/metabolism , Quaternary Ammonium Compounds/pharmacology , RNA Processing, Post-Transcriptional , RNA, Transfer/metabolism
16.
Arch. latinoam. nutr ; 43(2): 157-160, Jun. 1993.
Article in English | LILACS | ID: lil-321684

ABSTRACT

Defatted kernel flour of oil palm, grounded to 60 mesh, was taken as raw material to produce protein concentrates (70.8) protein) which were succinylated at different levels (0.05; 0.2 and 0.6). The extent of acylation was measured as percentage of lysine modification reaching values from 18.4 to 48.6. Protein concentrate functional properties were determined: Water solubility (pH 2-10); water absorption (320); oil absorption (2.2 ml oil/g), emulsion activity and emulsion stability (28-46). The functional properties were enhanced by succinylation if compared with the untreated protein concentrate, however, "in vitro" digestibility was not affected, by succinylation. In summary, the results of this study indicate that acylation using succinyl anhydride can improve the functional properties of oil palm protein concentrate over those without such treatment.


Subject(s)
Flour , Plant Oils/analysis , Plant Proteins/analysis , Dietary Proteins/analysis , Acylation , Solubility , Succinic Anhydrides
17.
Indian J Biochem Biophys ; 1991 Aug; 28(4): 257-62
Article in English | IMSEAR | ID: sea-26743

ABSTRACT

Enzyme protein fluorescence of di-furylacryloyl-glyceraldehyde-3-phosphate dehydrogenase (di-FA-GPDH:lambda max.excitation 290 nm, lambda max.emission 338 nm) is quenched about 28% on saturation with NAD+. Results of fluorometric titration of di-FA-GPDH with NAD+ suggest the presence of two tight and two loose coenzyme binding sites (Kdiss. 0.1 and 6.0 microM, respectively). Initial rates of the NAD(+)-dependent reaction of di-FA-GPDH with arsenate and phosphate and of mono-FA-GPDH with phosphate have been determined at varying coenzyme concentrations. The data suggest that binding of NAD+ at the tight sites does not activate the acyl group for its reaction with the acceptor (phosphate or arsenate). The group transfer reaction is dependent only on NAD+ binding to the loose sites, which carry the acyl group. The large difference in the NAD+ binding affinity to the two types of sites and their different effects on the group transfer reaction impart a sigmoidal shape to the rate versus [NAD+] plots. The sigmoidicity is abolished if the reactive SH groups at the unacylated sites are blocked by carboxymethylation.


Subject(s)
Acylation , Binding Sites , Glyceraldehyde-3-Phosphate Dehydrogenases/chemistry , Kinetics , NAD/metabolism
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