21675-62-7Relevant articles and documents
Kurahamide, a cyclic depsipeptide analog of dolastatin 13 from a marine cyanobacterial assemblage of Lyngbya sp.
Iwasaki, Arihiro,Sumimoto, Shinpei,Ohno, Osamu,Suda, Shoichiro,Suenaga, Kiyotake
, p. 609 - 613 (2014)
Kurahamide, a new dolastatin 13 analog, was isolated from a marine cyanobacterial assemblage, consisting mostly of Lyngbya sp. Its gross structure was elucidated by spectroscopic analysis, and the stereochemistries were assigned based on a chiral HPLC analysis of hydrolysis products. Kurahamide strongly inhibited elastase and chymotrypsin in vitro. In addition, kurahamide moderately inhibited the growth of human cancer cells, including HeLa and HL60 cells.
Purification and characterization of L-glutaminase enzyme from camel liver: Enzymatic anticancer property
Maharem, Tahany M.,Emam, Manal A.,Said, Youssef A.
, p. 1213 - 1222 (2020)
L-Glutaminase has gained an important attention as glutamine-depleting enzyme in treatment of various cancers. Therefore, this study aimed to purify, characterize and investigate antitumor activity of L-glutaminase from camel liver mitochondria (CL-Glu), since no available information about CL-Glu from camel. CL-Glu was purified using cell fractionation, ultrafiltration, DEAE-and CM-cellulose chromatography columns. The purified CL-Glu was a monomer with a molecular weight of 70 ± 3 kDa, isoelectric point of 7.2, optimum temperature of 70 °C and it was active over a broad pH range with a pH optimum at pH 8.0. Its activity had a clear dependence on phosphate ions. The studied enzyme showed sigmoidal kinetics, indicated its allosteric behavior with Km of 36 ± 4 mM and Hill coefficient of 1.5 which suggested a positive cooperatively of active sites. The purified L-glutaminase exerted antitumor activity against different cell lines with the highest cytotoxic activity against Hepatocellular carcinoma cell line (HepG-2) with an IC50 value of 152 μg/ml. In conclusion, L-glutaminase was purified from camel liver using simple methods and its unique properties such as stability at both wide pH range and at high temperature along with its relatively low molecular weight, facilitated its usage in medical applications as antitumor drug.
N5-(4-HYDROXYBENZYL) GLUTAMINE, 4-HYDROXYBENZYLAMINE AND 4-HYDROXYBENZYLGLUCOSINOLATE IN SINAPIS SPECIES
Larsen, Lone Melchior,Olsen, Ole,Pedersen, Haastrup, Lars,Soerensen, Hilmer
, p. 895 - 896 (1984)
N5-(4-hydroxybenzyl) glutamine has been isolated from Sinapis alba L. and S. arvensis L.The identification is based on data obtained by HPLC, paper chromatography, high voltage electrophoresis, UV and NMR spectroscopy of the amide and its degra
A thermodynamic study of the hydrolysis of L-glutamine to (L-glutamate + ammonia) and of L-asparagine to (L-aspartate + ammonia)
Goldberg,Kishore,Kishore,Tewari
, p. 1077 - 1090 (2000)
Calorimetric enthalpies of reaction were measured for the two enzyme-catalyzed reactions, i.e., L-glutamine(aq) + H2O(l) = L-glutamate(aq) + ammonia(aq) (1) and L-asparagine(aq) + H2O(l) = L-aspartate(aq) + ammonia(aq) (2). The standard molar enthalpies for reference reactions involving specific species were computed using an equilibrium model that considered the multiplicity of ionic forms of the reactants and products. Using the thermodynamic quantities obtained for the reference reactions, the values of the apparent equilibrium constant for reactions 1 and 2 at 311.15 K and pH 7 were 250. In performing these calculations, it was assumed that there was no binding of Mg2+(aq) to any of the species involved in the reactions 1 and 2. The standard transformed Gibbs energy changes for these two reactions under physiological conditions were both -14 kJ/mole. The thermodynamic results were discussed with respect to the structural changes involved in these reactions.
Jenny,Leuthardt
, p. 78,79-84 (1961)
Fowden,L.,Smith,A.
, p. 809 - 819 (1968)
Kinetic and mechanism of reactions of L-α-glutamic acid and L-Glutamine with pyridoxal
Pishchugin,Tuleberdiev
, p. 1362 - 1366 (2014)
The kinetics and mechanisms of condensation of pyridoxal with L-α-glutamic acid and L-glutamine were studied by UV spectroscopy and polarimetry. L-α-Glutamic acid reacts with pyridoxal to form a Schiff base whose subsequent hydrolysis gives rise to pyridoxamine and α-ketoglutaric acid. The reaction of Lglutamine with pyridoxal involves the Γ-NH 2 group and affords a Schiff base whose subsequent hydrolysis gives rise to pyridoxamine and L-α-glutamic acid.
Helices on Interdomain Interface Couple Catalysis in the ATPPase Domain with Allostery in Plasmodium falciparum GMP Synthetase
Shivakumaraswamy, Santosh,Pandey, Nivedita,Ballut, Lionel,Violot, Sébastien,Aghajari, Nushin,Balaram, Hemalatha
, p. 2805 - 2817 (2020)
GMP synthetase catalyses the conversion of XMP to GMP through a series of reactions that include hydrolysis of Gln to generate ammonia in the glutamine amidotransferase (GATase) domain, activation of XMP to adenyl-XMP intermediate in the ATP pyrophosphatase (ATPPase) domain and reaction of ammonia with the intermediate to generate GMP. The functioning of GMP synthetases entails bidirectional domain crosstalk, which leads to allosteric activation of the GATase domain, synchronization of catalytic events and tunnelling of ammonia. Herein, we have taken recourse to the analysis of structures of GMP synthetases, site-directed mutagenesis and steady-state and transient kinetics on the Plasmodium falciparum enzyme to decipher the molecular basis of catalysis in the ATPPase domain and domain crosstalk. Our results suggest an arrangement at the interdomain interface, of helices with residues that play roles in ATPPase catalysis as well as domain crosstalk enabling the coupling of ATPPase catalysis with GATase activation. Overall, the study enhances our understanding of GMP synthetases, which are drug targets in many infectious pathogens.
An equilibrium and calorimetric study of some transamination reactions
Tewari, Yadu B.,Kishore, Nand,Goldberg, Robert N.,Luong, Tinh N.
, p. 777 - 793 (1998)
Apparent equilibrium constants and calorimetric enthalpies of reaction have been measured for the following enzyme-catalysed biochemical reactions at the temperature 298.15 K: L-alanine(aq) + 2-oxoglutarate(aq) = pyruvate(aq) + L-glutamate(aq); L-tyrosine(aq) + 2-oxoglutarate(aq) = 4-hydroxyphenylpyruvate(aq) + L-glutamate(aq); and L-phenylalanine(aq) + 2-oxoglutarate(aq) = phenylpyruvate(aq) + L-glutamate(aq). The results are used to calculate equilibrium constants and standard molar enthalpy, entropy, and Gibbs energy changes for reference reactions involving specific species. Apparent equilibrium constants and standard transformed Gibbs energy changes for these reactions under physiological conditions have also been calculated. The results are discussed in terms of the changes in chemical bonding characteristic of transamination reactions.
Structure of homoplatensimide A: a potential key biosynthetic intermediate of platensimycin isolated from Streptomyces platensis
Jayasuriya, Hiranthi,Herath, Kithsiri B.,Ondeyka, John G.,Zink, Deborah L.,Burgess, Bruce,Wang, Jun,Singh, Sheo B.
, p. 3648 - 3651 (2008)
Platensimycin and platencin are novel natural product antibiotics that inhibit bacterial growth by inhibiting fatty acid biosynthesis enzymes FabF and FabF/FabH, respectively. Continued search for the natural congeners for structure activity relationship studies led to the isolation of a congener which possesses all of the twenty carbons of diterpenoid unit, a potential biosynthetic intermediate of platensic acid unit of platensimycin. Isolation, structure, and activity of homoplatensimide A and biosynthetic relationship to platensimycin have been described.
Modulation of the rate, enantioselectivity, and substrate specificity of semisynthetic transaminases based on lipid binding proteins using site directed mutagenesis
Kuang, Hao,Davies, Ronald R.,Distefano, Mark D.
, p. 2055 - 2060 (1997)
Fatty acid binding proteins are a class of small 15 kDa proteins with a simple architecture that forms a large solvent sequestered cavity. In previous work, we demonstrated that reductive amination reactions could be performed in this cavity by covalent attachment of a pyridoxamine cofactor to the protein. Here, we report the results of experiments in which the position of pyridoxamine attachment has been varied by site directed mutagenesis. The conjugate IFABP-PX60 reacts at least 9.4-fold more rapidly than our original conjugate ALBP-PX, while IFABP-PX72 inverts the enantioselectivity of reactions (compared to ALBP-PX) and IFABP-PX104 displays very selective substrate specificity. These results indicate that site-directed mutagenesis can be used to tune the rate, enantioselectivity, and substrate specificity of semisynthetic transaminases based on fatty acid binding proteins.
Kinetic mechanism of asparagine synthetase from Vibrio cholerae
Fresquet, Vicente,Thoden, James B.,Holden, Hazel M.,Raushel, Frank M.
, p. 63 - 75 (2004)
Asparagine synthetase B (AsnB) catalyzes the formation of asparagine in an ATP-dependent reaction using glutamine or ammonia as a nitrogen source. To obtain a better understanding of the catalytic mechanism of this enzyme, we report the cloning, expression, and kinetic analysis of the glutamine- and ammonia-dependent activities of AsnB from Vibrio cholerae. Initial velocity, product inhibition, and dead-end inhibition studies were utilized in the construction of a model for the kinetic mechanism of the ammonia- and glutamine-dependent activities. The reaction sequence begins with the ordered addition of ATP and aspartate. Pyrophosphate is released, followed by the addition of ammonia and the release of asparagine and AMP. Glutamine is simultaneously hydrolyzed at a second site and the ammonia intermediate diffuses through an interdomain protein tunnel from the site of production to the site of utilization. The data were also consistent with the dead-end binding of asparagine to the glutamine binding site and PPi with free enzyme. The rate of hydrolysis of glutamine is largely independent of the activation of aspartate and thus the reaction rates at the two active sites are essentially uncoupled from one another.
Production and optimization of L-Glutaminase enzyme from hypocrea jecorina pure culture
Buelbuel, Dilara,Karakus, Emine
, p. 385 - 397 (2013)
L-Glutaminase (L-glutamine amidohydrolase, EC 3.5.1.2) is the important enzyme that catalyzes the deamination of L-glutamine to L-glutamic acid and ammonium ions. Recently, L-glutaminase has received much attention with respect to its therapeutic and industrial applications. It acts as a potent antileukemic agent and shows flavor-enhancing capacity in the production of fermented foods. Glutaminase activity is widely distributed in plants, animal tissues, and microorganisms, including bacteria, yeasts, and fungi. This study presents microbial production of glutaminase enzyme from Hypocrea jecorina pure culture and determination of optimum conditions and calculation of kinetic parameters of the produced enzyme. The optimum values were determined by using sa Nesslerization reaction for our produced glutaminase enzyme. The optimum pH value was determined as 8.0 and optimum temperature as 50°C for the glutaminase enzyme. The Km and Vmax values, the kinetic parameters, of enzyme produced from Hypocrea jecorina, pure culture were determined as 0.491 mM for Km and 13.86 U/L for Vmax by plotted Lineweaver-Burk graphing, respectively. The glutaminase enzyme from H. jecorina microorganism has very high thermal and storage stability.
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Shimo,K.,Wakamatsu,S.
, p. 3788 - 3790 (1961)
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Substrate specificity of prostate-specific membrane antigen
Anderson, Marc O.,Wu, Lisa Y.,Santiago, Nicholas M.,Moser, Jamie M.,Rowley, Jennifer A.,Bolstad, Erin S.D.,Berkman, Clifford E.
, p. 6678 - 6686 (2007)
A series of putative dipeptide substrates of prostate-specific membrane antigen (PSMA) was prepared that explored α- and β/γ-linked acidic residues at the P1 position and various chromophores at the P2 position, while keeping the P1′ residue constant as l-Glu. Four chromophores were examined, including 4-phenylazobenzoyl, 1-pyrenebutyryl, 9-anthracenylcarboxyl-γ-aminobutyryl, and 4-nitrophenylbutyryl. When evaluating these chromophores, it was found that a substrate containing 4-phenylazobenzoyl at the P2 position was consumed most efficiently. Substitution at the P1 position with acidic residues showed that only γ-linked l-Glu and d-Glu were recognized by the enzyme, with the former being more readily proteolyzed. Lastly, binding modes of endogenous substrates and our best synthetic substrate (4-phenylazobenzoyl-Glu-γ-Glu) were proposed by computational docking studies into an X-ray crystal structure of the PSMA extracellular domain.
Improved Synthesis of Caged Glutamate and Caging Each Functional Group
Guruge, Charitha,Ouedraogo, Yannick P.,Comitz, Richard Louis,Ma, Jingxuan,Losonczy, Attila,Nesnas, Nasri
, (2018)
Glutamate is an excitatory neurotransmitter that controls numerous pathways in the brain. Neuroscientists make use of photoremovable protecting groups, also known as cages, to release glutamate with precise spatial and temporal control. Various cage designs have been developed and amongst the most effective has been the nitroindolinyl caging of glutamate. We, hereby, report an improved synthesis of one of the current leading molecules of caged glutamate, 4-carboxymethoxy-5,7-dinitroindolinyl glutamate (CDNI-Glu), which possesses efficiencies with the highest reported quantum yield of at least 0.5. We present the shortest route, to date, for the synthesis of CDNI-Glu in 4 steps, with a total reaction time of 40 h and an overall yield of 20%. We also caged glutamate at the other two functional groups, thereby, introducing two new cage designs: α-CDNI-Glu and N-CDNI-Glu. We included a study of their photocleavage properties using UV-vis, NMR, as well as a physiology experiment of a two-photon uncaging of CDNI-Glu in acute hippocampal brain slices. The newly introduced cage designs may have the potential to minimize the interference that CDNI-Glu has with the GABAA receptor. We are broadly disseminating this to enable neuroscientists to use these photoactivatable tools.
Nitro versus hydroxamate in siderophores of pathogenic bacteria: Effect of missing hydroxylamine protection in malleobactin biosynthesis
Franke, Jakob,Ishida, Keishi,Ishida-Ito, Mie,Hertweck, Christian
, p. 8271 - 8275 (2013)
The elusive structure of malleobactin, a virulence factor of pathogens belonging to the Burkholderia mallei family, was finally unveiled by genetic and chemical analyses. The novel nitro-substituted siderophore is derived from an unusual, unprotected hydroxylamine, which undergoes spontaneous oxidation, as shown by in vitro assays and detection of analogues featuring hydroxylamino, nitroso, and azoxide groups. Copyright
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Talbot et al.
, p. 1440,1441 (1956)
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Comparative Study of Kinetic and Mechanistic Study of Oxidation of L-Alanine and L-Proline by Sodium Periodate Catalyzed by Osmium(VIII) in Micromolar Concentrations
Madhu Gupta,Srivastava, Amrita,Srivastava, Sheila
, p. 48 - 58 (2019)
Abstract: The kinetics of oxidation of two aliphatic α-amino acids (AA), namely, alanine and proline by NaIO4 has been investigated in alkaline medium in the presence of osmium(VIII) catalyst at a constant ionic strength of 1.0 mol dm–3 and at 25°C. The reactions were very slow to be measured in the absence of the catalyst. The reactions have a first order with respect both to [Os(VIII)] and [NaIO4], and fractional order with respect to both [L-alanine] (Ala) and [L-proline](Pro). The reaction show negligible effect of dielectric constant and ionic strength of medium. Increasing [OH–] concentration was found to decrease the oxidation rates while mercuric acetate acts as scavenger for both the reactions. A plausible oxidation mechanism has been proposed and the rate law expression has been derived. Both spectral and kinetic evidences revealed formation of intermediate complexes between AA and Os(VIII) before the rate-controlling step. Kinetic investigations have revealed that the order of reactivity is Pro > Ala. The complex thus formed reacts with the oxidant [NaIO4] by an inner-sphere mechanism with formation of the oxidation products of the amino acids which were identified as the corresponding carboxylic compounds, ammonium ion and carbon dioxide. The activation parameters of the first order rate constants were evaluated and discussed.
Photolabile Precursors of Biological Amides: Synthesis and Characterization of Caged o-Nitrobenzyl Derivatives of Glutamine, Asparagine, Glycinamide, and γ-Aminobutyramide
Ramesh, Doraiswamy,Wieboldt, Raymond,Billington, Andrew P.,Carpenter, Barry K.,Hess, George P.
, p. 4599 - 4605 (1993)
The synthesis and photochemical properties of o-nitrobenzyl derivatives of glutamine, asparagine, glycinamide, and γ-aminobutyramide (GABA amide) linked through the amide nitrogen are reported.The time scale for the release of the amides from the photolabile o-nitrobenzyl protecting group was unknown and has now been investigated.The compounds are photolyzed by UV irradiation at 308 and 350 nm to release free amino acid amide and the presumed aromatic nitroso side product, with quantum yields in the range of 0.13 for the methyl derivative of glutamine (20) to 0.24 for the carboxy derivative of glutamine (21).Both pH and the α-substituent of the o-nitrobenzyl protecting group affect the rate of the photolysis reaction which is initiated by a single laser pulse at 308 nm and monitored by the optical absorbance decay time course of the transient aci-nitro anion intermediate.The rate of disappearance of this intermediate, assumed to reflect the appearance of products, is influenced by pH and the α-substituent attached to the benzylic carbon.For example, the rates for the α-carboxyl (21) and α-H (19) derivatives of glutamine increase by a factor of 50 as the pH is lowered from 11.5 to 5.5, whereas the rate for the α-methyl derivative (20) shows a minimum at pH 9.5.The half lives of the aci-nitro intermediates of the α-methyl, α-carboxyl, and α-H derivatives of glutamine at pH 7.5 are 360, 720, and 1800 μs, respectively.
Structures and antitumor activities of ten new and twenty known surfactins from the deep-sea bacterium Limimaricola sp. SCSIO 53532
Chen, Min,Chen, Rouwen,Ding, Wenping,Li, Yanqun,Tian, Xinpeng,Yin, Hao,Zhang, Si
, (2022/01/11)
Surfactins are natural biosurfactants with myriad potential applications in the areas of healthcare and environment. However, surfactins were almost exclusively produced by the bacterium Bacillus species in previous reported literatures, together with difficulty in isolating pure monomer, which resulted in making extensive effort to remove duplication and little discovery of new surfactins in recent years. In the present study, the result of Molecular Networking indicated that Limimaricola sp. SCSIO 53532 might well be a potential resource for surfacin-like compounds based on OSMAC strategy. To search for new surfactins with significant biological activity, further study was undertaken on the strain. As a result, ten new surfactins (1–10), along with twenty known surfactins (11–30), were isolated from the ethyl acetate extract of SCSIO 53532. Their chemical structures were established by detailed 1D and 2D NMR spectroscopy, HRESIMS data, secondary ion mass spectrometry (MS/MS) analysis, and chemical degradation (Marfey's method) analysis. Cytotoxic activities of twenty-seven compounds against five human tumor cell lines were tested, and five compounds showed significant antitumor activities with IC50 values less than 10 μM. Furtherly, analysis of structure–activity relationships revealed that the branch of side chain, the esterification of Glu or Asp residue, and the amino acid residue of position 7 possessed a great influence on antitumor activity.
Isolation, Structure Determination, and Total Synthesis of Hoshinoamide C, an Antiparasitic Lipopeptide from the Marine Cyanobacterium Caldora penicillata
Iwasaki, Arihiro,Ohtomo, Keisuke,Kurisawa, Naoaki,Shiota, Ikuma,Rahmawati, Yulia,Jeelani, Ghulam,Nozaki, Tomoyoshi,Suenaga, Kiyotake
, p. 126 - 135 (2021/01/13)
Hoshinoamide C (1), an antiparasitic lipopeptide, was isolated from the marine cyanobacterium Caldora penicillata. Its planar structure was elucidated by spectral analyses, mainly 2D NMR, and the absolute configurations of the α-amino acid moieties were determined by degradation reactions followed by chiral-phase HPLC analyses. To clarify the absolute configuration of an unusual amino acid moiety, we synthesized two possible diastereomers of hoshinoamide C and determined its absolute configuration based on a comparison of their spectroscopic data with those of the natural compound. Hoshinoamide C (1) did not exhibit any cytotoxicity against HeLa or HL60 cells at 10 μM, but inhibited the growth of the parasites responsible for malaria (IC50 0.96 μM) and African sleeping sickness (IC50 2.9 μM).
Method for photolysis of amido bonds
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Paragraph 0046; 0048-0049; 0114-0117, (2021/06/26)
The invention discloses a method for photo-splitting amido bonds, wherein the method is mild in reaction condition and can realize splitting of amido bonds by using illumination. The method for photo-splitting the amido bonds comprises the following steps: reacting 2,4-dinitrofluorobenzene with an amino group of a substance which contains alpha amino acid at the tail end and is shown as a structural formula I to generate a compound 1 represented by a structural formula II; and under light irradiation, carrying out amido bond cleavage reaction on the compound 1, wherein R1 is a side chain group of alpha-amino acid, and R2 is aryl, aliphatic hydrocarbon, -CH(R)-COOH or polypeptide.
