- Enhancing effect of macroporous adsorption resin on gamma-aminobutyric acid production by Enterococcus faecium in whole-cell biotransformation system
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Gamma-aminobutyric acid (GABA) biosynthesis depended to a great extent on the biotransformation characterization of glutamate decarboxylase (GAD) and process conditions. In this paper, the enhancing effect of D101 macroporous adsorption resin (MAR) on the GABA production was investigated based on the whole-cell biotransformation characterization of Enterococcus faecium and adsorption characteristics of D101 MAR. The results indicated that the optimal pH for reaction activity of whole-cell GAD and pure GAD was 4.4 and 5.0, respectively, and the pH range retained at least 50% of GAD activity was from 4.8 to 5.6 and 4.0–4.8, respectively. No substrate inhibition effect was observed on both pure GAD and whole-cell GAD, and the maximum activity could be obtained when the initial L-glutamic acid (L-Glu) concentration exceeded 57.6?mmol/L and 96.0?mmol/L, respectively. Besides, GABA could significantly inhibit the activity of whole-cell GAD rather than pure GAD. When the initial GABA concentration of the reaction solution remained 100?mmol/L, 33.51 ± 9.11% of the whole-cell GAD activity was inhibited. D101 MAR exhibited excellent properties in stabilizing the pH of the conversion reaction system, supplementing free L-Glu and removing excess GABA. Comparison of the biotransformation only in acetate buffer, the GABA production, with 50?g/100?mL of D101 MAR, was significantly increased by 138.71 ± 5.73%. D101 MAR with pre-adsorbed L-Glu could significantly enhance the production of GABA by gradual replenishment of free L-Glu, removing GABA and maintaining the pH of the reaction system, which would eventually make the GABA production more economical and eco-friendly.
- Yang, Sheng-Yuan,Liu, Shu-Min,Jiang, Min,Wang, Biao-Shi,Peng, Luo-Hui,Zeng, Chan
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- Synthesis of the neurotransmitter 4-aminobutanoic acid (GABA) from diethyl cyanomalonate
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GABA was synthesized by deethoxycarbonylation, ester hydrolysis and nitrile reduction of a highly functionalized intermediate obtained by alkylation of diethyl cyanomalonate with ethyl bromoacetate. By judicious employment of D 2O or NaBD4 in one of the three functional group transformation steps, deuterium was selectively introduced into each of the three possible sites in GABA.
- Cook, Matthew C.,Witherell, Ross D.,White, Robert L.
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- Mechanistic aspects of uncatalyzed and ruthenium(III) catalyzed oxidation of DL-ornithine monohydrochloride by silver(III) periodate complex in aqueous alkaline medium
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The oxidation of an amino acid, DL-ornithine monohydrochloride (OMH) by diperiodatoargentate(III) (DPA) was carried out both in the absence and presence of ruthenium(III) catalyst in alkaline medium at 25°C and a constant ionic strength of 0.10 mol dm-3 spectrophorometrically. The reaction was of first order in both catalyzed and uncatalyzed cases, with respect to [DPA] and was less than unit order in [OMH] and negative fraction in [alkali]. The order with respect to [OMH] changes from first order to zero order as the [OMH] increases. The order with respect to Ru(III) was unity. The uncatalyzed reaction in alkaline medium has been shown to proceed via a DPA-OMH complex, which decomposes in a rate determining step to give the products. Where as in catalyzed reaction, it has been shown to proceed via a Ru(III)-OMH complex, which further reacts with two molecules of DPA in a rate determining step to give the products. The reaction constants involved in the different steps of the mechanisms were calculated for both the reactions. The catalytic constant (Kcat.const.) was also calculated for catalyzed reaction at different temperatures. The activation parameters with respect to slow step of the mechanism and also the thermodynamic quantities were determined.
- Malode, Shweta J.,Abbar, Jyothi C.,Nandibewoor, Sharanappa T.
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- Glutamate decarboxylase from Lactobacillus brevis: Activation by ammonium sulfate
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In this study, the glutamate decarboxylase (GAD) gene from Lactobacillus brevis IFO12005 (Biosci. Biotechnol. Biochem., 61, 1168-1171 (1997)), was cloned and expressed. The deduced amino acid sequence showed 99.6% and 53.1% identity with GAD of L. brevis ATCC367 and L. lactis respectively. The His-tagged recombinant GAD showed an optimum pH of 4.5-5.0, and 54 kDa on SDS-PAGE. The GAD activity and stability was significantly dependent on the ammonium sulfate concentration, as observed in authentic GAD. Gel filtration showed that the inactive form of the GAD was a dimer. In contrast, the ammonium sulfate-activated form was a tetramer. CD spectral analyses at pH 5.5 revealed that the structures of the tetramer and the dimer were similar. Treatment of the GAD with high concentrations of ammonium sulfate and subsequent dilution with sodium glutamate was essential for tetramer formation and its activation. Thus the biochemical properties of the GAD from L. brevis IFO12005 were significantly different from those from other sources.
- Hiraga, Kazumi,Ueno, Yoshie,Oda, Kohei
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- Lactams in sulfuric acid. The mechanism of amide hydrolysis in weak to moderately strong aqueous mineral acid media
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Reaction rate constants obtained in moderately concentrated sulfuric acid for the hydrolysis of simple lactams of ring sizes five, six, seven, and eight as a function of acidity and temperature have been analyzed using the excess acidity kinetic method. The basicity constants for these substrates have been recalculated; the 13C NMR spectra used to obtain these values are very sensitive to medium effects. It was found that the basicities of the lactams at 0.003-0.1 M lactam concentration were over half a pK unit more basic than they were at 0.5 M lactam, presumably because of the medium effect. Apart from this, the rate constant results obtained at different times by different groups using different techniques for monitoring the kinetics are in adequate agreement. The excess acidity analysis showed that the kinetics could be fitted according to the 'three-water-molecule followed by one-water-molecule' mechanistic scenario previously found, or could just as well be fitted by a 'one-water-molecule followed by unknown mechanism' scenario, with the mechanistic change taking place at 50 wt.% sulfuric acid for all the substrates. Other evidence makes the latter seem the more likely possibility of the two, and activation parameters based upon the 'one-water- molecule' process were determined. Sufficient data points to enable the unknown mechanism to be established were not present; possible mechanisms applicable in media more concentrated than 50 wt.% sulfuric acid are discussed. Previously obtained values of the parameter r, the number of water molecules involved with the substrate in A2 processes, are now questionable.
- Cox, Robin A.
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- Osmium(VIII) catalyzed oxidation of DL-ornithine monohydrochloride by a new oxidant, diperiodatoargentate(III) in aqueous alkaline medium
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The kinetics of osmium(VIII) (Os(VIII)) catalyzed oxidation of DL-ornithine monohydrochloride (OMH) by diperiodatoargentate(III) (DPA) in alkaline medium at 298 K and a constant ionic strength of 0.10 mol dm-3 was studied spectrophotometrically. The stoichiometry is, i.e., [OMH]:[DPA] [image omitted] 1:2. The main products were identified by spot tests, IR, 1H NMR, GC-MS spectral studies. A suitable mechanism is proposed. The reaction constants involved in the different steps of the mechanism are calculated. The catalytic constant (Kc) was also calculated for Os(VIII) catalysis at different temperatures. The active species of catalyst and oxidant have been identified. Copyright Taylor & Francis Group, LLC.
- Malode, Shweta J.,Abbar, Jyothi C.,Nandibewoor, Sharanappa T.
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- Augmentation of endogenous GABA pool size induced by Magainin II peptide
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Background: Gamma aminobutyric acid (GABA), an inhibitory neurotransmitter, is produced via decarboxylation of L-glutamate through the glutamic acid decarboxylase (GAD) enzyme. The synchronic action of GABA-transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH) enzymes convert the GABA metabolite into succinate. Given this background, our research was aimed at probing the effect of Magainin II, on the activity of GABA shunt metabolizing enzymes. Methods: Male NIH mice were administered peripherally by Magainin II (50 μg/kg body weight) and saline solution (%0.9 (w/v)) as the control vehicle. At different time intervals, the mice were sacrificed to evaluate the effect of Magainin II injection on the GABA shunt pathway. The activity of hypothalamic GAD, GABA-T and SSADH enzymes were determined using relevant enzyme assays. Results: Magainin II effectively enhanced the activity of GAD, by %90, 24 h after injection, while quenching the activities of GABA-T and SSADH by %43 and %71, respectively. In vitro models also revealed the direct but reversible interaction between the peptide and each of the individual enzymes of GABA shunt pathway. Conclusion: This study confirms the probable role of Magainin II in increasing the GABA content of the mouse hypothalamus. This property might candidate the peptide as a novel agent for improving the symptoms of many GABA dependent psychiatric disorders.
- Boostan, Nona,Yazdanparast, Razieh
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- Kinetic and mechanistic aspects of osmium(VIII) catalyzed oxidation of DLornithine by copper(iii) periodate complex in aqueous alkaline medium
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The oxidation of DL-ornithine monohydrochloride (OMH) by diperiodatocuprate(III) (DPC) has been investigated in the presence of osmium(VIII) catalyst in aqueous alkaline medium at a constant ionic strength of 0.20 mol dm-3 spectrophotometrically. The reaction exhibits 1:4 stoichiometry i.e., [OMH]: [DPC]. The order of the reaction with respect to [DPC] was unity while the order with respect to [OMH] was less than unity over the concentration range studied. The rate increased with an increase in [OH -] and decreased with an increase in [IO4-]. The order with respect to [Os(VIII)] was unity. The reaction rates revealed that Os(VIII) catalyzed reaction was about nine-fold faster than the uncatalyzed reaction. The oxidation products were identified by spectral analysis. Suitable mechanism has been proposed. The reaction constants involved in the different steps of the reaction mechanism were calculated. The catalytic constant (KC) was also calculated at different temperatures. The activation parameters with respect to slow step of the mechanism and also the thermodynamic quantities were determined. Kinetic experiments suggest that [OsO4(OH) 2]2- is the reactive Os(VIII) species and [Cu(H 2IO6)(H2O)2] is the reactive copper(III) species. by Oldenbourg Wissenschaftsverlag, Muenchen.
- Abbar, Jyothi C.,Malode, Shweta J.,Nandibewoor, Sharanappa T.
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- Characterization of glutamate decarboxylase from a high γ-aminobutyric acid (GABA)-producer, Lactobacillus paracasei
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γ-Aminobutyric acid (GABA) has several physiological functions in humans. We have reported that Lactobacillus paracasei NFRI 7415 produces high levels of GABA. To gain insight into the higher GABA-producing ability of this strain, we analyzed glutamate decarboxylase (GAD), which catalyzes the decarboxylation of L-glutamate to GABA. The molecular weight of the purified GAD was estimated to be 57 kDa by SDS-PAGE and 110 kDa by gel filtration, suggesting that GAD forms the dimer under native conditions. GAD activity was optimal at pH 5.0 at 50°C. The Km value for the catalysis of glutamate was 5.0 mM, and the maximum rate of catalysis was 7.5 μmol min-1 mg-1. The N-terminal amino acid sequence of GAD was determined, and the gene encoding GAD from genomic DNA was cloned. The findings suggest that the ability of Lb. paracasei to produce high levels of GABA results from two characteristics of GAD, viz., a low Km value and activity at low pH.
- Komatsuzaki, Noriko,Nakamura, Toshihide,Kimura, Toshinori,Shima, Jun
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- METHODS AND MATERIALS FOR ASSESSING AND TREATING OBESITY
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This document relates to methods and materials for assessing and/or treating obese mammals (e.g., obese humans). For example, methods and materials for using one or more interventions (e.g., one or more pharmacological interventions) to treat obesity and/or obesity-related comorbidities in a mammal (e.g., a human) identified as being likely to respond to a particular intervention (e.g., a pharmacological intervention) are provided.
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- An Integrated Cofactor/Co-Product Recycling Cascade for the Biosynthesis of Nylon Monomers from Cycloalkylamines
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We report a highly atom-efficient integrated cofactor/co-product recycling cascade employing cycloalkylamines as multifaceted starting materials for the synthesis of nylon building blocks. Reactions using E. coli whole cells as well as purified enzymes produced excellent conversions ranging from >80 and 95 % into desired ω-amino acids, respectively with varying substrate concentrations. The applicability of this tandem biocatalytic cascade was demonstrated to produce the corresponding lactams by employing engineered biocatalysts. For instance, ?-caprolactam, a valuable polymer building block was synthesized with 75 % conversion from 10 mM cyclohexylamine by employing whole-cell biocatalysts. This cascade could be an alternative for bio-based production of ω-amino acids and corresponding lactam compounds.
- Sarak, Sharad,Sung, Sihyong,Jeon, Hyunwoo,Patil, Mahesh D.,Khobragade, Taresh P.,Pagar, Amol D.,Dawson, Philip E.,Yun, Hyungdon
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p. 3481 - 3486
(2020/12/17)
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- METHODS FOR IMPROVING YIELDS OF L-GLUFOSINATE
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Compositions and methods for the production of L-glufosinate are provided. The method involves converting racemic glufosinate to the L-glufosinate enantiomer or converting PRO to L-glufosinate in an efficient manner. In particular, the method involves the specific amination of PRO to L-glufosinate, using L-glutamate, racemic glutamate, or another amine source as an amine donor. PRO can be obtained by the oxidative deamination of D-glufosinate to PRO (2- oxo-4-(hydroxy(methyl)phosphinoyl)butyric acid) or generated via chemical synthesis. PRO is then converted to L-glufosinate using a transaminase in the presence of an amine donor. When the amine donor donates an amine to PRO, L-glufosinate and a reaction by product are formed. Because the PRO remaining represents a yield loss of L-glufosinate, it is desirable to minimize the amount of PRO remaining in the reaction mixture. Degradation, other chemical modification, extraction, sequestration, binding, or other methods to reduce the effective concentration of the by-product, i.e., the corresponding alpha ketoacid or ketone to the chosen amine donor will shift the reaction equilibrium toward L-glufosinate, thereby reducing the amount of PRO and increasing the yield of L-glufosinate. Therefore, the methods described herein involve the conversion or elimination of the alpha ketoacid or ketone by-product to another product to shift the equilibrium towards L-glufosinate.
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(2020/03/29)
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- Intramolecular Hydrogen-Bonding Modulates the Nucleophilic Reactivity of Ammonium-Peroxycarboxylates
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The ammonium-peroxycarboxylic acid mesylates derived from γ-aminobutyric acid, β-alanine, and β-piperidinopropionic acid were synthesized and characterized by spectroscopic methods and X-ray crystallography. To study the nucleophilic reactivities of the corresponding ammonium- and amino-peroxycarboxylates, the kinetics of their reactions with a series of benzhydrylium ions (Ar2CH+) were investigated in alkaline, aqueous solutions at 20 °C. Using sequential-mixing stopped-flow UV/Vis photometry, the rates of the reactions of the short-lived nucleophiles with Ar2CH+ were determined and analyzed by the linear free energy relationship lg k = sN(N + E) furnishing nucleophilicity parameters (N, sN) of the peroxycarboxylates. Quantum chemical calculations indicate that the reactivity of the zwitterionic ammonium-peroxycarboxylates is attenuated by intramolecular N–H···O hydrogen bonding.
- Mayer, Robert J.,Ofial, Armin R.
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supporting information
p. 6010 - 6017
(2018/11/10)
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- Directed, regiocontrolled hydroamination of unactivated alkenes via protodepalladation
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A directed, regiocontrolled hydroamination of unactivated terminal and internal alkenes is reported. The reaction is catalyzed by palladium(II) acetate and is compatible with a variety of nitrogen nucleophiles. A removable bidentate directing group is used to control the regiochemistry, prevent β-hydride elimination, and stabilize the nucleopalladated intermediate, facilitating a protodepalladation event. This method affords highly functionalized amino acids in good yields with high regioselectivity.
- Gurak, John A.,Yang, Kin S.,Liu, Zhen,Engle, Keary M.
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supporting information
p. 5805 - 5808
(2016/06/09)
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- Two-photon sensitive protecting groups operating via intramolecular electron transfer: Uncaging of GABA and tryptophan
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Improved photo-labile protecting groups, with high sensitivity to two-photon excitation, are needed for the controlled release of drugs, as tools in neuroscience and physiology. Here we present a new modular approach to the design of caging groups based on photoinduced electron transfer from an electron-rich two-photon dye to an electron acceptor, followed by scission of an ester to release a carboxylic acid. Three different electron acceptors were tested: nitrobenzyl, phenacyl and pyridinium. The nitrobenzyl system was ineffective, giving only photochemical decomposition and no release of the carboxylic acid. The phenacyl system also performed poorly, liberating the carboxylic acid in 20% chemical yield and 0.2% photochemical yield. The pyridinium system was most successful, and was tested for the release of two carboxylic acids: γ-amino butyric acid (GABA) and tryptophan. The caged GABA undergoes photochemical cleavage with a chemical yield of >95% and a photochemical yield of 1%; it exhibits a two-photon absorption cross section of 1100 GM at 700 nm, corresponding to a two-photon uncaging cross section of 10 ± 3 GM. This journal is
- Korzycka, Karolina A.,Bennett, Philip M.,Cueto-Diaz, Eduardo Jose,Wicks, Geoffrey,Drobizhev, Mikhail,Blanchard-Desce, Mireille,Rebane, Aleksander,Anderson, Harry L.
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p. 2419 - 2426
(2015/03/30)
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- Design, synthesis, and potent antiepileptic activity with latent nerve rehabilitation of novel γ-aminobutyric acid derivatives
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We aimed to design and synthesize novel γ-aminobutyric acid (GABA) derivatives with the combination of aspirin (ASA) of nerve rehabilitative pharmacophores so as to develop multifunctional drugs useful in the treatment of neurological disorders. Twenty-four novel esters and amides of 1a were synthesized, biologically evaluated for antiepileptic activity with the model of 4-aminopyridine (4-AP), and tested for their capacity of penetrating the blood-brain barrier (BBB) with HPLC. The distribution of 8a, ASA freed by 8a, 7c, and ASA freed by 7c within 24 h in brain tissue was measured. The structure-activity relationship (SAR) was established and the data of Computer Aided Drug Design (CADD) showed good results. With ED50 values of, 0.3684-0.5199 mmol/kg, LD50 1.1487-1.3944 mmol/kg, and therapeutic index (TI) 2.65-3.15, compounds 8a, 3b, 4b, 6c, and 7c exhibited better antiepileptic activities in multiples of 0.3 to 2.2 against the control sodium valproate (VPA). Most importantly, 8a and 7c exhibited excellent antiepileptic activities with TI values of, 3.15 and 3.12, respectively.
- He, Dian,Ma, Jing,Shi, Xiuxiao,Zhao, Chunyan,Hou, Meng,Guo, Qingxin,Ma, Shangxian,Li, Xiaojun,Zhao, Peicheng,Liu, Wenhu,Yang, Zhuqing,Mou, Jianping,Song, Pengfei,Zhang, Yang,Li, Jing
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p. 967 - 978
(2015/02/19)
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- Immunomodulatory peptides
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The invention relates to peptides derivatized with a hydrophilic polymer which, in some embodiments, bind to human FcRn and inhibit binding of the Fc portion of an IgG to an FcRn, thereby modulating serum IgG levels. The disclosed compositions and methods may be used in some embodiments, for example, in treating autoimmune diseases and inflammatory disorders. The invention also relates, in further embodiments, to methods of using and methods of making the peptides of the invention.
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- Efficient one-step preparation of γ-aminobutyric acid from glucose without an exogenous cofactor by the designed Corynebacterium glutamicum
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Lactobacillus plantarum CCTCC M209102 efficiently produces γ-aminobutyric acid (GABA) from l-glutamate, in which glutamate decarboxylase and pyridoxal kinase are involved in the transformation. Pyridoxal kinase catalyzes ATP-dependent phosphorylation of pyridoxal to produce pyridoxal-5′-phosphate, which is the cofactor required for glutamate decarboxylase to biotransform GABA from l-glutamate. Corynebacterium glutamicum G01 is a good producer of l-glutamate from glucose. However, it cannot yield GABA from l-glutamate due to the absence of glutamate decarboxylase and pyridoxal kinase. In this work, to realize the efficient one-step preparation of GABA from glucose without exogenous pyridoxal-5′-phosphate, the metabolic module from L-glutamate to GABA based on glutamate decarboxylase and pyridoxal kinase in L. plantarum was grafted into C. glutamicum. To further improve the GABA production, the pathways to by-product pools of L-arginine, L-proline and L-lysine were blocked using the insertional mutation technique. The engineered C. glutamicum APLGGP carrying argB::tacgad, proB::tacgad and dapA::tacplk could efficiently convert glucose into GABA in one-step without an exogenous co-factor. In fed-batch cultures, the recombinant C. glutamicum APLGGP produced 70.6 g L-1 GABA at 30 °C and 70 h through a two-stage pH control strategy. To our knowledge, this is the highest reported GABA production using glucose as a substrate, and this designed C. glutamicum should be an excellent candidate for producing GABA on an industrial scale. This work is expected to pave the way to redesign the bioreactor for efficient one-step biosynthesis of GABA from glucose without an exogenous co-factor. the Partner Organisations 2014.
- Zhang, Rongzhen,Yang, Taowei,Rao, Zhiming,Sun, Hongmei,Xu, Meijuan,Zhang, Xian,Xu, Zhenghong,Yang, Shangtian
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p. 4190 - 4197
(2014/11/08)
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- Mechanism of cysteine-dependent inactivation of aspartate/glutamate/ cysteine sulfinic acid α-decarboxylases
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Animal aspartate decarboxylase (ADC), glutamate decarboxylase (GDC) and cysteine sulfinic acid decarboxylase (CSADC) catalyze the decarboxylation of aspartate, glutamate and cysteine sulfinic acid to β-alanine, γ-aminobutyric acid and hypotaurine, respectively. Each enzymatic product has been implicated in different physiological functions. These decarboxylases use pyridoxal 5-phosphate (PLP) as cofactor and share high sequence homology. Analysis of the activity of ADC in the presence of different amino determined that beta-alanine production from aspartate was diminished in the presence of cysteine. Comparative analysis established that cysteine also inhibited GDC and CSADC in a concentration-dependent manner. Spectral comparisons of free PLP and cysteine, together with ADC and cysteine, result in comparable spectral shifts. Such spectral shifts indicate that cysteine is able to enter the active site of the enzyme, interact with the PLP-lysine internal aldimine, form a cysteine-PLP aldimine and undergo intramolecular nucleophilic cyclization through its sulfhydryl group, leading to irreversible ADC inactivation. Cysteine is the building block for protein synthesis and a precursor of cysteine sulfinic acid that is the substrate of CSADC and therefore is present in many cells, but the presence of cysteine (at comparable concentrations to their natural substrates) apparently could severely inhibit ADC, CSADC and GDC activity. This raises an essential question as to how animal species prevent these enzymes from cysteine-mediated inactivation. Disorders of cysteine metabolism have been implicated in several neurodegenerative diseases. The results of our study should promote research in terms of mechanism by which animals maintain their cysteine homeostasis and possible relationship of cysteine-mediated GDC and CSADC inhibition in neurodegenerative disease development.
- Liu, Pingyang,Torrens-Spence, Michael P.,Ding, Haizhen,Christensen, Bruce M.,Li, Jianyong
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p. 391 - 404
(2013/07/27)
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- The donor-acceptor biphenyl platform: A versatile chromophore for the engineering of highly efficient two-photon sensitive photoremovable protecting groups
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Different photoremovable protecting groups in the o-nitrobenzyl, phenacyl, and 2-(o-nitrophenyl)propyl series with a donor-acceptor biphenyl backbone, known to display excellent two-photon absorption cross-sections, were investigated in order to develop efficient two-photon sensitive photoremovable protecting groups. The 2-(o-nitrophenyl)propyl series was a more versatile platform to increase the two-photon sensitivity of photoremovable protecting groups, leading to the p-alkoxy and p-bisalkylamino-4-nitro-[1,1′- biphenyl]-3-yl)propyl derivatives: PENB and EANBP respectively. Those two photoremovable protecting groups are to date the best caging groups for two-photon excitation at 800 and 740 nm respectively, offering attracting perspectives in chemical biology.
- Specht, Alexandre,Bolze, Frederic,Donato, Loic,Herbivo, Cyril,Charon, Sebastien,Warther, David,Gug, Sylvestre,Nicoud, Jean-Franois,Goeldner, Maurice
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scheme or table
p. 578 - 586
(2012/06/30)
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- Wavelength-orthogonal photolysis of neurotransmitters in vitro
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Irradiation of a mixture of 4-methoxyphenacyl-caged (S)-glutamate and 4,5-dimethoxy-2-nitrobenzyl-caged γ-amino butyric acid (GABA) on neurons, at ~260 nm, evokes selective photorelease of (S)-glutamate (Glu) whereas photolysis at 405 nm causes selective photorelease of GABA.
- Stanton-Humphreys, Megan N.,Taylor, Ruth D. T.,McDougall, Craig,Hart, Mike L.,Brown, C. Tom A.,Emptage, Nigel J.,Conway, Stuart J.
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supporting information; scheme or table
p. 657 - 659
(2012/02/02)
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- A high-throughput screening assay for amino acid decarboxylase activity
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The development of sensitive and easy-to-apply high-throughput screening methods is a common need in modern biocatalysis. With these powerful analytical tools in hands, chemists can easily assess enzyme libraries to identify either novel biocatalysts or improved mutants. Within biocatalysis, amino acid decarboxylases are gaining an increased importance, with several diverse applications ranging from the synthesis of bio-commodities to medical applications (e.g., synthesis of enzyme inhibitors at the level of L-DOPA decarboxylase). Herein, an efficient and simple analytical method for high-throughput screening of amino acid decarboxylase activity is reported. The method is valid for the discrimination of a broad range of amino acid/amine pairs such as L-tyrosine/tyramine, L-DOPA/dopamine, 5-hydroxy-L-tryptophan/ serotonin, L-histidine/histamine, L-serine/ethanolamine, L-tryptophan/ tryptamine, L-glutamic acid/GABA, and L-alanine/ethylamine. It has proven its versatility by using pure substrates, mixtures, or enzymatic reactions, both coming either from commercial enzymes or derived from cell-free (crude) extracts. The limit of detection was 13 μM for ethanolamine in the presence of 50 mM L-serine, while z′ values were in the range 0.75-0.93, indicating the suitability for high-throughput screening. Copyright
- Medici, Rosario,De Maria, Pablo Dominguez,Otten, Linda G.,Straathof, Adrie J. J.
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experimental part
p. 2369 - 2376
(2011/10/13)
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- Reduction of alkyl and aryl azides with sodium thiophosphate in aqueous solutions
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A simple aqueous method for the conversion of alkyl and aryl azides into the corresponding amines using trisodium thiophosphate is presented. Thiophosphate is converted into phosphate during these formal reduction processes.
- Norcliffe, Jennifer L.,Conway, Louis P.,Hodgson, David R.W.
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supporting information; body text
p. 2730 - 2732
(2011/06/19)
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- METHOD FOR THE VINYLATION OF AMIDES
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A process for preparing an N-vinyl compound by vinylating a compound having at least one nitrogen atom (referred to hereinafter as compound for short) with acetylene, wherein before the vinylation, the compound is reacted with an alkali metal hydroxide in a reaction zone andthe mean residence time of the alkali metal hydroxide and of the compound in the reaction zone is less than 6 minutes.
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(2010/10/19)
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- Structural and functional characterization of plant aminoaldehyde dehydrogenase from pisum sativum with a broad specificity for natural and synthetic aminoaldehydes
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Aminoaldehyde dehydrogenases (AMADHs, EC 1.2.1.19) belong to the large aldehyde dehydrogenase (ALDH) superfamily, namely, the ALDH9 family. They oxidize polyamine-derived ω-aminoaldehydes to the corresponding ω-amino acids. Here, we report the first X-ray structures of plant AMADHs: two isoenzymes, PsAMADH1 and PsAMADH2, from Pisum sativum in complex with β-nicotinamide adenine dinucleotide (NAD+) at 2.4 and 2.15 A resolution, respectively. Both recombinant proteins are dimeric and, similarly to other ALDHs, each monomer is composed of an oligomerization domain, a coenzyme binding domain and a catalytic domain. Each subunit binds NAD+ as a coenzyme, contains a solvent-accessible C-terminal peroxisomal targeting signal (type 1) and a cation bound in the cavity close to the NAD+ binding site. While the NAD+ binding mode is classical for PsAMADH2, that for PsAMADH1 is unusual among ALDHs. A glycerol molecule occupies the substrate binding site and mimics a bound substrate. Structural analysis and substrate specificity study of both isoenzymes in combination with data published previously on other ALDH9 family members show that the established categorization of such enzymes into distinct groups based on substrate specificity is no more appropriate, because many of them seem capable of oxidizing a large spectrum of aminoaldehyde substrates. PsAMADH1 and PsAMADH2 can oxidize N,N,N-trimethyl-4-aminobutyraldehyde into γ-butyrobetaine, which is the carnitine precursor in animal cells. This activity highly suggests that in addition to their contribution to the formation of compatible osmolytes such as glycine betaine, β-alanine betaine and γ-aminobutyric acid, AMADHs might participate in carnitine biosynthesis in plants.
- Tylichova, Martina,Kopecny, David,Morera, Solange,Briozzo, Pierre,Lenobel, Rene,Snegaroff, Jacques,Sebela, Marek
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experimental part
p. 870 - 882
(2011/04/24)
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- α-Carboxy-6-nitroveratryl: A photolabile protecting group for carboxylic acids
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(Figure presented) The synthesis of a new photolabile protecting group for carboxylic acids, α-carboxy-6-nitroveratryl (αCNV), is described. Bromide 3, prepared in four steps from 3,4-dimethoxyphenylacetic acid, was used to alkylate carboxylic acids under mild conditions in good yield. Palladium-catalyzed deallylation afforded the acids 4a-h, which underwent rapid and quantitative photolysis at wavelengths longer than 300 nm to liberate the carboxylic acid in good to quantitative yield. The rate of photolysis and quantum yield were determined to be 325 s-1 and 0.17.
- Russell, Alexander G.,Ragoussi, Maria-Eleni,Ramalho, Rui,Wharton, Christopher W.,Carteau, David,Bassani, Dario M.,Snaith, John S.
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supporting information; scheme or table
p. 4648 - 4651
(2010/09/14)
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- Conductometric method for the rapid characterization of the substrate specificity of amine-transaminases
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Amine-transaminases (ATAs, ω-transaminases, ω-TA) are PLP-dependent enzymes that catalyze amino group transfer reactions. In contrast to the widespread and wellknown amino acid-transaminases, ATAs are able to convert substrates lacking an a-carboxylic functional group. They have gained increased attention because of their potential for the asymmetric synthesis of optically active amines, which are frequently used as building blocks for the preparation of numerous pharmaceuticals. Having already introduced a fast kinetic assay based on the conversion of the model substrate α-methylbenzylamine for the characterization of the amino acceptor specificity, we now report on a kinetic conductivity assay for investigating the amino donor specificity of a given ATA. The course of an ATA-catalyzed reaction can be followed conductometrically since the conducting substrates, a positively charged amine and a negatively charged keto acid, are converted to nonconducting products, a noncharged ketone and a zwitterionic amino acid. The decrease of conductivity for the investigated reaction systems were determined to be 33-52 μS mM-1. In contrast to other ATA-assays previously described, with this approach all transamination reactions between any amine and any keto add can be monitored without the need for an additional enzyme or staining solutions. The assay was used for the characterization of a ATA from Rhodobacter sphaeroides, and the data obtained were in excellent agreement with gas chromatography analysis.
- Schaetzle, Sebastian,Hoehne, Matthias,Robins, Karen,Bornscheuer, Uwe T.
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body text
p. 2082 - 2086
(2010/08/20)
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- Purification and characterization of the first archaeal glutamate decarboxylase from Pyrococcus horikoshii
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Glutamate decarboxylase (GAD) from the archaeon Pyrococcus horikoshii was successfully expressed and purified, with the aim of developing a hyperthermostable GAD for industrial applications. Its biochemical properties were different from those reported for other GADs. The enzyme had broad substrate specificity, and its optimum pH and temperature were pH 8.0 and >97°C.
- Kim, Han-Woo,Kashima, Yasuhiro,Ishikawa, Kazuhiko,Yamano, Naoko
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body text
p. 224 - 227
(2009/06/18)
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- The application of glutamic acid α-decarboxylase for the valorization of glutamic acid
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Glutamic acid is an important constituent of waste streams from biofuels production. It is an interesting starting material for the synthesis of nitrogen containing bulk chemicals, thereby decreasing the dependency on fossil fuels. On the pathway from glutamic acid to a range of molecules, the decarboxylation of glutamic acid to γ-aminobutyric acid (GABA) is an important reaction. This reaction, catalyzed by the enzyme glutamic acid α-decarboxylase (GAD) was studied on a gram scale. In this study, GAD was immobilized on Eupergit and in calcium alginate and its operational stability was determined in a buffer free system, using various reactor configurations. Immobilization was shown to increase the GAD stability. The conditions for the highest GABA production per gram of enzyme were determined by extrapolation of enzyme stability data. At 30 °C in a fed batch process this results in an average volumetric productivity of 35 kg m-3 hr-1. The cost of using GAD immobilized in calcium alginate was estimated as €5 per metric ton of product. Furthermore it was shown that the cofactor pyridoxal-5′-phosphate (PLP) could be regenerated by the addition of a small amount of α-ketoglutaric acid to the reactor. In conclusion the application of immobilized GAD in a fed batch reactor was shown to be a scalable process for the industrial production of GABA from glutamic acid. The Royal Society of Chemistry 2009.
- Lammens, Tijs M.,De Biase, Daniela,Franssen, Maurice C. R.,Scott, Elinor L.,Sanders, Johan P. M.
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experimental part
p. 1562 - 1567
(2010/06/17)
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- Competing pathways in the photo-Favorskii rearrangement and release of esters: Studies on fluorinated p-hydroxyphenacyl-caged GABA and glutamate phototriggers
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(Chemical Equation Presented) Three new trifluoromethylated p-hydroxyphenacyl (pHP)-caged γ-aminobutyric acid (GABA) and glutamate (Glu) derivatives have been examined for their efficacy as photoremovable protecting groups in aqueous solution. Through the
- Stensrud, Kenneth,Noh, Jihyun,Kandler, Karl,Wirz, Jakob,Heger, Dominik,Givens, Richard S.
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scheme or table
p. 5219 - 5227
(2009/12/08)
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- Photoprocesses of molecules with 2-nitrobenzyl protecting groups and caged organic acids
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The 308 nm photoinduced formation of the nitroso product and the intermediacy of the aci-nitro form(s) were studied for a series of 2-nitrobenzyl alkyl and aryl esters (1a-4e) and bis-(nitrophenyl)methyl acetates (5a-6b) by time-resolved UV-vis spectroscopy. A triplet state appears as major transient, when 2-nitrobenzyl derivatives 1 are substituted by 4,5-dimethoxy (2) and 4,5-methylenedioxy (3/4) groups. This triplet of charge transfer character is, however, not part of the route via the aci-nitro into the 2-nitroso form. The activation energy and preexponential factor of the longest lifetime component (τaci), i.e. the major part of the aci-nitro decay, were determined. The carboxylic acids as leaving groups have rather small effects on τaci. An additional nitrated phenyl ring in α-position (5) leads generally to shorter τaci value. Otherwise, the photogeneration of nitroso products is similar. The quantum yield (Φd) varies only moderately with structure, the yield of the aci-nitro form and Φd are correlated and little affected by solvent properties.
- Bley, Filiz,Schaper, Klaus,Goerner, Helmut
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p. 162 - 171
(2008/09/18)
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- Synthesis and photocleavage of 7-[{Bis(carboxymethyl)amino}-coumarin-4-yl] methyl-caged neurotransmitters
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7-[{Bis(carboxymethyl)amino}coumarin-4-yl]methyl-caged neurotransmitters (glutamate and GABA) were synthesized. Both caged compounds showed sufficient stability in the dark, were water-soluble at pH 7.2 without using organic solvents, and exhibited relati
- Senda, Naoko,Momotake, Atsuya,Arai, Tatsuo
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experimental part
p. 2384 - 2388
(2009/09/08)
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- Clean and highly selective oxidation of alcohols by the Phl(OAc) 2/Mn(TPP)CN/lm catalytic system
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An efficient method for the oxidation of alcohols is presented. Using catalytic amounts of manganese porphyrin [Mn(TPP)CN] in combination with (diacetoxyiodo)benzene (Phl(OAc)2) allows the conversion of benzylic and primary aliphatic and aromatic alcohols into the corresponding aldehydes, and secondary alcohols to ketones as the sole products. This method provides a cost-effective and environmentally friendly oxidation procedure due to the utilisation of less toxic Phl(OAc)2 and biologically relevant manganese porphyrins. The amounts of the products (%) and the selectivities are very dependent upon the nature of the metalloporphyrin catalysts and also upon the electronic and steric properties of the starting alcohols.
- Karimipour, Gholam Reza,Shadegan, Hamid Asadpour,Ahmadpour, Roxana
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p. 252 - 256
(2008/02/08)
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- Design and synthesis of novel sulfonamide-containing bradykinin hB 2 receptor antagonists. 2. Synthesis and structure-activity relationships of α,α-cycloalkylglycine sulfonamides
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Recently we reported on the design and synthesis of a novel class of selective nonpeptide bradykinin (BK) B2 receptor antagonists (J. Med. Chem. 2006, 3602-3613). This work led to the discovery of MEN 15442, an antagonist with subnanomolar affinity for the human B2 receptor (hB2R), which also displayed significant and prolonged activity in vivo (for up to 210 min) against BK-induced bronchoconstriction in the guinea-pig at a dose of 300 nmol/kg (it), while demonstrating only a slight effect on BK-induced hypotension. Here we describe the further optimization of this series of compounds aimed at maximizing the effect on bronchoconstriction and minimizing the effect on hypotension, with a view to developing topically delivered drugs for airway diseases. The work led to the discovery of MEN 16132, a compound which, after intratracheal or aerosol administration, inhibited, in a dose-dependent manner, BK-induced bronchoconstricton in the airways, while showing minimal systemic activity. This compound was selected as a preclinical candidate for the topical treatment of airway diseases involving kinin B2 receptor stimulation.
- Fattori, Daniela,Rossi, Cristina,Fincham, Christopher I.,Caciagli, Valerio,Catrambone, Fernando,D'Andrea, Piero,Felicetti, Patrizia,Gensini, Martina,Marastoni, Elena,Nannicini, Rossano,Paris, Marielle,Terracciano, Rosa,Bressan, Alessandro,Giuliani, Sandro,Maggi, Carlo A.,Meini, Stefania,Valenti, Claudio,Quartara, Laura
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p. 550 - 565
(2007/10/03)
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- LACTIC ACID BACTERIA CULTURE OF MUNG BEAN AND THE PREPARATION METHOD OF THE SAME, AND THE COSMETIC COMPOSITION COMPRISING THE SAME
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Disclosed is a lactic acid bacteria culture of mung bean obtained by culturing lactic acid bacteria in a culture medium containing mung bean extract. The culture contains the mung bean extract and GABA (γ~ Aminobutyric acid), so that it exhibits effects of promoting collagen synthesis and alleviating inflammation. Accordingly, the cosmetic composition containing the culture can be usefully used as a cosmetic composition for promoting collagen biosynthesis, preventing or improving skin senescence, ant i- inflammatory and preventing or improving skin injury.
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Page/Page column 16
(2008/06/13)
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- Mechanism of oxidation of L-proline by aqueous alkaline diperiodatoargentate (III): Decarboxylation and dehydration
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The kinetics of oxidation L-proline by diperiodatoargentate (III) (DPA) in alkaline medium at a constant ionic strength of 0.50 mol dm-3 was studied spectrophotometrically. The reaction between DPA and L-proline in alkaline medium exhibits 1:2 stoichiometry (L-proline:DPA). The reaction shows first order in [DPA] and has less than unit order dependence each in both [L-proline] and [alkali]. The effect of added products have been investigated. A decrease in the dielectric constant of the medium decreases the rate of the reaction. The oxidation reaction in alkaline medium has been shown to proceed via a DPA-L-proline complex, which decomposes slowly in a rate determining step followed by a fast step to give the products. The main products were identified by spot test, IR and NMR studies. The reaction constants involved in the different steps of the mechanism are calculated. The activation parameters with respect to slow step of the mechanism are computed and discussed. The thermodynamic quantities are also determined. by Oldenbourg Wissenschaftsverlag, Muenchen.
- Seregar,Hiremath,Nandibewoor
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p. 615 - 629
(2008/02/07)
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- Synthesis, photophysical, photochemical and biological properties of caged GABA, 4-[[(2H-1-benzopyran-2-one-7-amino-4-methoxy) carbonyl] amino] butanoic acid
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The photorelease of a caged neurotransmitter can be used to investigate the function of neuronal circuits in tissues. We have designed and synthesized a stable, caged γ-aminobutyric acid (GABA) derivative, 4-[[(2H-l-benzopyran- 2-one-7-amino-4-methoxy)carbonyl]amino] butanoic acid (BC204), that releases the neurotransmitter in physiological medium when irradiated with UV light at 300-400 nm in PBS at pH 7.4. The release of GABA occurs with the formation of the major photoproduct, 7-amino-4-(hydroxymethyl)-2H-1-benzopyran-2-one, via a solvolytic photodegradation mechanism of the coumarin moiety and was confirmed by electrospray mass spectrometry/mass spectrometry (ESI MS/MS). BC204 is chemically stable and shows no intrinsic activity after many hours under physiological dark conditions. These properties suggest that BC204 is an excellent form of caged GABA that is well suited for long-term biological studies.
- Cuerten, Beate,Kullmann, Paul H. M.,Bier, Mark E.,Kandler, Karl,Schmidt, Brigitte F.
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p. 641 - 648
(2008/02/03)
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- 1-Acyl-7-nitroindoline derivatives, their preparation and their use as photocleavable precursors
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Photoreleasable compounds comprising a caging moiety linked to an effector moiety represented by structural formula (I) wherein R1is hydrogen; C1-10alkyl or substituted alkyl; O(CH2)n—Y; N(COZ)(CH2)mY; or N[(CH2)mY′[(CH2)NY]; R2and R3are independently selected from: hydrogen; C1-10alkyl or substituted alkyl; or R2and R3together are cycloalkyl; R4is hydrogen; C1-10alkyl or substituted alkyl; phenyl or substituted phenyl; (CH2)nY; or (CH2)mO(CH2)nY; wherein m and n are independently between 1 and 10; Y and Y′ are independently selected from hydrogen, CO2H or salts thereof or OPO32?, Z is hydrogen or C1-10alkyl or substituted alkyl; and, X is an effector moiety or a group capable of being coupled or converted to an effector moiety, which are capable of releasing the effector moiety on irradiation, typically by flash irradiation with UV light. The photoreleasable compounds can therefor be used to deliver biologically active effector moieties such as neuroactive amino acids or metal chelators to sites where their activity is required.
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Page column 13
(2010/02/07)
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- Method of introducing amino group and method of synthesizing amino acid compound
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The present invention relates to a method for introducing an amino group into an organic acid or an organic ester by reacting an organic salt or an organic ester and ammonia under high-temperature and high-pressure water conditions, a method for synthesizing an amino acid or an amino ester by the above method, and a method for manufacturing an amino acid compound by synthesizing an amino acid or an amino ester by the above method and separating and refining it with an ion exchange resin.
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- Kinetics and Mechanism of Oxidative Degradation of L-Proline by Alkaline Diperiodatonickelate(IV) - A Free Radical Intervention and Decarboxylation
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The kinetics of oxidation of L-proline by diperiodatonickelate(IV) (DPN) in aqueous alkaline medium at a constant ionic strength of 0.50 mol dm -3 was studied spectrophotometrically. The reaction is of first order in [DPN], zero order in [alkali] and less than unit order in [L-proline]. Addition of periodate has no effect on the rate of reaction. Effect of added products, ionic strength and dielectric constant of the reaction medium have been investigated. The main products were identified by spot test and IR spectra. A mechanism involving the diperiodatonickelate(IV) (DPN) as the reactive species of the oxidant has been proposed. The reaction constants involved in the different steps of mechanism are calculated. The activation parameters with respect to slow step of the mechanism are computed and discussed and thermodynamic quantities are also calculated. The isokinetic temperature was determined and discussed.
- Mulla,Gurubasavaraj,Nandibewoor
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p. 1833 - 1840
(2007/10/03)
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- Schiff's Bases Formed between Pyridoxal 5'-Phosphate and 4-Aminobutanoic Acid. Kinetic and Thermodynamic Study
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The overall and individual kinetic constants of formation (k1 and k1i) and hydrolysis (k2, kOH and k2i) of the Schiff's bases formed between pyridoxal 5'-phosphate (PLP) and 4-aminobutanoic acid (GABA) at 10, 20, 25, 30, and 37 deg C, a variable pH and a constant ionic strength of 0.1 M (1 M = 1 mol dm-3) were determined. The formation of a Schiff's base is an intramolecular acid-catalyzed process. The activation and thermodynamic parameters for the formation and hydrolysis of the Schiff's bases were also determined. ΔH and ΔS for the individual processes were all found to be negative.
- Gorostidi, Gerardo R. Echevarria,Castellanos, M. Gabriela,Perez, Piedad Martin,Santos, Jose G.,Blanco, Francisco Garcia
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p. 523 - 528
(2007/10/03)
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- One-pot sequence for the decarboxylation of α-amino acids
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Treatment of an α-amino acid with N-bromosuccinimide in water at pH 5 or in an alcoholic-aqueous ammonium chloride mixture, followed by addition of nickel(II) chloride and sodium borohydride, effected an overall decarboxylation via an intermediate nitrile to afford the corresponding amine in good yield.
- Laval, Gilles,Golding, Bernard T.
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p. 542 - 546
(2007/10/03)
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- Method for producing carboxylic acid by alcohol oxidation
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The invention relates to a method for oxidizing primary amino alcohols, primary or secondary alkenols or alkinols into the corresponding acids or ketones. According to said method, a primary amino alcohol or a primary or secondary alkenol or alkinol is oxidized in the form of a substrate, in the presence of an equimolar quantity of periodate or a molar excess thereof in relation to the alcoholic hydroxy groups and catalytic quantities of dichromate or CrO3 and in the presence of an acid in water, a water/solvent mixture or a solvent at a temperature of ?20 ° C. to +50 ° C., to produce the corresponding acid or the corresponding ketone.
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- Use of GABA and GABAB agonists
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The present invention provides methods of stimulating tissue growth, including islet cell growth, by administering GABA or a GABA agonist to act on GABAB receptors and GABAB-like receptors to activate cell replication.
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- 2-aminopyridine derivatives and combinatorial libraries thereof
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The present invention relates to novel 2-aminopyridine derivative compounds of the following formula: wherein R1to R5have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminopyridine derivative compounds.
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- Composition of matter having bioactive properties
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Particles of coordinated complex comprising a basic, hydrous polymer and a capacitance adding compound, as well as methods for their production, are described. These complexes exhibit a high degree of bioactivity making them suitable for a broad range of applications through their incorporation into conventional vehicles benefiting from antimicrobial and similar properties.
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- New Phototriggers: Extending the p-Hydroxyphenacyl π-π* Absorption Range
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(Matrix Presented) Introducing 3-methoxy or 3,5-dimethoxy substituents on the 4-hydroxyphenacyl (pHP) photoremovable protecting group has been explored with two excitatory γ-amino acids, L-glutamic acid and γ-amino butyric acid (GABA). These substituents significantly extend the absorption range of the pHP chromophore, e.g., the tail of absorption bands of 2a,b extend above 400 nm, well beyond the absorptions of aromatic amino acids and nucleotides. Irradiation releases the amino acids with rate constants of ~107 s-1 and appearance efficiencies (Φapp) of 0.03-0.04. The photoproducts are formed through the pHP excited triplet and are primarily products of photoreduction and photohydrolysis. 1a,b also rearranged to the phenylacetic acid 3.
- Conrad II, Peter G.,Givens, Richard S.,Weber, J?rg F. W.,Kandler, Karl
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p. 1545 - 1547
(2007/10/03)
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- Artificial trinuclear metallopeptidase synthesized by cross-linkage of a molecular bowl with a polystyrene derivative
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A novel methodology is reported for construction of active sites of artificial multinuclear metalloenzymes: Transfer of metal-chelating sites confined in a prebuilt cage to a polymeric backbone. Artificial active sites comprising two or three moieties of Cu(II) complex of tris(2-aminoethyl)amine (tren) were prepared by transfer of Cu(II)tren units confined in a molecular bowl (MB) to poly(chloromethylstyrene-co-divinylbenzene) (PCD). By treatment of unreacted chloro groups of the resulting PCD with methoxide and destruction of the MB moieties attached to PCD with acid followed by addition of Cu(II) ion to the exposed tren moieties, catalytic polymers with peptidase activity were obtained. The average number (β) of proximal Cu(II)tren moieties in the active site of the artificial multinuclear metallopeptidase was determined by quantifying the Cu(II) content. Several species of the artificial metallopeptidases with different β contents were prepared and examined for catalytic activity in hydrolysis of various cinnamoyl amide derivatives. The PCD-based catalytic polymers did not hydrolyze a neutral amide but effectively hydrolyzed carboxyl-containing amides (N-cinnamoyl glycine, N-cinnamoyl β-alanine, and N-cinnamoyl γ-amino butyrate). Analysis of the kinetic data revealed that the active sites comprising three Cu(II)tren units were mainly responsible for the catalytic activity. When analyzed in terms of k(cat), the catalytic activity of the PCD-based artificial peptidase was comparable to or better than the catalytic antibody with the highest peptidase activity reported to date. A mechanism is suggested for the effective cooperation among the three metal centers of the active site in hydrolysis of the carboxyl-containing amides.
- Moon, Sung-Ju,Jeon, Joong Won,Kim, Heesuk,Suh, Myunghyun Paik,Sun, Junghun
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p. 7742 - 7749
(2007/10/03)
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- Use of GABAB receptor agonists as reflux inhibitors
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PCT No. PCT/SE97/01555 Sec. 371 Date Nov. 12, 1997 Sec. 102(e) Date Nov. 12, 1997 PCT Filed Sep. 15, 1997 PCT Pub. No. WO98/11885 PCT Pub. Date Mar. 26, 1998The present invention relates to the use of GABAB receptor agonists for the inhibition of transient lower esophageal sphincter relaxations, and for the treatment of gastro-esophageal reflux disease.
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