Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:6893-26-1 (glutamate)
 73,096 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-Alkoxycarbonylaminodicarboxylic acids were reacted in dichloromethane with N-ethyl-N'-(dimethylaminopropyl)carbodiimide hydrochloride, and with methyl chloroformate in the presence of N-methylmorpholine. Removal of secondary products by washing the mixtures with aqueous solutions gave good yields of the pure crystalline internal anhydrides. Anhydrides of N-benzyloxycarbonyl- (Z) and N-9-fluorenylmethoxycarbonyl-(Fmoc) L-glutamic and L-aspartic acids and of N-tert.-butoxycarbonyl-L-aspartic acid were prepared in this way. The compounds were shown to be amenable to normal phase high-performance liquid chromatography (NP-HPLC) on a CN-column using tert.-butanol-hexane as solvent. The products of the reactions of Z- and Fmoc-glutamic acid with hot acetic anhydride were examined by nuclear magnetic resonance and NP-HPLC before and after methanolysis in an attempt to establish if any of the corresponding pyroglutamates were formed. The reaction of Fmoc-chloride with Fmoc-glutamate was examined for the same reason. It is concluded that the side product generated during the reaction of Fmoc-chloride with glutamic acid which is used for analysis of the latter is the N-protected internal anhydride and not the pyroglutamate as reported in the literature.
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PMID:N-alkoxycarbonyl-glutamic and aspartic acids. Studies on the activation and cyclodehydration and side-reaction encountered in analysis of glutamic acid using Fmoc-chloride. 135 49

Buthionine sulfoximine inhibits gamma-glutamylcysteine synthetase, the enzyme catalyzing the first reaction of glutathione (GSH) biosynthesis. GSH synthesis is blocked in animals or cultured cells exposed to buthionine sulfoximine, and GSH is substantially depleted in cells or tissues with moderate to high rates of GSH utilization. Studies reported to date have used DL-buthionine (SR)-sulfoximine or L-buthionine (SR)-sulfoximine, mixtures of four and two isomers, respectively. The present report describes a chiral solvent HPLC procedure for the analytical separation of the diastereomers of L-buthionine (SR)-sulfoximine and the separation of those isomers from the unresolved diastereomers of D-buthionine (SR)-sulfoximine. L-buthionine (R)-sulfoximine was isolated preparatively by repeated crystallization of L-buthionine (SR)-sulfoximine from water; L-buthionine (S)-sulfoximine was obtained by crystallization as the trifluoroacetate salt in ethanol/hexane mixtures. The absolute configuration, bond lengths and angles of L-buthionine (R)-sulfoximine were determined by X-ray diffraction. In vitro studies demonstrate that L-buthionine (R)-sulfoximine is a relatively weak inhibitor of rat kidney gamma-glutamylcysteine synthetase; binding is competitive with L-glutamate. L-buthionine (S)-sulfoximine is a tight-binding, mechanism-based inhibitor of the enzyme. Since L-buthionine sulfoximine is initially bound as a transition-state analogue, identification of the inhibitory diastereomer elucidates the steric relationships among ATP, glutamate, and cysteine within the active site. When administered to mice, L-buthionine (S)-sulfoximine (0.2 mmol/kg) was as effective as L-buthionine (SR)-sulfoximine (0.4 mmol/kg) in causing GSH depletion in liver, kidney, and pancreas. L-Buthionine (R)-sulfoximine (0.2 mmol/kg) did not cause significant GSH depletion in liver or pancreas. The L-(R)-diastereomer caused a modest GSH depletion in kidney that is tentatively attributed to interference with gamma-glutamylcyst(e)ine transport.
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PMID:Analytical and preparative separation of the diastereomers of L-buthionine (SR)-sulfoximine, a potent inhibitor of glutathione biosynthesis. 167 99

The glutamate blocking action of 5-methyl-1-phenyl-2-(3-piperidinopropylamino)-hexane-1-ol (MLV-5860) was studied at the crayfish neuromuscular junction using electrophysiological techniques. The opener muscle of the dactyl in the first leg of the crayfish was used to examine the action of the drug on the glutamate response. MLV-5860 reduced the amplitude of repetitively-induced glutamate potentials in a dose-dependent manner at the crayfish neuromuscular junction and this reduction was time- and activity-dependent. The minimum effective concentration of MLV-5860 to reduce the glutamate response was estimated to be lower than 50 nM, and therefore MLV-5860 is the most powerful glutamate blocker known at the crayfish neuromuscular junction. Pretreatment of the muscle fiber with concanavalin A did not affect the action of MLV-5860. MLV-5860 reduced the amplitude of excitatory junctional potentials (EJPs) and increased the decay rate of extracellularly-recorded EJPs in a dose-dependent manner. Quisqualate responses were also reduced by this drug but the conductance increase of the muscle membrane induced by GABA was not affected. MLV-5860 did not cause a significant change in the input resistance of the opener muscle fiber at concentrations less than 10 microM. The action of the drug is possibly explained in part by the open channel block of the glutamate-activated ion channels. The forward rate constant for channel blockade was estimated from the difference between the decay rate constants of extracellular EJPs in the absence and presence of the drug and the estimated value was 6.5 +/- 1.4 X 10(7) M-1 s-1.
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PMID:A new potent channel blocker: effects on glutamate responses at the crayfish neuromuscular junction. 242 94

n-Hexane on coupled rabbit heart mitochondria induces "in vitro" uncoupling with both glutamate and succinate as substrates and the effect increases with increasing n-alkane concentration (from 0 to 160 microgram/mg mitochondrial protein) and temperature (from 15 degrees to 38 degrees C). The inner mitochondrial membrane is made permeable to proteins; moreover extrusion of some matrix enzymes and entry of exogenous NADH is produced. Furthermore at higher concentrations and temperatures NADH oxidase inhibition and increase of its thermosensitivity is shown whereas upon succinate oxidase is evidenced a biphasic effect (activation followed by inhibition). The results, qualitatively similar to those observed with detergents and solvents, suggest a fluidization of the lipid phase of the membrane.
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PMID:[Interaction of n-alkanes with respiration and oxidative phosphorylation in rabbit heart mitochondria: n-hexane]. 611 66

Studies "in vitro" on the effect of n-nonane on coupled rabbit heart mitochondria with both succinate and glutamate as substrates show that the hydrocarbon examined makes the membrane permeable to protons (uncoupling), to some matrix enzymes and to exogenous NADH. The effect increases with increasing n-alkane concentration (from 0 to 160 microgram/mg mitochondrial protein) and temperature (from 15 degrees to 38 degrees C). Furthermore at higher concentrations and temperatures NADH oxidase inhibition is observed, whereas on succinate oxidase a biphasic effect (activation at lower concentrations and inhibition at higher concentrations) is produced. However the results, qualitatively similar to those observed with n-hexane, exhibit features probably due to a longer chain and that can be ascribed to perturbations of the physical state of membrane lipids.
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PMID:[Interaction of n-alkanes with respiration and oxidative phosphorylation in rabbit heart mitochondria: n-nonane]. 611 67

The effect of n-dodecane, n-pentadecane and n-octadecane at various concentrations (from 0 to 160 microgram/mg mitochondrial protein) and temperatures (from 15 degrees to 38 degrees C) is studied "in vitro" on coupled rabbit heart mitochondria. With both glutamate and succinate as substrates, and at higher temperatures only, n-dodecane makes the membrane permeable to protons (uncoupling), to some matrix enzymes and poorly to NADH; moreover it slightly inhibits NADH-oxidase and exerts a biphasic action (activation followed by inhibition) on succinate oxidase. The results, qualitatively similar to those observed with n-hexane and n-nonane, are yet less striking and exhibit features probably due to the longer chain. The other n-alkanes examined do not show any effect.
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PMID:[Interaction of n-alkanes with respiration and oxidative phosphorylation in rabbit heart mitochondria: n-dodecane, n-pentadecane and n-octadecane]. 611 68

Toluene oxidation activity in Pseudomonas mendocina KR1 and Pseudomonas sp. strain ENVPC5 was induced by trichloroethylene (TCE), and induction was followed by the degradation of TCE. Higher levels of toluene oxidation activity were achieved in the presence of a supplemental growth substrate such as glutamate, with levels of activity of up to 86% of that observed with toluene-induced cells. Activity in P. mendocina KR1 was also induced by cis-1,2-dichloroethylene, perchloroethylene, chloroethane, hexane, pentane, and octane, but not by trans-1,2-dichloroethylene. Toluene oxidation was not induced by TCE in Burkholderia (Pseudomonas) cepacia G4, P. putida F1, Pseudomonas sp. strain ENV110, or Pseudomonas sp. strain ENV113.
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PMID:Induction of toluene oxidation activity in Pseudomonas mendocina KR1 and Pseudomonas sp. strain ENVPC5 by chlorinated solvents and alkanes. 757 58

2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (9) was designed as a conformationally constrained analog of glutamic acid. For 9, the key torsion angles (tau 1 and tau 2) which determine the relative positions of the alpha-amino acid and distal carboxyl functionalities are constrained where tau 1 = 166.9 degrees or 202 degrees and tau 2 = 156 degrees, respectively. We hypothesized that 9 would closely approximate the proposed bioactive conformation of glutamate when acting at group 2 metabotropic glutamate receptors (mGluRs). The racemic target molecule (+/-)-9, its C2-diastereomer (+/-)-16, and its enantiomers (+)-9 (LY354740) and (-)-9 (LY366563) were prepared by an efficient, stereocontrolled, and high-yielding synthesis from 2-cyclopentenone. Our hypothesis that 9 could interact with high affinity and specificity at group 2 mGluRs has been supported by the observation that (+/-)-9 (EC50 = 0.086 +/- 0.025 microM) and its enantiomer (+)-9 (EC50 = 0.055 +/- 0.017 microM) are highly potent agonists for group 2 mGluRs in the rat cerebral cortical slice preparation (suppression of forskolin-stimulated cAMP formation) possessing no activity at other glutamate receptor sites (iGluR or group 1 mGluR) at concentrations up to 100 microM. Importantly, the mGluR agonist effects of (+)-9 are evident following oral administration in mice in both the elevated plus maze model of anxiety (ED50 = 0.5 mg/kg) and in the ACPD-induced limbic seizure model (ED50 = 45.6 mg/kg). Thus, (+)-9 is the first orally active group 2 mGluR agonist described thus far and is an important tool for studying the effects of compounds of this class in humans.
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PMID:Design, synthesis, and pharmacological characterization of (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740): a potent, selective, and orally active group 2 metabotropic glutamate receptor agonist possessing anticonvulsant and anxiolytic properties. 904 44

3,5-Dihydroxyphenylglycine (DHPG), (S)-3-hydroxyphenylglycine and (S)-4-carboxy-3-hydroxyphenylglycine (S-4C3HPG) stimulated phosphoinositide hydrolysis in neonatal rat cortical slices, but with lower maximal effect, in comparison with 2S,1'S,2'S-2-(2'-carboxycyclopropyl)glycine (L-CCG I) or (1S,3R)-1-aminocyclo-pentane-1,3-dicarboxylic acid (1S,3R-ACPD). DHPG, 1S,3R-ACPD, and S-4C3HPG also evoked a rapidly desensitizing increase in [Ca2+]i in cortical layers of neonatal brain slices. (R,S)-alpha-methyl-4-tetrazolyl-phenylglycine (MTPG), and (R,S)-alpha-methyl-4-phosphono-phenylglycine (MPPG) inhibited the increase of phosphoinositide hydrolysis elicited by 1S,3R-ACPD but not that by R,S-DHPG. In contrast, the selective group II receptor agonist (1S,2S,5R,6S)-2-amino-bicyclo-[3.1.0]-hexane-2,6-dicarboxylate (LY 354740) potentiated the response of R,S-DHPG. Finally, 8-(4-chlorophenylthio)-cAMP, a membrane permeant analogue of cAMP, reversed the stimulatory effect of 1S,3R-ACPD and S-4C3HPG on phosphoinositide hydrolysis and [Ca2+]i mobilization, without affecting the response induced by R,S-DHPG. These data suggest that, in neonatal rat cortex, the activation of group II metabotropic glutamate receptors potentiates the phosphoinositide hydrolysis and [Ca2+]i responses mediated by group I metabotropic glutamate receptors.
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PMID:Involvement of a cyclic-AMP pathway in group I metabotropic glutamate receptor responses in neonatal rat cortex. 936 60

1. The binding of the new selective group II metabotropic glutamate receptor radioligand, [3H]-(2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine ([3H]-DCG IV), was characterized in rat mGlu2 receptor-transfected CHO cell membranes. 2. [3H]-DCG IV binding was pH-dependent, but was not sensitive to temperature. Saturation analysis showed the presence of a single binding site, with a Kd value of 160 nM and a Bmax value of 10 pmol mg(-1) protein. Binding was not sensitive to Na+-dependent glutamate uptake blockers or Cl-dependent glutamate binding inhibitors. Furthermore, up to concentrations of 1 mM, the glutamate ionotropic receptor agonists, N-methyl-D-aspartic acid (NMDA), (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate, did not affect [3H]-DCG IV binding. 3. Of the compounds observed to inhibit [3H]-DCG IV binding, the most potent were the recently described selective group II agonist, (+)-2-aminobicyclo-[3.1.0]hexane-2,6-dicarboxylate (LY 354740; Ki value 16 nM) and antagonist, 2-amino-2-(2-carboxycyclopropan-1-yl)-3-(dibenzopyran-4-yl) propanoic acid (LY 341495; Ki value 19 nM). As expected, for a G-protein-coupled receptor, guanosine-5'-O-(3-thiotriphosphate) (GTPgammaS) inhibited [3H]-DCG IV binding in a concentration-dependent manner, with an IC50 value of 12 nNM. 4. A highly significant correlation was observed between the potencies of compounds able to inhibit [3H]-DCG IV binding and potencies obtained for agonist activity in a GTPgamma35S binding functional assay. In addition, these studies identified a number of compounds with previously unknown activity at mGlu2 receptors, including L(+)-2-amino-3-phosphonopropionic acid (L-AP3), L(+)-2-amino-5-phosphonopentanoic acid (L-AP5), 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (R-CPP), N-acetyl-L-aspartyl-L-glutamic acid (NAAG) and (RS)-alpha-methylserine-O-phosphate (MSOP).
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PMID:Characterization of [3H]-(2S,2'R,3'R)-2-(2',3'-dicarboxy-cyclopropyl)glycine ([3H]-DCG IV) binding to metabotropic mGlu2 receptor-transfected cell membranes. 950 91


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