Disease relevance of 5-amino-5-carboxy-2-hydroxy-pent-1-ene-1-diazonium

• The combined actions of succinylated Acinetobacter glutaminase-asparaginase and 6-diazo-5-oxo-L-norleucine or Acivicin produced synergistic inhibition of nucleic acid synthesis in P388 tumor cells [1].
• Mouse P388 and L1210 leukemia cells grown in vitro were found to be 4 to 10 times more sensitive to 6-diazo-5-oxo-L-norleucine and 3 to 5 times more sensitive to Acivicin than were 3T3 and C57BL x DBA/2 F1 embryonic fibroblasts [1].
• The uptake system for 6-diazo-5-oxo-L-norleucine (DON) was studied in mouse P388 leukemia cells [2].
• Antiviral effect of 6-diazo-5-oxo-L-norleucine, antagonist of gamma-glutamyl transpeptidase, on replication of human parainfluenza virus type 2 [3].
• The toxicity of the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON) administered as a 24 hour infusion has been evaluated [4].

High impact information on 5-amino-5-carboxy-2-hydroxy-pent-1-ene-1-diazonium

• The CTP synthetase inhibitors 6-diazo-5-oxo-l-norleucine (DON) and alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) reduced the parasite CTP levels even further and inhibited trypanosome proliferation in vitro and in T. brucei-infected mice [5].
• This and other findings suggest that the norleucylglycine derivative was hydrolyzed by peptidase(s) bound to the outer surface of the brush border membranes and that the 6-diazo-5-oxo-L-norleucine thus released acts as an affinity-labeling reagent for the membrane-bound transferase [6].
• Glutamine oxidation was inhibited by prior incubation of the mitochondria with 6-diazo-5-oxo-L-norleucine, which inhibited mitochondrial glutaminase [7].
• The chemotherapeutic effects of 6-diazo-5-oxo-L-norleucine (DON) and N-[N-gamma-glutamyl-6-diazo-5-oxo-norleucinyl]6-diazo-5-oxo-norleucine (azotomycin) were evaluated in a spectrum of transplantable experimental tumor systems including xenografts of human tumors in athymic mice [8].
• Incubation of embryonic chick chondrocytes with 6-diazo-5-oxo-L-norleucine (DON), a glutamine analogue, led to a dose-dependent inhibition of [35S]sulfate incorporation into proteoglycan [9].

Chemical compound and disease context of 5-amino-5-carboxy-2-hydroxy-pent-1-ene-1-diazonium

• Phase II trial of 6-diazo-5-oxo-L-norleucine versus aclacinomycin-A in advanced sarcomas and mesotheliomas [10].
• Mutagenicity of D- and L-azaserine, 6-diazo-5-oxo-L-norleucine and N-(N-methyl-N-nitroso-carbamyl)-L-ornithine in the Salmonella test system [11].
• Poliovirus and vesicular stomatitis virus replication in the presence of 6-diazo-5-oxo-L-norleucine or 2-deoxy-D-glucose [12].
• The effects of 6-diazo-5-oxo-L-norleucine (DON), 2-deoxy-D-glucose (DOG), and tunicamycin (TM) on the replication of poliovirus (PV) and vesicular stomatitis virus (VSV) were examined [12].
• The diazo antibiotic 6 diazo-5-oxo-L-norleucine is transported into Escherichia coli using the general aromatic amino acid transport system and a specific phenylalanine transport system [13].

Biological context of 5-amino-5-carboxy-2-hydroxy-pent-1-ene-1-diazonium

• Inactivation of rat renal phosphate-dependent glutaminase with 6-diazo-5-oxo-L-norleucine. Evidence for interaction at the glutamine binding site [14].
• Phase I study and clinical pharmacology of 6-diazo-5-oxo-L-norleucine (DON) [4].
• Cell cycle phase perturbations by 6-diazo-5-oxo-L-norleucine and acivicin in normal and neoplastic human cell lines [15].

Anatomical context of 5-amino-5-carboxy-2-hydroxy-pent-1-ene-1-diazonium

• We have investigated the biosynthesis of heparan sulfate proteoglycan in human colon carcinoma cells cultured in either the absence of L-glutamine or the presence of 6-diazo-5-oxo-L-norleucine (DON), a glutamine analogue [16].
• Incorporation of [35S]sulphate by cultures of matrix-free cells from chick embryo sterna in the presence of the glutamine analogue 6-diazo-5-oxo-L-norleucine (0.58 mM) was inhibited in a time-dependent manner to less than 15% of that in control cultures after 2 h [17].
• Bovine venular endothelial cells were cultured for 24 h in the presence of 0, 0.1, 0.5 or 2 mM D-glucosamine, or of 0.2 or 2 mM L-glutamine with or without 20 microM 6-diazo-5-oxo-L-norleucine (DON) or with 100 microM azaserine [18].
• 6-diazo-5-oxo-L-norleucine (DON) exerts a growth inhibitory effect selectively on the neuroendocrine tumour cell line BON and is proposed as an antitumour drug [19].
• We have examined transport and membrane binding of 6-diazo-5-oxo-L-norleucine (DON, a photoactive diazo-analogue of glutamine) and their relationships to glutamine transport in Xenopus laevis oocytes [20].

Associations of 5-amino-5-carboxy-2-hydroxy-pent-1-ene-1-diazonium with other chemical compounds

• In addition, the presence of o-carbamoyl-L-serine was found to stimulate inactivation by 6-diazo-5-oxo-L-norleucine, but to protect the glutaminase against inactivation by the chloroketone [14].
• An inhibitor of glutamate synthase activity, 6-diazo-5-oxo-L-norleucine, inhibited nitrogenase activity in the absence of NH4+, but only in cells exposed to low light [21].
• The formation of [13N]glutamine and [13N]glutamate by NH4+-grown cells was inhibited in the additional presence of methionine sulfoximine (an inhibitor of GS) and diazooxonorleucine (an inhibitor of GOGAT) [22].
• Glutamate immunoreactivity in rat cerebral cortex is reversibly abolished by 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of phosphate-activated glutaminase [23].
• Determination of 6-diazo-5-oxo-L-norleucine in plasma and urine by reversed-phase high-performance liquid chromatography of the dansyl derivative [24].

Gene context of 5-amino-5-carboxy-2-hydroxy-pent-1-ene-1-diazonium

• On the other hand, inhibition by 6-diazo-5-oxo-l-norleucine of the rate-limiting enzyme in hexosamine biosynthesis blunted EPA-induced stimulation of leptin mRNA expression and its secretion [25].
• Inactivation of rat renal phosphate-dependent glutaminase by 6-diazo-5-oxo-L-norleucine occurs only under conditions where the enzyme is catalytically active [14].
• Radiolabeled protein is not observed (i) when the wild-type enzyme is incubated with 6-diazo-5-oxo-L-norleucine (DON) prior to reaction with [14C]glutamine or (ii) when the C1A AS-B mutant is incubated with [14C]-L-glutamine [26].
• The mechanism of 6-diazo-5-oxo-L-norleucine inhibition appeared to be the same as that induced by NH4+, because nitrogenase activity could be restored in vitro by activating enzyme and Mn2+ [21].
• GMP is a considerably more potent inhibitor of the human lymphoblast enzyme than is AMP; 6-diazo-5-oxo-L-norleucine inhibits only glutamine-dependent activity and has no effect on ammonia-dependent activity [27].

Analytical, diagnostic and therapeutic context of 5-amino-5-carboxy-2-hydroxy-pent-1-ene-1-diazonium

• Using an organ culture model in which fetal murine thymuses explanted on gestational day 14 undergo phenotypic maturation from CD3-CD4-CD8- to CD3+CD4+/CD8+, the consequences of inhibiting GAG synthesis with 6-diazo-5-oxo-L-norleucine (DON) were explored [28].

References