Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reductive coupling with sodium cyanoborhydride has been used with lactose and N-acetylneuraminyl lactose to prepare glycosylated Escherichia coli L-asparaginase. A substantial degree of modification can be achieved without significant loss of enzyme activity. The lactosylated enzyme shows increased thermal stability and resistance to proteolytic cleavage and is cleared more rapidly from the plasma of mice, compared to native asparaginase. The effect on clearance varies directly with the degree of lactosylation. Asparaginase modified with N-acetylneuraminyl lactose, in contrast, with approximately 13.6 mol of N-acetylneuraminyl lactose/mol of enzyme, is cleared more slowly, with a t 1/2 that is approximately twice that of the native enzyme.
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PMID:Glycosylation of Escherichia coli L-asparaginase. 33 66

The regulation mechanism of production of staphylococcal L-asparaginase was investigated. The role of cAMP in regulation of its synthesis was confirmed. Production of L-asparaginase from S. aureus NCTC 4135 was inhibited by all carbon sources, mono- and disaccharides added to the growth medium. The strongest inhibition was caused by saccharose and maltose, whereas weaker by galactose, lactose, mannitol and mannose. It was found that exogenous cAMP in the presence of carbon sources stimulated synthesis of the investigated enzyme.
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PMID:Staphylococcal L-asparaginase: catabolic repression of synthesis. 128 44

Maximum L-asparaginase activity was obtained when 1.0% lactose and 1.5% yeast extract were supplied as carbon and nitrogen sources, respectively. Glucose inhibited the enzyme formation. The diauxie phenomenon was observed with Erwinia aroideae NRRL B-138 grown in a medium containing glucose and lactose.
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PMID:L-Asparaginase synthesis by Erwinia aroideae. 502 78

Escherichia coli asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1) has been modified by succinylation, acetylation and the attachment of N,N-dimethyl-1,3-propanediamine and glucuronic acid. The effect of these modifications on plasma clearance rates in mice and on other properties is compared to the effects of modification with lactose and N-acetylneuraminyl lactose studied previously. The t 1/2 values for the acylated enzyme samples (lower pI) were reduced, succinylated asparaginase sharply and the acetylated enzyme less so. The N,N-dimethyl-1,3-propanediamine-modified samples (increased pI) also had lower t 1/2 values, but samples modified with glucuronic acid (reduced pI) showed little change in clearance time. The main conclusion is that the increased t 1/2 value found in the previous work for N-acetylneuraminyl-lactosylated enzyme is not due to the decreased pI value of the modified enzyme, but must be attributed to interference by N-acetylneuraminyl-lactose residues, directly or indirectly, with the mechanism normally used by the mouse to clear itself of injected E. coli asparaginase.
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PMID:Chemical modifications of Escherichia coli L-asparaginase and their effect on plasma clearance rate and other properties. 704 49

L-asparaginase, a therapeutic agent for the treatment of acute lymphoblastic leukemia, was evaluated for its susceptibility to cold denaturation. It was found that the enzyme derived from Erwinia chrysanthemi loses its activity when exposed to freeze-thaw cycling. When it was frozen at -40 degrees C and thawed, the enzyme lost 67.3% of its activity; whereas, when frozen in liquid nitrogen (-190 degrees C), it lost almost all of its activity. Rheological studies of hetastarch showed that its viscosity dramatically increases with decreasing temperature, suggesting that at sub-zero temperatures it will create a highly viscous environment around the enzyme. It is proposed that this highly viscous environment retards the rate of conformational changes leading to losses in activity. Hetastarch solutions of various concentrations and degrees of hydroxyethylation were evaluated for their protective ability against the freeze-thaw denaturation of L-asparaginase. It was found that the cryoprotective effect of hetastarch with 0.8 degree of substitution at a concentration of 0.2% was sustained over many freeze-thaw cycles while that of the lesser substituted starch was not. The cryoprotective effect of hetastarch was compared to that of other commonly used additives such as glucose and lactose, which failed to protect the enzyme from freeze-thaw denaturation. In addition, the protective effect of a monomer of hetastarch was evaluated in order to distinguish whether the protective effect of hetastarch was due to physicochemical interactions with the individual monomer units or to its polymeric nature. The monomer showed significant cryoprotection through the first freeze-thaw cycle which was not sustained over additional freeze-thaw cycles.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of hetastarch on the stability of L-asparaginase during freeze-thaw cycling. 754 44

When the enzyme Erwinia caratovora L-asparaginase was freeze-dried in mixtures of lactose and sodium chloride, biological activity and protein structure were preserved during drying. However, by altering the ratios of the excipients in the formulation it was possible to obtain products which were pharmaceutically acceptable or unacceptable as assessed by the criteria of dried cake appearance, moisture content or ease of reconstitution.
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PMID:Some implications of structural collapse during freeze-drying using Erwinia caratovora L-asparaginase as a model. 776 38

The production of L-asparaginase, an enzyme widely used in cancer chemotherapy, is mainly regulated by carbon catabolite repression and oxygen. This study was carried out to understand how different carbon sources and Vitreoscilla hemoglobin (VHb) affect the production of this enzyme in Pseudomonas aeruginosa and its VHb-expressing recombinant strain (PaJC). Both strains grown with various carbon sources showed a distinct profile of the enzyme activity. Compared to no carbohydrate supplemented medium, glucose caused a slight repression of L-asparaginase in P. aeruginosa, while it stimulated it in the PaJC strain. Glucose, regarded as one of the inhibitory sugars for the production L-asparaginase by other bacteria, was determined to be the favorite carbon source compared to lactose, glycerol and mannitol. Furthermore, contrary to common knowledge of oxygen repression of L-asparaginase in other bacteria, oxygen uptake provided by VHb was determined to even stimulate the L-asparaginase synthesis by P. aeruginosa. This study, for the first time, shows that in P. aeruginosa utilizing a recombinant oxygen uptake system, VHb, L-asparaginase synthesis is stimulated by glucose and other carbohydrate sources compared to the host strain. It is concluded that carbon catabolite and oxygen repression of L-asparaginase in fermentative bacteria is not the case for a respiratory non-fermentative bacterium like P. aeruginosa.
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PMID:Effect of Vitreoscilla hemoglobin on production of a chemotherapeutic enzyme, L-asparaginase, by Pseudomonas aeruginosa. 1689 49

GnRH is a promising target in hormone-dependent cancer immunotherapy. In our previous study, we have designed and purified a peptide vaccine GhM (GnRH3-hinge-MVP) by use of the bioprocess system based on asparaginase. Active immunization with GhM in the presence of CFA/IFA evoked strong humoral response. In this study, the motif NRLLLTG with high affinity to nanoparticle carrier VLP HBcDelta-SBD was fused to the C terminus of GhM to form a new peptide vaccine GhMNR (GnRH3-hinge-MVP-NRLLLTG). The fusion protein ansB-C-GhMNR was controlled by vigorous T7lac promotor and expressed effectively as inclusion bodies after induction by lactose and then purified by means of cell disruption, washing and cold ethanol fractionation. After hydrolyzed for 72 h, GhMNR was liberated from the fusion partner ansB-C and purified by CM52 cation exchange chromatography. These results suggested that the bioprocess system is suitable for large-scale expression and purification of the peptide vaccine GhMNR, and even some other proteins or peptides which may be important for industrial or laboratory purposes.
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PMID:Preparation of a peptide vaccine against GnRH by a bioprocess system based on asparaginase. 2063 28

L-asparaginase is a widely used cancer chemotherapy enzyme. The source for the enzyme with this property is mainly bacterial and its synthesis is strongly regulated by oxygen. In this study, we utilized two recombinant systems: one carried the gene (vgb) for the Vitreoscilla hemoglobin (VHb), a protein of prokaryotic origin which confers a highly efficient oxygen uptake to its host and the other carried the L-asparaginase gene (ansB). The host bacteria were Escherichia coli, Enterobacter aerogenes, and Pseudomonas aeruginosa. Of these three bacteria, all gram-negative, E. coli and its recombinant strain showed up to sevenfold higher L-asparaginase activity in lactose than in other carbon sources. Although, in this bacterium glycerol was the poorest source for L-asparaginase synthesis, it supported the highest biomass production. In glucose medium, L-asparaginase activity of E. aerogenes was about threefold higher than its vgb and ansB recombinants. ansB recombinant showed significantly higher enzyme levels than both host and vgb recombinants in glycerol and lactose media. In this bacterium, VHb/vgb clearly caused a decrease in the enzyme synthesis under all conditions. As seen for E. aerogens, glycerol was the most favorable carbon source for P. aeruginosa and its vgb strain in terms of both L-asparaginase synthesis and biomass production. The cultures grown in glycerol had more than two- and threefold biomass than in glucose and lactose, respectively, and up to elevenfold than in mannitol. Indeed, the highest biomass production for all bacteria and their recombinants was in glycerol. The VHb/vgb system is clearly advantageous for production of L-asparaginase in P. aeruginosa. The same, however, does not hold true for E. aerogenes.
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PMID:Effect of vitreoscilla hemoglobin and culture conditions on production of bacterial L-asparaginase, an oncolytic enzyme. 2497 46