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DC FieldValueLanguage
dc.contributorDepartment of Applied Biology and Chemical Technologyen_US
dc.creatorTsui, Sam-mui-
dc.identifier.urihttps://theses.lib.polyu.edu.hk/handle/200/3240-
dc.languageEnglishen_US
dc.publisherHong Kong Polytechnic University-
dc.rightsAll rights reserveden_US
dc.titleThe development of human recombinant arginase as a novel agent in the treatment of human canceren_US
dcterms.abstractSome tumour cells have been shown to be auxotrophic for arginine. Enzyme degradation of extracellular arginine becomes a possible mean for inhibiting tumour growth but harmless to normal cells. Arginase is one of the arginine depriving enzymes that catalyses the hydrolysis of arginine to urea and ornithine. Arginase was shown by others to have anti-tumour activity and is potentially useful for treatment of cancer. In 1990, recombinant human arginase was produced successfully from an Escherichia coli expression system. However, E. coli is pathogenic and the yield of arginase was low. To overcome these problems, we produced recombinant human arginase using a non-pathogenic prophage-based Bacillus subtilis expression system. In addition, the arginase was tagged with 6 histidines at the N-terminus to allow single-step purification, by which about 100 mg of arginase was obtained from 1 L of fermentation culture in unprecedented high purity as well as activity. In phosphate-buffered saline buffer (pH 7.4), the purified enzyme is a dimer with Km and kcat values of 1.89 mM and 1.80 s-1, respectively, and the specific activity is 500-600 I.U. mg-1. The blood circulation half-life of the recombinant arginase was found to be too short and was not effective to deplete serum arginine. To overcome this problem, the enzyme was modified with polyethylene glycol (PEG) to produce pegylated arginase, arginase-SPA-PEG5000- Arginase-SPA-PEG5000 is fully active, with substantially increased circulation half-life, and retains all the enzyme kinetic parameters as the native arginase. When given a single intraperitoneal (i.p.) injection of 1,500 I.U. of arginase-SPA-PEG5000 to rats, the plasma arginine level was decreased to a non-detectable level for about six days. These data indicate that the pegylated human arginase, arginase-SPA-PEG5000, is safe and could be further developed to function as an effective arginine depriving anti-cancer drug.en_US
dcterms.extentvi, 166 leaves : ill. ; 30 cm.en_US
dcterms.issued2004en_US
dcterms.educationalLevelAll Masteren_US
dcterms.educationalLevelM.Phil.en_US
dcterms.LCSHHong Kong Polytechnic University -- Dissertations.en_US
dcterms.LCSHArginine.en_US
dcterms.LCSHCancer -- Treatment.en_US
dcterms.accessRightsopen accessen_US

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