title: Reduction in immunogenicity and clearance rate of Escherichia coli L-asparaginase by modification with monomethoxypolyethylene glycol.
abstract: Escherichia coli L-asparaginase was modified with monomethoxypolyethylene glycol using cyanuric chloride as a coupler. The modified enzyme did not cross-react with anti-L-asparaginase antibody in precipitin reaction, but retained some catalytic activity (8% of the original activity). It has the same Km value for L-asparagine and the same optimal pH as the native enzyme. The immunogenicity of the modified enzyme was substantially reduced because mouse antiserum to it showed no significant increase in hemagglutinin titer of L-asparaginase-coated sheep red blood cells. After a single i.p. injection of the modified enzyme (80 I.U./kg) into rats, enzyme activity was detected in the serum within 30 min and persisted for over 3 weeks. Concomitant depletion of serum L-asparagine persisted for more than 3 weeks. On the other hand, the active enzyme was rapidly cleared from the serum. The half-lives of the modified and native enzymes were calculated to be 56 and 2.9 hr, respectively. This modified L-asparaginase may be much more useful than the native enzyme for the clinical treatments of tumors because of its reduced immunogenicity.
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001215:Asparaginase / Q000276:immunology* / Q000378:metabolism; D001216:Asparagine / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D005026:Ethylene Glycols; D005260:Female; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D005026:Ethylene Glycols; D001216:Asparagine; D001215:Asparaginase