Modification of Escherichia coli B glutathione synthetase with polyethylene glycol for clinical application to enzyme replacement therapy for glutathione deficiency.

Glutathione synthetase of Escherichia coli B was modified with polyethylene glycol, and the properties of the resultant modified enzyme were investigated. The thermal stability of the modified enzyme and its resistance against several proteases increased compared with those of the native enzyme. The modified enzyme was injected intravenously via the rat tail vein, and the circulating life of the enzyme in plasma was monitored. The half-life of the native enzyme was 50 min, whereas that of the modified enzyme was approximately 24 h. The systemic anaphylaxis reaction was tested by using rats intravenously injected with the native and modified enzymes. For the native enzyme, strong reactions such as dyspnea and tumble were observed; however, no symptom or only a very weak reaction, such as scratching, was observed with the modified enzyme.