Hadley K B, Sato P H
Laboratory of Biochemistry, National Cancer Institute, Bethesda, Md.
Enzyme. 1989;42(4):225-34. doi: 10.1159/000469036.
Scurvy in guinea pigs provides a convenient model of inborn metabolic disease for the investigation of enzyme therapy protocols. Gulonolactone oxidase, the enzyme in ascorbic acid biosynthesis that is missing from the scurvy-prone species, was modified by attachment of polyethylene glycol. The catalytic properties of this enzyme were affected little by the modification. Intravenous injection of this modified form of the enzyme elicited ascorbic acid synthesis in a dose-dependent manner. The modified enzyme was stabilized to incubation at 37 degrees C but was not protected from inactivation by trypsin. The circulating half-life of enzyme activity was not prolonged by this modification. Further, attachment of polyethylene glycol did neither abolish the enzyme's ability to react with preformed antibodies nor eliminate its immunogenicity.
豚鼠坏血病为研究酶疗法方案提供了一种方便的先天性代谢疾病模型。古洛糖酸内酯氧化酶是抗坏血酸生物合成中易患坏血病物种所缺乏的酶，通过连接聚乙二醇进行了修饰。这种修饰对该酶的催化特性影响很小。静脉注射这种修饰形式的酶会以剂量依赖的方式引发抗坏血酸合成。修饰后的酶在37℃孵育时稳定，但不能防止被胰蛋白酶灭活。这种修饰并没有延长酶活性的循环半衰期。此外，聚乙二醇的连接既没有消除该酶与预先形成的抗体反应的能力，也没有消除其免疫原性。
