Preparation of a polyethylene glycol: superoxide dismutase adduct, and an examination of its blood circulation life and anti-inflammatory activity.
Preparation of a polyethylene glycol: superoxide dismutase adduct, and an examination of its blood circulation life and anti-inflammatory activity.
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聚乙二醇超氧化物歧化酶加合物的制备及其循环寿命和抗炎活性的测定。
DOI：
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发表时间：
1980
期刊：
影响因子：
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通讯作者：
F. Davis
中科院分区：
文献类型：
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作者：
P. S. Pyatak;A. Abuchowski;F. Davis
牛红细胞超氧化物歧化酶的20个赖氨酸残基中有19个与5000道尔顿的甲氧基聚乙二醇（PEG）共价连接。该加合物（PEG-超氧化物歧化酶）的酶活性为超氧化物歧化酶的51%。PEG-超氧化物歧化酶表现出显着增强的血清循环寿命在重复静脉注射相比，天然酶。虽然没有观察到对重复注射PEG-超氧化物歧化酶的免疫应答的证据，但未修饰的酶似乎以在30天内注射13次后从血清中更快去除的形式产生轻微致敏作用。然而，超氧化物歧化酶和PEG-超氧化物歧化酶的抗血清不产生可检测的抗体，如通过Ouchterlony方法所确定的。腹腔注射PEG-超氧化物歧化酶比超氧化物歧化酶更容易进入血流。PEG修饰略微提高了酶的抗炎活性，这在大鼠中观察了8天。
Methoxypolyethylene glycol (PEG) of 5000 daltons was attached covalently to 19 of the 20 available lysine residues of bovine erythrocyte superoxide dismutase. The adduct (PEG-superoxide dismutase) has 51% of the enzymatic activity of superoxide distmutase. PEG-superoxide dismutase exhibits a sharply enhanced serum circulating life during repetitive intravenous injections compared to the native enzyme. While no evidence of an immune response to repetitive injections of PEG-superoxide dismutase is observed, the unmodified enzyme appears to produce slight sensitization in the form of quicker removal from the serum after 13 injections over a period of 30 days. Antisera to superoxide dismutase and PEG-superoxide dismutase, however, produce no detectable antibodies as determined by the Ouchterlony method. Intraperitoneally injected PEG-superoxide dismutase enters the bloodstream more readily than superoxide dismutase. PEG modification slightly improves the enzyme's anti-inflammatory activity, which was observed in rats over a period of eight days.