Chemical modification of superoxide dismutase. Extension of plasma half life of the enzyme through its reversible binding to the circulating albumin.
Chemical modification of superoxide dismutase. Extension of plasma half life of the enzyme through its reversible binding to the circulating albumin.
复制标题
超氧化物歧化酶的化学修饰。
DOI：
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Y. Morino
中科院分区：
文献类型：
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作者：
T. Ogino;M. Inoue;Y. Ando;M. Awai;H. Maeda;Y. Morino
保护生物体免受氧化应激是有氧生命的主要先决条件之一。由于静脉注射的铜+/锌+型超氧化物歧化酶(SOD)迅速通过肾小球滤过，并以其完整的形式出现在尿液中，其作为超氧阴离子自由基清除剂的临床应用受到高度限制。为了测试人红细胞型酶的赖氨基残基与聚苯乙烯-马来酸丁酯(SMA)的可逆性相互作用是否可以降低酶在循环中的消失率，用酰胺键将人红细胞型酶的赖氨基残基与SMA共价连接。白蛋白-琼脂糖柱亲和层析分析表明，SMA标记的酶样品(SMA-SOD)紧密结合在柱上，而未修饰的SOD在未结合组分中洗脱。用含0.1%十二烷基硫酸钠的缓冲溶液可洗脱结合在柱上的SMA-SOD。体内分析表明，静脉注射SMA-SOD与白蛋白结合的半衰期极长(6h)，而未修饰的SOD迅速通过肾小球滤过，血浆半衰期为4min。因此，SMA-SOD可有效清除循环中的超氧阴离子自由基。
Protection of organisms from oxidative stress is one of the major prerequisites for aerobic life. Since intravenously injected Cu++/Zn++-type superoxide dismutase (SOD) rapidly undergoes renal glomerular filtration and appears in urine in its intact form, its clinical use as a scavenger for superoxide radicals has been highly limited. To test whether reversible interaction of SOD with plasma albumin might decrease the rate of disappearance of the enzyme from the circulation, the lysyl residues of the human erythrocyte-type enzyme were covalently linked with poly-(styrene-co-maleic acid) butyl ester (SMA) via amide linkage. Affinity chromatographic analysis by an albumin-Sepharose column revealed that the enzyme samples labeled with SMA (SMA-SOD) tightly bound to the column, while unmodified SOD was eluted in the unbound fractions. SMA-SOD bound to the column could be eluted by the buffer solution containing 0.1% sodium dodecylsulfate. In vivo analysis revealed that intravenously administered SMA-SOD circulated bound to albumin with an extremely long half-life (6 h), while unmodified SOD rapidly underwent renal glomerular filtration with a plasma half-life of 4 min. Thus, SMA-SOD may effectively dismutase superoxide radicals in the circulation.
影响因子：
5.6
作者：
TAINER, JA;GETZOFF, ED;RICHARDSON, DC
通讯作者：
RICHARDSON, DC
影响因子：
11.2
作者：
Y. Matsumura;H. Maeda
通讯作者：
Y. Matsumura;H. Maeda