多聚唾液酸对L-天冬酰胺酶的修饰及修饰酶特性研究

来源于大肠杆菌 (Ｅ .ｃｏｌｉ)的Ｌ 天冬酰胺酶是治疗淋巴性白血病和恶性淋巴肿瘤的有效酶制剂 ,已应用于临床。该酶与其他蛋白质类药物一样 ,在临床应用中存在两个常见问题 :一是酶制剂在体内易被降解 ,导致半衰期短 ;二是免疫原性。为了解决上述问题 ,人们用亲水性的大分子如血清蛋白、右旋糖苷和单甲氧基聚乙二醇 (ｍＰＥＧ)对该酶进行修饰。其中ｍＰＥＧ1] 修饰后的Ｌ 天冬酰胺酶的抗原抗体结合能力完全消失 ,免疫原性下降 ,且体内半衰期延长 ;但酶活力只有天然酶的 8%～ 14% ,且ｍＰＥＧ在人体组织中无法降解 ,目前尚难评估长期使用…

Modification of L-asparaginase with Colominic Acid and the New Characteristics of the Modified Enzyme

The colominlc acid was covalently coupled to L-asparaginase molecule by reductive amination. Depending on the molar ratios of colominic acid-asparaginase (301,501 and 1001),a modified enzyme molecule contained 4.7,7.2 and 12 colominic acid molecule,they retained 58%,56% and 33.2% of the initial asparaginase activity,respectively. In comparison with the native enzyme, modified enzyme had lower immunogenicity and antigenicity,longer half-life time (in uitro ),more resistance ability to trypsin proteolysis, and similar Km value for L-asparagine.