中文摘要：

对Candida utilis来源的尿酸酶进行定点修饰，并对修饰前后尿酸酶酶学性质的改变进行了研究。PEG修饰使尿酸酶的最适pH往中性偏移，最适温度反应曲线展宽，与底物亲和力增加但最大反应速率降低，在低离子强度条件下更加稳定，对尿酸酶结合金属离子及阴离子的能力有弱化作用。研究结果显示：PEG修饰不仅可以通过屏蔽效应改善尿酸酶的药代动力学性质，也可能通过影响尿酸酶亚基解离、亚基表面电荷分布等性质而影响尿酸酶的酶学性质。这些结果为新药开发PEG-尿酸酶提供了基础。

英文摘要：

In our study the Escherichia Coli to express the recombinant Candida utilis uricase,was ased and modified at N-terminal by site-specific PEGylation with PEG-ALD-20000, and the change of enzymology character of the conjugate after PEGylation was also studied systematically. The results showed that, compared to nature uricase, optimal pH value of conjugate had a migration to neutral pH value, the curve of optimal temperature was boarder, substrate affinity increased but the Vmax reduced, more stable in low ionic strength environment, and the capability of binding negative ion and metal ion were weak. From these results it could be concluded that PEGylation could improve the pharmacokinetics properties of uricase not only by shielding effect, also by the effect on the subunit dissociation and charge distribution on the subunit surface. These results provide a basis on the rational design and new drug development of PEG-uricase.