Research on PEG modification of uricase
- VernacularTitle:聚乙二醇修饰尿酸酶的研究
- Author:
Lei CAI
;
Xiangdong GAO
;
Shu ZHU
;
Hua WANG
;
Wenbing YAO
- Publication Type:Journal Article
- Keywords:
uricase;
PEGylation;
immunogenicity;
half-life
- From:
Journal of China Pharmaceutical University
2008;(6):557-562
- CountryChina
- Language:Chinese
-
Abstract:
To modify uricase with PEG reagent in order to decrease uricase immunogenieity and increase its stability.Methods:The branched PEG of 40 kD was chosen to modify native uricase.The properties of the mod-ified uricase including the stabilities to protease,pH and temperature,in vivo half-life time,as well as the immu-nogenicity were evaluated.The pharmacokinetic profiles of the midofied uricase were studied in mice.Results:It is demonstrated that the conjugation of PEG to lysine residues of Candida utilis uricase resulted in higher tryp-sin resistance.reduced immune response.and prolonged in vivo half-life.PEG modified uricase retained 80% of the enzymatic activity of native uricase.In addition,it was found that half-life in serum of the intravenously injec-ted PEGylated uriease of up to 696 min was longer that that of native uficase of 45 min.Higher plasma drug con-centrations were also reached with dosing of the PEGylated uricase to mice.Furthermore,the binding affinity Was shown to be reduced for the PEG-uricase using ELISA assay.and it was one-eishth that of native uricase.Final-ly,it Was indicated that the PEG uficase induced a delayed immunoresponse in mice following repeated adminis-trations.Conclusion:These findings demonstrate that this chemically modified form of uricase may serve as a potentially effective drug to treat gout patients.
