聚乙二醇修饰的蓖麻毒蛋白A链免疫原性与毒性的研究  

Inununogenicity and toxicity of ricin A-chain modified by polyethylene glycol

作　　者：黎维勇[1] 方凯[1] 宋波[1] 郭文韬[2] 陈华庭[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院,湖北武汉430022 [2]华中科技大学生命科学与技术学院,湖北武汉430074

出　　处：《中国药学杂志》2005年第13期1026-1028,共3页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金(30271552)

摘　　要：目的研究单甲氧聚乙二醇(mPEG)与蓖麻毒蛋白A链(RA)偶联后RA的免疫原性和毒性的改变。方法从天然蓖麻籽中提取纯化的RA,经与具有活性马来酰亚胺基团的mPEG反应偶联,得到纯化的mPEG偶联的RA。用蛋白质印迹方法比较RA修饰前后的免疫原性,通过测定半数致死量(LD50)的方法比较RA修饰前后的毒性。结果mPEG偶联的RA的免疫原性和毒性均明显下降。偶联前蓖麻蛋白A链的LD50为2.45mg·kg-1,而mPEG修饰的RA的LD50为3.67mg·kg-1。结论聚乙二醇能遮蔽RA,使其免疫原性和毒性有很大的降低。OBJECTIVE: To study the difference in immunogenicity and toxicity after coupling of ricin A-chain(RA) and RA-mPEG. METHODS: Monomethoxy polyethylene glycol (mPEG) was conjugated with RA through disulfide bond. The immunogenicity of RA and RA-mPEG was compared by Western blot method. And the toxicity of them was compared by the determination of their LD50. RESULTS: The immunogencity and toxicity of RA modified by mPEG were reduced remarkably. The LD50 of RA was 2.45 mg &middot kg-1, while the LD 50 of RA modified by mPEG was 3.67 mg &middot kg-1. CONCLUSION: The immunogenicity and toxicity of RA-mPEG decreased significantly compared with free RA. The possible reason was PEG could cover RA.

关 键 词：聚乙二醇 蓖麻毒蛋白A链 免疫原性 毒性 

分 类 号：R963[医药卫生—微生物与生化药学] Q51[医药卫生—药理学]