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聚乙二醇修饰的蓖麻毒蛋白A链的特性研究
引用本文:黎维勇,方凯,郭文韬,戴垚,谌辉,陈华庭. 聚乙二醇修饰的蓖麻毒蛋白A链的特性研究[J]. 中国医院药学杂志, 2006, 26(8): 915-918
作者姓名:黎维勇  方凯  郭文韬  戴垚  谌辉  陈华庭
作者单位: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
3. 中国医学科学院中国协和医科大学医药生物技术研究所,北京,100050
摘    要:目的:研究两种不同相对分子质量(Mr)的单甲氧聚乙二醇(Monomethoxy polyethylene glycol,mPEG)与蓖麻毒蛋白A链(ricin A-chain,RTA)偶联后三者的免疫原性和毒性的不同。方法:从天然蓖麻籽中提取纯化的RTA,并分别与相对分子质量为5KD和10KD的mPEG反应偶联,得到两种不同的RTA-mPEG偶联物。用蛋白质印迹方法比较RTA和不同的RTA-mPEG偶联物之间的免疫原性的变化,此外通过用噻唑蓝比色法(MTT)对RTA及不同偶联物的体外细胞毒性进行评价,并通过测定半数致死量(LD50)的方法比较它们的体内毒性。结果:经聚乙二醇修饰后的RTA,其毒性有明显的下降。此外,对其免疫原性的研究表明,RTA的PEG化也能降低RTA的免疫原性。结论:聚乙二醇能遮蔽RTA,使其免疫原性和毒性有很大的降低。且下降的程度同与RTA偶联的聚乙二醇的相对分子量成正相关。

关 键 词:蓖麻毒蛋白A链  聚乙二醇  免疫原性  毒性
文章编号:1001-5213(2006)08-0915-04
收稿时间:2005-12-21
修稿时间:2005-12-21

Study on the properties of Ricin A-chain modified by polyethylene glycol
LI Wei-yong,FANG Kai,GUO Wen-tao,DAI Yao,CHEN Hui,CHEN Hua-ting. Study on the properties of Ricin A-chain modified by polyethylene glycol[J]. Chinese Journal of Hospital Pharmacy, 2006, 26(8): 915-918
Authors:LI Wei-yong  FANG Kai  GUO Wen-tao  DAI Yao  CHEN Hui  CHEN Hua-ting
Affiliation:1. Union Hospital Affliated to Tongji Medical College, Huazhong University of Science and Technology, Hubei Wuhan 430022, China; 2. School of Life Science and Technology, Huazhon4g University of Science and Technology, Hubei Wuhan 430074, China; 3. Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences Peking Union Medical College, Beijing 100050, China
Abstract:OBJECTIVE To study the difference in immunogenicity and toxicity of ricin A-chain(RTA) and RTA-mPEGs.METHODS RTA and PEG-RTA conjugates modified by polyethylene glycol (PEG) with different MW ( 5 000 and 10 000 ) were prepared. The immunogenicity of RTA and RTA-mPEG was compared by Western blot method. The in vivo and in vitro toxicity was compared by the determination of LD_ 50 and MTT method respectively. RESULTS The immunogencity and toxicity of RTA modified by mPEG were reduced remarkably. CONCLUSION Immunogenicity and toxicity of RTA-mPEG decrease significantly compared with free RA probably as PEG can cover RTA. The decreasing txtent is proportional to molecular weight of the PEG.
Keywords:Ricin A-chain   polyethylene glycol   immunogenicity   toxicity
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