人白细胞介素11的定点聚乙二醇修饰

中国生物工程杂志

研究报告

人白细胞介素11的定点聚乙二醇修饰

李智华胡满仓阎玲梅赵玉娇杨旭彭正华徐维明李健峰

中国医学科学院中国协和医科大学医学生物学研究所

Site-specific PEGylation of engineered cysteine analogues of recombinant human interleukin-11

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摘要：

利用人白细胞介素11（hIL-11）无半胱氨酸（Cys）残基这一特点，通过定点突变将一个Cys残基引入hIL-11的N末端。然后，利用与Cys 巯基特异性反应的mPEG-马来酰亚胺将mPEG偶联到预先选定的位点，经层析纯化得到hIL-11的定点PEG修饰物。利用依赖型细胞株7TD1测定其生物学活性，结果表明，其体外生物学活性保持原有hIL-11活性的30%左右。定点聚乙二醇修饰方法为定向改造hIL-11，提高其药效的应用研究打下基础。

关键词： 人白细胞介素11;聚乙二醇;化学修饰

Abstract:

Human Interleukin-11(hIL-11) has no Cys residue in its natural form. By site-directed mutagenesis ,a Cys residue can be introduced to replace the 1st residue Gly and the rhIL11 was chemically modified by using 20 kDa mPEG-maleimide conjugated to this site. The mPEG-hIL-11 conjugate was purified and showed a single band on SDS-PAGE with an apparent molecular weight. The biological activity of purified mPEG-hIL-11 was determined using a dependent cell line 7TD1. The remaining biological activity of PEGylated-rhIL-11 was 30% of native rhIL-11, suggesting chemical modification of rhIL-11 by PEG is a promising approach for improving the pharmacological efficacy.

Key words: human interleukin-11(hIL11);Polyethylene glycol;Chemical modification

收稿日期: 2009-02-16 出版日期: 2009-07-02

基金资助:

云南省自然科学基金

通讯作者: 李健峰 E-mail: lijianfeng73@gmail.com

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引用本文:

李智华,胡满仓,阎玲梅,赵玉娇,杨旭,彭正华,徐维明,李健峰. 人白细胞介素11的定点聚乙二醇修饰[J]. 中国生物工程杂志, .

LI Zhi-Hua- Hu-Man-Cang- Yan-Ling-Mei- Diao-Yu-Jiao- Yang-Xu- Bang-Zheng-Hua- Xu-Wei-Meng- Li-Jian-Feng. Site-specific PEGylation of engineered cysteine analogues of recombinant human interleukin-11. China Biotechnology, .

链接本文:

https://manu60.magtech.com.cn/biotech/CN/ 或 https://manu60.magtech.com.cn/biotech/CN/Y2009/V29/I06/20

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