人白细胞介素11的定点聚乙二醇修饰

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。

Site-specific PEGylation of Engineered Cysteine Analogues of Recombinant Human Interleukin-11

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.