【摘要】 利用hIL-11无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。更多还原

【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 rhIL-11 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.更多还原