重组人促红素等电点异构体分子体内活性强度分析  

In vivo biological activity strength of isoelectric point isoform molecules of recombinant human erythropoietin

作　　者：史新昌[1] 李响[1] 于雷[1] 周勇[1] 饶春明[1] SHI Xin-chang;LI Xiang;YU Lei;ZHOU Yong;RAO Chun-ming(Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products,National Institute for Food and Drug Control,Beijing 100050,China)

机构地区：[1]中国食品药品检定研究院卫生部生物技术产品检定方法及其标准化重点实验室,北京100050

出　　处：《中国生物制品学杂志》2020年第5期549-553,共5页Chinese Journal of Biologicals

基　　金：重大新药创制“重组DNA药质控和报告基因研究(2018ZX09101001-004-002)”资助;《中国药典》药品标准提高“重组人细胞因子类产品质控替代方法(2018S001)”资助。

摘　　要：目的分析重组人促红素(recombinant human erythropoietin,rhEPO)各等电点异构体分子体内活性强度(单位时间单位摩尔量下产生体内活性量),找出最适作用分子。方法根据rhEPO等电点异构体体内比活性数据变化,构建等电点异构体分子与其体内活性之间关系的数学模型,并进行解析。结果得到rhEPO等电点异构体分子体内活性与唾液酸数量关系:Si=0.628·e^(i-10)·(|i-10|+1)^-2+0.492,R^2>0.9880(i为正整数且16>i>8,表示rhEPO分子上唾液酸数量;Si表示某等电点异构体体内比活性,体内比活性单位10^5 IU/mg),在此基础上,进而提出rhEPO与其受体相互作用模型假说(电荷识别-分子内氢键重排-构象变化-排斥解离假说)。结论通过对rhEPO等电点异质性与体内比活性关系的进一步分析,阐述了rhEPO与其受体相互作用存在最适作用分子,并依据上述实验和数据分析提出了rhEPO与其受体相互作用的模型假说,为rhEPO体内和体外活性的研究提供了思路。Objective To analyze the in vivo biological activity strengths of isoelectric point isoform(IF)molecules of recombinant human erythropoietin(rhEPO)(in vivo biological activity under unit molar quantity in unit time)and find out the optimal IF molecules to act on their receptors.Methods According to the change of data on in vivo specific activity of isoelectric point IF of rhEPO,the mathematical model of relationship between IF molecules and their activities in vivo was constructed and analyzed.Results The relationship between the in vivo specific activity of sialic acid was as follows:Si=0.628·e^(i-10)·(|i-10|+1)^-2+0.492,R^2>0.9880,where i is a positive integer more than 8 but less than 16,indicating the amount of sialic acid on rhEPO molecules.Sirepresents the in vivo specific activity of isoelectric point IF of rhEPO,of which the unit is 10^5 IU/mg.On the basis of this,the hypothesis of interaction model between rhEPO and its receptor was put forward and named as charge recognition-intramolecular hydrogen bond rearrangementconformation change-reject dissociation(CICR)hypothesis.Conclusion This paper suggests that there are optimal molecules for interaction between rhEPO and its receptor through the analysis of relationship between isoelectric point isoforms and its in vivo specific activity,based on which a hypothesis of interaction model between rhEPO and its receptor was put forward.It provides a novel way for study on the in vivo and in vitro activities of rhEPO.

关 键 词：重组人促红素 等电点异构体 体内比活性 最适作用分子 电荷识别-分子内氢键重排-构象变化-排斥解离假说 

分 类 号：R917[医药卫生—药物分析学]