半乳糖化重组人生长激素的制备及其肝靶向性

Preparation of galactosyl recombinant human growth hormone and its hepatic targeting

目的 :将重组人生长激素 (rhGH)进行半乳糖化修饰 ,制得半乳糖化重组人生长激素 (Gal rhGH) ,并研究其在小鼠体内的分布特征。方法 :以D 半乳糖为原料 ,制得双功能试剂 2 亚氨基 2 甲氧基乙基 1 硫代 β D 半乳吡喃糖苷 (IME) ,利用IME与重组人生长激素的碱性氨基酸偶合 ,制得Gal rhGH。以12 5I标记Gal rhGH和rhGH ,iv ,比较其在小鼠体内的组织分布。结果 :差热分析 (DTA)证实Gal rhGH是共价偶联物 ,平均糖密度为 5。iv后 ,12 5I rhGH Gal浓集于肝脏 ,最大分布量是12 5I rhGH的 2 .3倍 ;在肾脏 ,最大分布量仅为12 5I rhGH的 4 3 %。Gal rhGH在血、肝、肾、心、肺、脾、肠中全组织相对放射性分布的AUC分别是rhGH的 60 %,1 .5 5倍 ,5 8%,3 1 %,95 %,4 3 %,67%。结论 :成功地制备了化学偶联物Gal rhGH ,小鼠体内分布表明其具有明显的肝靶向性。

OBJECTIVE:To prepare galactosyl recombinant human growth hormone (Gal rhGH) and to study its distribution in mice.METHODS:A double function agent,2 imino 2 methoxyethyl 1 thio β D glycosides(IME) was prepared by D galactose through acetylation,bromination,condensation,displacement and addition reactions.Gal rhGH was prepared via IME attaching to the lysine residues on rhGH.RESULTS:Differential thermal analysis (DTA) verified that Gal rhGH was a covalent compound with mean 5 galactosyl residues per rhGH molecule.The comparative study of distribution in mice after iv showed that the radioactivity of 125 I rhGH Gal was concentrated in liver,whose maximum quantity was 2.3 times as that of 125 I rhGH.The distribution of 125 I rhGH Gal in kidney was 43% as that of 125 I rhGH.The AUC of whole tissue relative radioactivity distribution of 125 I rhGH Gal in blood,liver,kidney,heart,lung,spleen and intestine,were 60%,155%,58%,31%,95%,43%,67% as that of 125 I rhGH,respectively.CO NCLUSION:A hepatic targeting agent Gal rhGH was prepared successfully.