肝脏去唾液酸糖蛋白受体的配体制备研究.doc

肝脏去唾液酸糖蛋白受体的配体制备研究 石红 余进洪 刘健 川北医学院附属医院超声科 南充 637000 [摘要]目的：优化制备出具有高效性的肝脏去唾液酸糖蛋白受体（ASGPR）的配体半乳糖化多聚赖氨酸（Galactocylated Poly-L-Lysine，Gal-PLL），为后期的肝靶向性纳米液态氟碳微球超声造影剂的制备以及肝脏靶向分子成像提供前提及奠定基础。方法：采用还原胺化法[1]，根据各反应组分的比例不同总体分为2组：A组、B组，每组中又分别细分成3组，A组中将三种不同摩尔比的半乳糖和多聚赖氨酸分别与等量足量还原剂硼氢化钠进行反应，B组将相同摩尔比的半乳糖和多聚赖氨酸分别与三种不同量还原剂进行反应。每组的产物均经葡聚糖凝胶柱分离纯化，得到不同化合物分子量的达峰曲线并对此进行分析。结果：当还原剂等量时，适量减少D-半乳糖的量，分离纯化的化合物分子量达峰曲线提前；当D-半乳糖与多聚赖氨酸摩尔比相等时，适当减少还原剂的量，分离纯化的化合物分子量达峰曲线亦出现提前，当D-半乳糖与还原剂的摩尔比为1：1时，反应合成的半乳糖化多聚赖氨酸化合物与游离组分的曲线分离最为明显，且化合物的量达到最大。结论：当还原剂等量时，适量减少D-半乳糖可以增加D-半乳糖与多聚赖氨酸的偶联效果，而当D-半乳糖与多聚赖氨酸摩尔比相等时，适量减少还原剂，D-半乳糖与多聚赖氨酸的偶联效果更佳，当D-半乳糖与还原剂的摩尔比为1：1时，D-半乳糖与多聚赖氨酸的偶联效果最好。D-半乳糖与多聚赖氨酸的偶联不仅与两者的配比相关，也与D-半乳糖与还原剂的配比相关。 [关键词]D-半乳糖；多聚赖氨酸；还原胺化反应 Study on the Preparation of Ligand of Hepatic Asialoglycoprotein Receptor Shi Hong, Yu Jinhong, Liu Jian. Department of Medical Ultrasound, the Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China [Abstract] Objective：To optimize the preparation of high-efficiency Galactocylated Poly-L-Lysine（Gal-PLL）ligand of the asialoglycoprotein receptor in liver, providing premise and foundation for upper preparation of ultrasound contrast agent of liver targeted nanoscale perfluorocarbon microballoon and the liver targeted molecular imaging. Methods：Chemical reactions of reductive amination were divided into A group and B group according to different proportions of reaction component. Every group was subdivided into three subgroups. In A group , three different molar ratios of D-galactose and Poly-L-Lysine(PLL) were compounded respectively with equivalent and sufficient reductant borohydride.In B group, identical molar ratios of D-galactose and PLL were compounded respectively with three unequal reductants borohydride. Products of each group were separated and purified by sephadex column to acquire different molecular weight distributions and the results were analyzed. Results: In the condition of identical reductant,the peak curve of compound’s molecular weight