去唾液酸糖蛋白受体介导的肝靶向脂质体配体的酶促催化合成研究

Study on the Enzyme-Catalyzed Synthesis of Ligands for ASGPR-mediated Liver Targeting Liposomes

目的用酶促催化乳糖酸与十八胺合成一种可用于镶嵌脂质体表面的去唾液酸糖蛋白靶向配体修饰物。方法通过红外光谱(IR)、质谱(ESI-MS)和核磁共振(1H-NMR)对产物结构进行确证,并对酶种类、反应介质、酶的加入量、底物摩尔比、反应温度等影响因素进行考察。结果二甲基亚砜作为反应介质;Novozym 435固定化脂肪酶作为催化剂、酶加入量为400U.mL-1、乳糖酸和十八胺的摩尔比为2∶1、40℃下反应24 h,十八胺的转化率可达99%以上。结论酶促催化法可用来合成肝靶向脂质体配体。

OBJECTIVE To synthesize asialoglycoprotein receptor ligand-targeted modifier which is used to insert the surface of liposome by enzyme-catalyzed amidation of laetobionic acid and stearamine. METHODS The structure of the product was confirmed by IR, ESI-MS and ^1H-NMR. The effects of types and quantity of enzyme, organic solvents, molar ratio of substrate and temperature of reaction were studied. RESULTS When using DMSO as reaction medium, Novozym 435 immobilized lipase at 400 U·mL^-1 , molar ratio of lactobionie acid to stearamine at 2： 1, and reacting at 40 ℃ for 24 h, the transformation of stearamine reached more than 99%. CONCLUSION The enzyme catalysis is useful for synthesizing liver targeting liposomes.