病毒性肝炎受体导向治疗药物的研究——Ⅰ.乳糖化白蛋白及其阿糖腺苷单磷酸酯偶合物的合成  

RESEARCH ON RECEPTOR TARGETING DRUGS FOR CHEMOTHERAPY OF VIRAL HEPATITIS Ⅰ. SYNTHESIS OF LACTOSAMINATED SERUM ALBUMIN AND ITS CONJUGATE WITH ADENINE ARABINOSIDE MONOPHOSPHATE

作　　者：仲伯华[1] 王亚平[1] 温守明[1] 龚雄麒[1] 王慧芬[2] 张玲霞[2] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]解放军302医院,北京100039

出　　处：《中国药物化学杂志》1993年第2期101-104,共4页Chinese Journal of Medicinal Chemistry

摘　　要：为了提高ara-AMP抗肝炎病毒作用的选择性,进行肝受体导向药物的研究。首先利用乳糖在氰基硼氢化钠作用下,与人血清白蛋白进行还原胺化反应,制备导向载体乳糖化白蛋白(Ⅱ);在碳二亚胺作用下,(Ⅱ)与ara-AMP缩合,制备药物载体偶合物(Ⅲ).每分子蛋白上连接28分子的半乳糖残基,15分子的药物。文中讨论了pH值对乳糖化反应及偶联反应的影响。初步评价结果表明,(Ⅱ)和(Ⅲ)在小鼠体内的分布具有较好的肝导向性,肝脏中偶合物的浓度可达心、血、脾等的4～8倍。In order to increase the chemotherapy index of adenine arabinoside monophosphate (ara-AMP), research on liver receptor-targeting drugs was carried out. The targeting carrier,lactosaminated human serum albumin(Ⅱ) was prepared by reductive amination of the protein with lactose in the presence of sodium cyanoborohydride. (Ⅱ) was then conjugated with araAMP. The molar incorportion ratio was obtained as HSA: Lactose: ara-AMP=1: 28: 15.The effect of pH on the reaction of lactosmination and the conjugating of (Ⅱ) with ara-AMP was discussed. Preliminary evaluation revealed that both (Ⅱ) and (Ⅲ) could be selectively delivered to the liver with concentrations 4～8 times as those in the heart,blood,spleen,etc.

关 键 词：导向治疗 ARA-AMP 乳糖化白蛋白 偶联 

分 类 号：R914[医药卫生—药物化学]