糖苷类化合物血浆蛋白结合的研究  

The study on plasma protein binging of glucoside compounds

作　　者：刘斐[1,2] 张士俊[1] 徐为人[1] 申秀萍[1] 商倩[1] 汤立达[1] 

机构地区：[1]天津药物研究院释药技术与药代动力学国家重点实验室,天津市新药设计与发现重点实验室,天津300193 [2]天津中医药大学,天津300193

出　　处：《天津中医药》2013年第10期621-625,共5页Tianjin Journal of Traditional Chinese Medicine

基　　金：国家重大新药创制专项(2011ZX09401-009;2010ZX09401-307-1-1);天津科技支撑项目"新型SGLT2抑制剂"

摘　　要：[目的]考察dapagliflozin及其衍生物与大鼠血浆蛋白的结合规律以及结合位点。[方法]采用平衡透析法和高效液相色谱法(HPLC)测定血浆蛋白结合率,选出代表性化合物与地西泮和华法林进行竞争性结合实验,利用对接计算进行结合位点的初步研究。[结果]dapagliflozin的蛋白结合率随着血浆比例的增加而增大,糖苷类化合物结构变化对蛋白结合率也有一定影响,地西泮和华法林对糖苷类化合物的蛋白结合影响较小,对接结果表明糖苷类化合物主要与白蛋白的第2个亚结构结合。[结论]dapagliflozin及其衍生物具有较高的血浆蛋白结合能力,可能结合在与华法林和地西泮不同的白蛋白结合位点,结构的变化可以一定程度改变蛋白结合率。[Objective] To investigate the relationship between structure and protein binding rate, and explore the possible binding position of dapagliflozin and its derivatives. [Methods] The plasma balance dialysis and HPLC analysis were used to determine the protein binding rate of glucoside compounds. A few representative derivatives were for competitive combination experiment with diazepam and warfarin. The docking calculation was used to explore the binding position to human albumin of glucoside compounds. [Results] The pro- tein binding rate of dapagliflozin was related to plasma volume used. The modification of dapagliflozin structure could change the protein binding rate of glucoside compounds to some degree. The existence of warfarin and diazepam could not change protein binding rate of glucoside compounds too much. [Conclusion] Dapagliflozin and its derivatives showed strong binding ability with serum protein. Their binding site with albumin may be different with that of diazepam and warfarin. The modification of structure could change the binding ability to a certain degree.

关 键 词：糖苷类化合物 蛋白结合率 结合位点 

分 类 号：R285.5[医药卫生—中药学]