摘要
蛋白酪氨酸磷酸酶1B(protein tyrosine phosphatase 1B,PTP1B)是当前开发治疗糖尿病药物的优秀靶标,也是钒配合物抗糖尿病作用相关的重要靶蛋白.研究了三种含氮平面杂环螯合配体2,2'-联咪唑(L1),2,2'-联吡啶(L2),1,10-邻菲咯啉(L3)的氧钒配合物对PTP1B以及碱性磷酸酶(alkaline phosphatase,ALP)的体外抑制作用.结果表明,1∶1和2∶1型配位的氧钒化合物均表现出对PTP1B较强的抑制活性,IC50值在120～260nmol/L间,抑制能力接近双麦芽酚氧钒配合物(BMOV).抑制动力学实验表明这些氧钒配合物对PTP1B的抑制模式均为竞争性抑制,抑制常数在20～160nmol/L.其对PTP1B抑制活性较ALP高103倍,表明氧钒配合物对两种磷酸酶的抑制具有一定的选择性.
Protein tyrosine phosphatase 1B （PTP1B） has been emerging as an attractive drug target for diabetes disease treatment, and is also associated with the anti-diabetes effects of vanadium complexes. The inhibitory activities against PTP1B and alkaline phosphatase （ALP） by oxovanadium complexes with 2,2＇-biimidazole （L^1）, 2,2＇-bipyridine （L^2） and 1, 10-phenanthroline （L^3） have been investigated in vitro. The complexes of [VO（L^1-L^3）] and [VO（L^1-L^3）2] have been found to be potent inhibitors against PTP1B （IC50= 120-260 nmol/L）. Their inhibitory ability is close to bis（maltolato）oxovanadium （BMOV）. Kinetics assays suggest that these complexes inhibit PTP1B in a classical competitive manner （Ki=20-160 nmol/L）. The inhibitory activities of these complexes against PTP 1B are 103 fold higher than that against ALP, showing a selectivity against both phosphatases.
出处
《化学学报》
SCIE
CAS
CSCD
北大核心
2009年第9期929-936,共8页
Acta Chimica Sinica
基金
国家自然科学基金(No.20471033)
山西省自然科学基金(No.20051013)
山西省回国人员2008年科研资助项目
