| 生物小分子钒配合物抑制蛋白酪氨酸磷酸酶活性研究 |
| PTPs Inhibition by Some Oxovanadium Complexes with Bioligands |
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| 摘要: 钒化合物治疗糖尿病机理研究表明其与蛋白酪氨酸磷酸酶的酶活抑制有一定关系。本文分别研究了生物小分子配体与氧钒离子在20:1配比条件下形成的生物小分子钒配合物及其对蛋白酪氨酸磷酸酶的抑制作用和选择性。结果表明氨基酸与氧钒离子配合形成2:1的配合物,而抗坏血酸及多羧酸与氧钒离子配合形成1:1的配合物。它们对蛋白酪氨酸磷酸酶抑制作用显示,大部分生物小分子氧钒配合物对PTP1B表现强烈的抑制作用,IC50值在0.12~0.63 μmol·L-1之间。化合物[VO(Phe)2]表现最强的抑制作用,IC50值为0.07 μmol·L-1。而[VO(Arg)2]、[VO(Oxalate)]、[VO(Nitrilotriacetate)]和[VO(Citrate)]则呈现较弱的抑制,IC50值分别为1.05、1.41、9.90和21.5 μmol·L-1。对PTP1B, TCPTP, HePTP以及SHP-1的抑制作用表明配体的结构不仅影响氧钒配合物对蛋白酪氨酸磷酸酶的抑制效率同时也影响其选择性。 |
| 关键词: 生物小分子 钒配合物 蛋白酪氨酸磷酸酶 抑制 选择性 |
| 基金项目: 国家自然科学基金(No.21171109);山西省自然科学基金(2011011009-1);山西省回国留学人员科研课题(2012-004)资助项目。 |
| Abstract: The inhibition of PTPs which dephosphorylate the insulin receptor, resulting in prolongation of insulin signaling, is involved in the mechanism of vanadiums insulin-sensitizing effects. Here, the speicies of vanadium complexes in the solution with bioligands to oxovanadium ions of 20:1 molar ratio are investigated by UV-Vis spectra, and their inhibition over protein tyrosine phosphatases are evaluated. The results show that in the solution, amino acids are coordinated to oxovanadium ions to form 2:1 vanadium complexes, but ascorbic acid, citric acid, iminodiacetic acid and malic acid form 1:1 vanadium complexes. The inhibitions against protein tyrosine phosphatases indicate among 19 systems of 20:1 molar ratio of bioligands to VO(Ⅱ), 14 systems exhibit strong inhibition over PTP1B (protein tyrosine phosphatase 1B) with IC50 of 0.12~0.63 μmol·L-1, and[VO(Phe)2] system displays strongest inhibition with IC50 of 0.07 μmol·L-1 while[VO(Arg)2],[VO(Oxalate)],[VO(Nitrilotriacetate] and[VO(Citrate)] systems show weaker inhibition with IC50 about 1.05, 1.41, 9.90 and 21.5 μmol·L-1, respectively. The selectivity of[VO(Arg)2],[VO(Tyr)2],[VO(Phe)2],[VO(Malate)],[VO(Lactate)] and[VO(Citrate)] systems over PTP1B, TCPTP (T-cell protein tyrosine phosphatase), HePTP (Hematopoietic protein tyrosine phosphatase) and SHP-1 (Src homology phosphatase 1) show the inhibitions against four PTPs are varied with the change of the bioligands, suggesting the structures of the bioligands influence the potency of the PTPs inhibition and the selectivity. |
| Keywords: bioligands oxovanadium complexs protein tyrosine phosphatase (PTP) inhibition selectivity |
| 投稿时间：2013-01-14 修订日期：2013-03-22 |
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| 李鹏宇,卢丽萍.生物小分子钒配合物抑制蛋白酪氨酸磷酸酶活性研究[J].无机化学学报,2013,29(9):1830-1834. |
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