Institute of Molecular Science, the Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Shanxi University, Taiyuan, 030006, China.
J Inorg Biochem. 2011 Sep;105(9):1138-47. doi: 10.1016/j.jinorgbio.2011.05.015. Epub 2011 May 27.
Three dinuclear copper complexes of organic claw ligands (2,2',2″,2'''-(5-R-2-hydroxy-1,3-phenylene)bis(methylene)bis(azanetriyl)tetraacetic acid, R=methyl (H(5)L1), chloro (H(5)L2) and bromo (H(5)L3)): [Cu(2)NaL1(H(2)O)(2)] (1), [Cu(2)HL2(H(2)O)(2)] (2), [Cu(2)NaL3(H(2)O)(2)] (3), have been synthesized and characterized by elemental analyses, infrared spectra, thermo-gravimetric analyses, X-ray diffraction analysis, electrospray ionization mass spectra, pH-potentiometric titration, molar conductivity. Their inhibitory effects against human protein tyrosine phosphatase 1B (PTP1B), T cell protein tyrosine phosphatase (TCPTP), Megakaryocyte protein tyrosinephosphatase 2 (PTP-MEG2), srchomology phosphatase 1 (SHP-1) and srchomology phosphatase 2 (SHP-2) are evaluated in vitro. The three copper complexes exhibit potent and almost same inhibition against PTP1B and SHP-1 with IC(50) values ranging from 0.15 to 0.31μM, about 2-fold stronger inhibition than against PTP-MEG2, 10-fold stronger inhibition than against TCPTP, but almost no inhibition against SHP-2. Kinetic analysis indicates that they are reversible competitive inhibitors of PTP1B. Molecular docking analyses confirm the inhibition model. Fluorescence titration studies suggest that the complexes bond to PTP1B with the formation of a 1:1 complex. The results demonstrate that copper complexes that are potent PTPs inhibitors but have different inhibitory effects over different PTPs, may be explored as new practical inhibitors towards individual PTP with some specificity.
三种双核铜配合物的有机爪配体（2,2',2″,2'''-(5-R-2-羟基-1,3-亚苯基)双亚甲基双（氮杂三乙撑）四乙酸，R=甲基（H(5)L1)，氯（H(5)L2)和溴（H(5)L3))：[Cu(2)NaL1(H(2)O)(2)] (1)，[Cu(2)HL2(H(2)O)(2)] (2)，[Cu(2)NaL3(H(2)O)(2)] (3)，通过元素分析、红外光谱、热重分析、X 射线衍射分析、电喷雾电离质谱、pH-电位滴定、摩尔电导率进行了合成和表征。它们对人蛋白酪氨酸磷酸酶 1B（PTP1B）、T 细胞蛋白酪氨酸磷酸酶（TCPTP）、巨核细胞蛋白酪氨酸磷酸酶 2（PTP-MEG2）、srchomology 磷酸酶 1（SHP-1）和 srchomology 磷酸酶 2（SHP-2）的体外抑制作用进行了评价。三种铜配合物对 PTP1B 和 SHP-1 的抑制作用非常强，IC(50)值在 0.15 到 0.31μM 之间，比 PTP-MEG2 强 2 倍，比 TCPTP 强 10 倍，但对 SHP-2 几乎没有抑制作用。动力学分析表明它们是 PTP1B 的可逆竞争性抑制剂。分子对接分析证实了抑制模型。荧光滴定研究表明，这些配合物与 PTP1B 结合形成 1:1 复合物。结果表明，对不同 PTP 具有不同抑制作用的强效 PTP 抑制剂铜配合物，可能会被探索为针对个别 PTP 具有一定特异性的新型实用抑制剂。
