Catalytic Hydrolysis of Adenosine Triphosphate (ATP) by Antitumoral epsilon-Keggin Core Compound, [H2MoV12O28(OH)12(MoVIO3)4]6-, at pH 5 and pH 7.5
Catalytic Hydrolysis of Adenosine Triphosphate (ATP) by Antitumoral epsilon-Keggin Core Compound, [H2MoV12O28(OH)12(MoVIO3)4]6-, at pH 5 and pH 7.5
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抗肿瘤 epsilon-Keggin 核心化合物 [H2MoV12O28(OH)12(MoVIO3)4]6- 在 pH 5 和 pH 7.5 下催化三磷酸腺苷 (ATP) 水解
DOI：
10.1002/ejic.201201164
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发表时间：
2013
影响因子：
2.3
通讯作者：
Toshihiro Yamase
中科院分区：
文献类型：
--
作者：
Eri Ishikawa;Toshihiro Yamase
用31P核磁共振波谱、电喷雾电离质谱仪(ESI-MS)和等温滴定量热法(ITC)研究了抗肿瘤化疗候选化合物[Me_3NH]_6[H_2MoV_(12)O_(28)(OH)_(12)(MoV_2O_3)_4]·2H_2O(PM-17)在40℃下催化三磷酸腺苷(ATP)[生成腺苷二磷酸(ADP)和磷酸盐]的反应。在pH值为5和7.5的条件下，三磷酸腺苷在催化作用下生成ADP、HnPO4(3-n)-、腺苷一磷酸(AMP)和[(PO4)2Mo5O15]6-。AMP和[(PO4)2Mo5O15]6-是ATP水解的第二步产物：前者是由ADP的水解(伴随着磷酸盐的释放)产生的，后者是由磷酸盐和单钼酸盐之间的缩合产生的(来自PM-17阴离子的MoVIO3部分的部分释放)。通过K+与带负电荷的三磷酸腺苷中的Pγ磷酸的静电相互作用，讨论了K+对三磷酸腺苷水解的促进作用，这种相互作用伴随着PM-17阴离子的配位和该磷酸的构象限制。在pH 7.5时，三磷酸腺苷与PM-17相互作用的热力学参数表明，K+介导PM-17阴离子在5‘-三磷酸链上组装(基质效应)，这导致由于Pγ-O-Pβ键被抑制而导致三磷酸腺苷的水解率降低。
The hydrolysis of adenosine triphosphate (ATP) [to adenosine diphosphate (ADP) and phosphate] at 40 °C by [Me3NH]6[H2MoV12O28(OH)12(MoVIO3)4]·2H2O (PM‐17) as an important candidate for antitumor chemotherapy is investigated with the help of31P NMR spectroscopy, electrospray ionization mass spectrometry (ESI‐MS), and isothermal titration calorimetry (ITC). The ATP hydrolysis at pH 5 and 7.5 proceeds catalytically to yield ADP, HnPO4(3–n)–, adenosine monophosphate (AMP), and [(PO4)2Mo5O15]6–. AMP and [(PO4)2Mo5O15]6–result from the secondary step of the ATP hydrolysis: the former was produced by the hydrolysis of ADP (with the liberation of phosphate), and the latter by the condensation among phosphates and monomolybdates (derived from the partial release of the MoVIO3moieties from the PM‐17 anion). The enhancement of the ATP hydrolysis in the presence of K+is discussed in terms of the electrostatic interaction of K+at the Pγphosphate in the negatively charged ATP 5′‐triphosphates, which accompanies the coordination of PM‐17 anions with a resultant conformational constraint of this phosphate. Values of thermodynamic parameters for the interaction between ATP and PM‐17 at pH 7.5 suggest the K+‐mediated assembly of PM‐17 anions at the 5′‐triphosphate chain (matrix effect), which leads to a decrease in the ATP hydrolysis owing to the depressed activation of the Pγ–O–Pβlinkage.