Peptide Bond Hydrolysis Catalyzed by the Wells-Dawson Zr(α2-P2W17O61)2 Polyoxometalate
Peptide Bond Hydrolysis Catalyzed by the Wells-Dawson Zr(α2-P2W17O61)2 Polyoxometalate
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DOI：
10.1021/ic301364n
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发表时间：
2012-09-17
影响因子：
4.6
通讯作者：
Parac-Vogt, Tatjana N.
中科院分区：
文献类型：
--
作者：
Absillis, Gregory;Parac-Vogt, Tatjana N.
在本文中，我们报告的第一个例子，肽水解催化的聚氧乙烯复合物。合成了一系列金属取代的Wells-Dawson聚氧乙烯醚，并研究了它们对甘氨酰甘氨酸（GG）中的肽键的水解活性。其中Zr（IV）和Hf（IV）取代的杂多酸盐K15 H [Zr（alpha（2）-P2 W17 O 61）（2）]中心点25 H（2）O活性最高。进行了详细的动力学研究与锆（IV）取代，这是作为一种催化剂水解的肽键在GG。利用P-31 NMR谱研究了K15 H [Zr（alpha（2）-P2 W 17 O 61）（2）]中心点25 H（2）O的形态，并考察了其对GG水解速率的影响。在pD 5.0和60 ℃下观察到最高反应速率（k（obs）= 9.2（+/- 0.2）x 10（-5）min（-1））。在K15 H [Zr（alpha（2）-P2 W17 O 61）（2）]中心点25 H（2）O存在下水解10倍过量的GG，证明了催化原理。~（13）C NMR数据表明GG通过其N-端胺基和酰胺羰基氧与K_（15）H [Zr（alpha（2）-P_2W_（17）O_（61））（2）]中心点25 H（2）O中的Zr（IV）中心配位。K15 H [Zr（alpha（2）-P2 W17 O 61）（2）]中心点25 H（2）O对N-封闭类似物乙酰氨基甘氨酰甘氨酸的抑制作用以及草酸、苹果酸和柠檬酸的抑制作用证实了这些发现。三甘氨酸、四甘氨酸和五甘氨酸在K15 H [Zr（alpha（2）-P2 W17 O 61）（2）]中心点25 H（2）O存在下也完全水解，产生甘氨酸作为水解的最终产物。K15 H [Zr（alpha（2）-P2 W17 O 61）（2）]中心点25 H（2）O对一系列其它二肽也表现出水解活性。
In this paper we report the first example of peptide hydrolysis catalyzed by a polyoxometalate complex. A series of metal-substituted Wells-Dawson polyoxometalates were synthesized, and their hydrolytic activity toward the peptide bond in glycylglycine (GG) was examined. Among these, the Zr(IV)- and Hf(IV)-substituted ones were the most Wells-Dawson type polyoxometalate K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O reactive. Detailed kinetic studies were performed with the Zr(IV)-substituted which was shown to act as a catalyst for the hydrolysis of the peptide bond in GG. The speciation of K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O which is highly dependent on the pD, concentration, and temperature of the solution, was fully determined with the help of P-31 NMR spectroscopy and its influence on the GG hydrolysis rate was examined. The highest reaction rate (k(obs) = 9.2 (+/- 0.2) x 10(-5) min(-1)) was observed at pD 5.0 and 60 degrees C. A 10-fold excess of GG was hydrolyzed in the presence of K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O proving the principles of catalysis. C-13 NMR data suggested the coordination of GG to the Zr(IV) center in K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O via its N-terminal amine group and amide carbonyl oxygen. These findings were confirmed by the inactivity of K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O toward the N-blocked analogue acetamidoglycylglycinate and the inhibitory effect of oxalic, malic, and citric acid. Triglycine, tetraglycine, and pentaglycine were also fully hydrolyzed in the presence of K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O yielding glycine as the final product of hydrolysis. K15H[Zr(alpha(2)-P2W17O61)(2)]center dot 25H(2)O also exhibited hydrolytic activity toward a series of other dipeptides.