Department of Chemistry, KU Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
Inorg Chem. 2012 Sep 17;51(18):9902-10. doi: 10.1021/ic301364n. Epub 2012 Aug 28.
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 reactive. Detailed kinetic studies were performed with the Zr(IV)-substituted Wells-Dawson type polyoxometalate K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O which was shown to act as a catalyst for the hydrolysis of the peptide bond in GG. The speciation of K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O which is highly dependent on the pD, concentration, and temperature of the solution, was fully determined with the help of (31)P NMR spectroscopy and its influence on the GG hydrolysis rate was examined. The highest reaction rate (k(obs) = 9.2 (±0.2) × 10(-5) min(-1)) was observed at pD 5.0 and 60 °C. A 10-fold excess of GG was hydrolyzed in the presence of K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O proving the principles of catalysis. (13)C NMR data suggested the coordination of GG to the Zr(IV) center in K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O via its N-terminal amine group and amide carbonyl oxygen. These findings were confirmed by the inactivity of K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·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 K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O yielding glycine as the final product of hydrolysis. K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O also exhibited hydrolytic activity toward a series of other dipeptides.
在本文中，我们报道了首例由多金属氧酸盐配合物催化的肽水解反应。我们合成了一系列金属取代的 Wells-Dawson 多金属氧酸盐，并研究了它们对甘氨酰甘氨酸（GG）肽键的水解活性。其中，Zr(IV)和 Hf(IV)取代的多金属氧酸盐最具反应活性。我们使用 Zr(IV)取代的 Wells-Dawson 型多金属氧酸盐 K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O 进行了详细的动力学研究，该化合物可作为 GG 肽键水解的催化剂。在 pH 值、浓度和温度的影响下，K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O 的形态完全通过 (31)P NMR 光谱确定，并研究了其对 GG 水解速率的影响。在 pH 值为 5.0 和 60°C 时，观察到最高的反应速率（k(obs) = 9.2 (±0.2) × 10(-5) min(-1)）。在 K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O 的存在下，10 倍过量的 GG 被水解，证明了催化原理。(13)C NMR 数据表明，GG 通过其 N-末端胺基和酰胺羰基氧与 K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O 中的 Zr(IV)中心配位。这些发现得到了 K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O 对 N-封闭类似物乙酰氨基甘氨酰甘氨酸无活性以及草酸、苹果酸和柠檬酸的抑制作用的证实。三肽、四肽和五肽也在 K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O 的存在下完全水解，生成甘氨酸作为水解的最终产物。K(15)H[Zr(α(2)-P(2)W(17)O(61))(2)]·25H(2)O 对一系列其他二肽也表现出水解活性。
