Laboratory of Bioinorganic Chemistry, Department of Chemistry , KU Leuven , Celestijnenlaan 200F , 3001 Leuven , Belgium.
Centre for Surface Chemistry and Catalysis , KU Leuven , Celestijnenlaan 200F , 3001 Leuven , Belgium.
J Am Chem Soc. 2018 May 23;140(20):6325-6335. doi: 10.1021/jacs.8b01902. Epub 2018 May 3.
MOF-808, a Zr(IV)-based metal-organic framework, has been proven to be a very effective heterogeneous catalyst for the hydrolysis of the peptide bond in a wide range of peptides and in hen egg white lysozyme protein. The kinetic experiments with a series of Gly-X dipeptides with varying nature of amino acid side chain have shown that MOF-808 exhibits selectivity depending on the size and chemical nature of the X side chain. Dipeptides with smaller or hydrophilic residues were hydrolyzed faster than those with bulky and hydrophobic residues that lack electron rich functionalities which could engage in favorable intermolecular interactions with the btc linkers. Detailed kinetic studies performed by H NMR spectroscopy revealed that the rate of glycylglycine (Gly-Gly) hydrolysis at pD 7.4 and 60 °C was 2.69 × 10 s ( t = 0.72 h), which is more than 4 orders of magnitude faster compared to the uncatalyzed reaction. Importantly, MOF-808 can be recycled several times without significantly compromising the catalytic activity. A detailed quantum-chemical study combined with experimental data allowed to unravel the role of the {ZrO} core of MOF-808 in accelerating Gly-Gly hydrolysis. A mechanism for the hydrolysis of Gly-Gly by MOF-808 is proposed in which Gly-Gly binds to two Zr(IV) centers of the {ZrO} core via the oxygen atom of the amide group and the N-terminus. The activity of MOF-808 was also demonstrated toward the hydrolysis of hen egg white lysozyme, a protein consisting of 129 amino acids. Selective fragmentation of the protein was observed with 55% yield after 25 h under physiological pH.
MOF-808 是一种基于 Zr(IV)的金属有机骨架，已被证明是一种非常有效的用于在广泛的肽和鸡卵清溶菌酶蛋白中水解肽键的多相催化剂。使用一系列具有不同氨基酸侧链性质的 Gly-X 二肽进行的动力学实验表明，MOF-808 表现出取决于 X 侧链的大小和化学性质的选择性。与具有大体积和疏水性残基的二肽相比，具有较小或亲水性残基的二肽的水解速度更快，因为这些残基缺乏可以与 btc 配体进行有利的分子间相互作用的富电子官能团。通过 H NMR 光谱进行的详细动力学研究表明，在 pD 7.4 和 60°C 下甘氨酰甘氨酸（Gly-Gly）的水解速率为 2.69×10 s（ t = 0.72 h），与未催化的反应相比，这快了 4 个数量级以上。重要的是，MOF-808 可以回收多次而不会显著降低催化活性。结合实验数据的详细量子化学研究揭示了 MOF-808 中{ZrO}核心在加速 Gly-Gly 水解中的作用。提出了 MOF-808 水解 Gly-Gly 的机理，其中 Gly-Gly 通过酰胺基团的氧原子和 N-末端与{ZrO}核心的两个 Zr(IV)中心结合。还证明了 MOF-808 对由 129 个氨基酸组成的鸡卵清溶菌酶的水解具有活性。在生理 pH 下反应 25 小时后，观察到蛋白质的选择性片段化，产率为 55%。
