Carbonic anhydrase mimics with rationally designed active sites for fine-tuned catalytic activity and selectivity in ester hydrolysis.
Carbonic anhydrase mimics with rationally designed active sites for fine-tuned catalytic activity and selectivity in ester hydrolysis.
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DOI：
10.1039/d3cy00704a
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发表时间：
2023-10-02
影响因子：
5
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中科院分区：
文献类型：
--
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许多水解酶利用锌作为催化的辅因子。我们在这里报道了在活性部位和附近的碱基上含有锌离子的水溶性聚合物纳米颗粒，作为碳酸酐酶(CA)的模拟物。他们对锌结合水的pKa为6.3-6.4，低于天然酶的6.8-7.3，这允许催化剂在中性条件下水解未活化的烷基酯-这是人工酯酶长期以来追求的目标。活性中心的大小和形状可以通过分子印迹中使用的模板进行合理的调节。模板中细微的结构变化，包括乙基移动一个C-N键和亚甲基的去除，与催化活性直接相关。通过模板的模块化合成，可以使催化剂具有高度专一性或具有广泛的底物专一性。合成的碳酸酐酶模拟物显示锌结合水的pKa值低于天然酶。因此，它能够在pH为7的条件下对未活化的酯进行水解性研究。
Numerous hydrolytic enzymes utilize zinc as a cofactor for catalysis. We here report water-soluble polymeric nanoparticles with zinc ions in active sites and a nearby base as a mimic of carbonic anhydrase (CA). Their pKa of 6.3–6.4 for zinc-bound water is lower than the 6.8–7.3 value for natural enzymes, which allows the catalyst to hydrolyze nonactivated alkyl esters under neutral conditions—a long sought-after goal for artificial esterases. The size and shape of the active site can be rationally tuned through a template used in molecular imprinting. Subtle structural changes in the template, including shifting an ethyl group by one C–N bond and removal of a methylene group, correlate directly with catalytic activity. A catalyst can be made to be highly specific or have broad substrate specificity through modular synthesis of templates. A synthetic mimic of carbonic anhydrase shows a lower pKa value for the zinc-bound water than the natural enzyme. As a result, it is able to hydrolyze nonactivated esters at pH 7.
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影响因子：
15
作者：
JENCKS, WP;CARRIUOLO, J
通讯作者：
CARRIUOLO, J
影响因子：
12.9
作者：
Bose, Ishani;Zhao, Yan
通讯作者：
Zhao, Yan
影响因子：
15
作者：
BENDER, ML;NEVEU, M;POLLOCK, EJ
通讯作者：
POLLOCK, EJ
影响因子：
6.7
作者：
Al-Garawi, Z. S.;McIntosh, B. A.;Serpell, L. C.
通讯作者：
Serpell, L. C.
影响因子：
21.8
作者：
Burton, Antony J.;Thomson, Andrew R.;Woolfson, Derek N.
通讯作者：
Woolfson, Derek N.