A DNA-conjugated small molecule catalyst enzyme mimic for site-selective ester hydrolysis.
A DNA-conjugated small molecule catalyst enzyme mimic for site-selective ester hydrolysis.
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DOI：
10.1039/c7sc04554a
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发表时间：
2018-02-28
期刊：
影响因子：
8.4
通讯作者：
Gorin DJ
中科院分区：
文献类型：
--
作者：
Flanagan ML;Arguello AE;Colman DE;Kim J;Krejci JN;Liu S;Yao Y;Zhang Y;Gorin DJ
设计用于模拟酶功能的DNA-咪唑缀合物位点选择性地水解靶酯，但不水解其它酯，与游离咪唑相比，具有>100倍的速率增强。在许多化学研究背景下，必须克服位点选择性的挑战，包括复杂天然产物的选择性功能化和生命系统中生物分子的标记。掺入分子识别结构域的合成催化剂可以模拟天然存在的酶以将化学反应引导至官能团的特定实例。我们认为，通过将小分子催化剂与DNA适体连接而制备的DNA缀合小分子催化剂（DCats）是一类很有前途的位点选择性转化试剂。具体地，开发了与等摩尔未束缚的咪唑相比能够将目标酯中的酯水解速率增加>100倍的DNA-咪唑缀合物。其他酯类不受影响。此外，DCat催化的水解遵循酶样动力学，并且DCat的刺激响应变体能够实现所需反应的可编程“开启”。
A DNA-imidazole conjugate, designed to mimic enzyme function, site-selectively hydrolyzes a target ester, but not other esters, with >100-fold rate enhancement compared to free imidazole. The challenge of site-selectivity must be overcome in many chemical research contexts, including selective functionalization in complex natural products and labeling of one biomolecule in a living system. Synthetic catalysts incorporating molecular recognition domains can mimic naturally-occurring enzymes to direct a chemical reaction to a particular instance of a functional group. We propose that DNA-conjugated small molecule catalysts (DCats), prepared by tethering a small molecule catalyst to a DNA aptamer, are a promising class of reagents for site-selective transformations. Specifically, a DNA-imidazole conjugate able to increase the rate of ester hydrolysis in a target ester by >100-fold compared with equimolar untethered imidazole was developed. Other esters are unaffected. Furthermore, DCat-catalyzed hydrolysis follows enzyme-like kinetics and a stimuli-responsive variant of the DCat enables programmable “turn on” of the desired reaction.
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