Flanagan Moira L, Arguello A Emilia, Colman Drew E, Kim Jiyeon, Krejci Jesse N, Liu Shimu, Yao Yueyu, Zhang Yu, Gorin David J
Smith College , Department of Chemistry , Northampton , MA 01063 , USA . Email:
Chem Sci. 2018 Jan 15;9(8):2105-2112. doi: 10.1039/c7sc04554a. eCollection 2018 Feb 28.
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.
在许多化学研究领域中，必须克服位点选择性的挑战，包括复杂天然产物中的选择性官能团化以及生物系统中单个生物分子的标记。结合分子识别域的合成催化剂可以模仿天然存在的酶，将化学反应导向特定官能团实例。我们提出，通过将小分子催化剂与DNA适配体连接而制备的DNA共轭小分子催化剂（DCats）是一类有前途的用于位点选择性转化的试剂。具体而言，开发了一种DNA-咪唑共轭物，与等摩尔未连接的咪唑相比，它能够使目标酯中的酯水解速率提高100倍以上。其他酯不受影响。此外，DCat催化的水解遵循类酶动力学，并且DCat的刺激响应变体能够实现所需反应的可编程“开启”。
