DNA-Catalyzed Amide Hydrolysis
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- 作者：Cong Zhou ; Joshua L. Avins ; Paul C. Klauser ; Benjamin M. Brandsen ; Yujeong Lee ; Scott K. Silverman
- 刊名：Journal of the American Chemical Society
- 出版年：2016
- 出版时间：February 24, 2016
- 年：2016
- 卷：138
- 期：7
- 页码：2106-2109
- 全文大小：323K
- ISSN：1520-5126
文摘
DNA catalysts (deoxyribozymes) for a variety of reactions have been identified by in vitro selection. However, for certain reactions this identification has not been achieved. One important example is DNA-catalyzed amide hydrolysis, for which a previous selection experiment instead led to DNA-catalyzed DNA phosphodiester hydrolysis. Subsequent efforts in which the selection strategy deliberately avoided phosphodiester hydrolysis led to DNA-catalyzed ester and aromatic amide hydrolysis, but aliphatic amide hydrolysis has been elusive. In the present study, we show that including modified nucleotides that bear protein-like functional groups (any one of primary amino, carboxyl, or primary hydroxyl) enables identification of amide-hydrolyzing deoxyribozymes. In one case, the same deoxyribozyme sequence without the modifications still retains substantial catalytic activity. Overall, these findings establish the utility of introducing protein-like functional groups into deoxyribozymes for identifying new catalytic function. The results also suggest the longer-term feasibility of deoxyribozymes as artificial proteases.