TY - JOUR
T1 - DNA-Catalyzed Amide Hydrolysis
AU - Zhou, Cong
AU - Avins, Joshua L.
AU - Klauser, Paul C.
AU - Brandsen, Benjamin M.
AU - Lee, Yujeong
AU - Silverman, Scott K.
N1 - Funding Information:
This work was supported by a grant to S.K.S. from the National Institutes of Health (No. R01GM065966). B.M.B. was partially supported by NIH T32GM070421. We thank Yun Xie for technical assistance during the early stage of this work.
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/3/2
Y1 - 2016/3/2
N2 - 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.
AB - 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.
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U2 - 10.1021/jacs.5b12647
DO - 10.1021/jacs.5b12647
M3 - Article
C2 - 26854515
AN - SCOPUS:84959449584
VL - 138
SP - 2106
EP - 2109
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 7
ER -