DNA-Catalyzed Amide Hydrolysis

J Am Chem Soc. 2016 Feb 24;138(7):2106-9. doi: 10.1021/jacs.5b12647. Epub 2016 Feb 15.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amides / chemistry*
  • Catalysis
  • DNA / chemistry*
  • Hydrolysis

Substances

  • Amides
  • DNA