We previously reported that DNA catalysts (deoxyribozymes) can hydrolyze DNA phosphodiester linkages, but DNA-catalyzed amide bond hydrolysis has been elusive, despite having a much shorter uncatalyzed half-life of hydrolysis compared to a phosphodiester bond. Here we used in vitro selection to identify DNA catalysts that hydrolyze ester linkages as well as DNA catalysts that hydrolyze aromatic amides, for which the leaving group is an aniline moiety. The aromatic amide-hydrolyzing deoxyribozymes were examined using linear free energy relationship analysis, revealing that the hydrolysis reaction is accelerated by electron-donating groups on the aromatic ring and indicating rate-determining proton-transfer to the anilide nitrogen atom after the addition step of the addition-elimination hydrolysis mechanism. These results establish that DNA has the catalytic ability to achieve hydrolysis of esters and amides as carbonyl-based substrates. The difficulty in identifying deoxyribozymes that hydrolyze aliphatic amide bonds suggests that an alternative to hydrolysis may be required to achieve DNA-catalyzed peptide bond cleavage.

DNA-catalyzed hydrolysis of esters and aromatic amides

246th National Meeting (2013)

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