posted on 2013-10-30, 00:00authored byBenjamin
M. Brandsen, Anthony R. Hesser, Marissa A. Castner, Madhavaiah Chandra, Scott K. Silverman
We
previously reported that DNA catalysts (deoxyribozymes) can
hydrolyze DNA phosphodiester linkages, but DNA-catalyzed amide bond
hydrolysis has been elusive. 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. The hydrolysis
reaction is unaffected by substituents on the aromatic ring (ρ
≈ 0), suggesting general acid-catalyzed elimination as the
likely rate-determining step of the addition–elimination hydrolysis
mechanism. These findings establish that DNA has the catalytic ability
to achieve hydrolysis of esters and aromatic amides as carbonyl-based
substrates, and they suggest a mechanism-based approach to achieve
DNA-catalyzed aliphatic amide hydrolysis.