DNA Enzymes Snip Amide Bonds

Chemists at the University of Illinois, Urbana-Champaign, have identified a deoxyribozyme that catalyzes amide hydrolysis, the first step toward making a DNA-based enzyme that can cleave proteins in specific places. Such a DNA enzyme could help researchers process proteins for proteomic studies. Scott K. Silverman and his team have been trying unsuccessfully to find an amide-hydrolyzing deoxyribozyme for years. Their first attempt yielded a DNA that performed phosphodiester cleavage instead. “There’s something about an amide bond that is difficult to cleave—at least by a nucleic acid catalyst,” Silverman says. Now, Silverman’s team has managed to produce DNA sequences that cleave amide bonds by incorporating modified nucleotides with amine, hydroxyl, or carboxyl groups (J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.5b12647). The modifications mimic the side chains on amino acids that are involved in peptide bond cleavage by natural proteases. “There’s a mechanistic basis for expecting some benefit from including these side