Research

Overview    |    Protein Modification Reactions    |    DNA Substrate Reactions    |    Small-Molecule Reactions    |    RNA Ligation    |    Funding

DNA-Catalyzed DNA Hydrolysis & Other Reactions of DNA Substrates

We showed that DNA has the remarkable ability to catalyze hydrolysis of DNA phosphodiester bonds with useful sequence- and site-selectivities. Although the uncatalyzed hydrolysis reaction has a half-life of 30 million years, one deoxyribozyme functions with a half-life of merely 15 minutes. This translates to a DNA-catalyzed rate enhancement of 1012, subsequently improved to 3 x 1013 upon reselection. We are also studying deoxyribozymes that catalyze other reactions of DNA substrates, such as N-acylation and N-alkylation of oligonucleotide nucleobases.

Representative Publications

  • "DNAzyme-Catalyzed Site-Specific N-Acylation of DNA Oligonucleotide Nucleobases", M. M. Kennebeck, C. K. Kaminsky, M. A. Massa, P. K. Das, R. D. Boyd, M. Bishka, J. T. Tricarico, and S. K. Silverman, Angew. Chem. Int. Ed. 2024, 63, e202317565. [pdf] [Supp Info] [PubMed entry]
  • "DNA-Catalyzed DNA Cleavage by a Radical Pathway with Well-Defined Products", Y. Lee, P. C. Klauser, B. M. Brandsen, C. Zhou, X. Li, and S. K. Silverman,
    J. Am. Chem. Soc. 2017, 139, 255-261. [pdf] [PubMed entry]
  • "DNA Oligonucleotide 3'-Phosphorylation Catalyzed by a DNA Enzyme", A. J. Camden, S. M. Walsh, S. H. Suk, and S. K. Silverman, Biochemistry 2016, 55, 2671-2676. [pdf] [Supp Info] [PubMed entry]
  • "DNA Catalysis of a Normally Disfavored RNA Hydrolysis Reaction", D. J. Parker, Y. Xiao, J. M. Aguilar, and S. K. Silverman, J. Am. Chem. Soc. 2013, 135, 8472-8475. [pdf] [Supp Info] [PubMed entry]
  • "Systematic Evaluation of the Dependence of Deoxyribozyme Catalysis on Random Region Length", T. E. Velez, J. Singh, Y. Xiao, E. C. Allen, O. Y. Wong, M. Chandra, S. C. Kwon, and S. K. Silverman, ACS Comb. Sci. 2012, 14, 680-687. [pdf] [Supp Info] [PubMed entry]
  • "Lanthanide Ions as Required Cofactors for DNA Catalysts", V. Dokukin and S. K. Silverman, Chem. Sci. 2012, 3, 1707-1714. [pdf] [Supp Info] [PubMed entry]
  • "Establishing Broad Applicability of DNA Catalysts for Site-Specific DNA Hydrolysis", Y. Xiao, R. J. Wehrmann, N. A. Ibrahim, and S. K. Silverman, Nucleic Acids Res. 2012, 40, 1778-1786. [pdf] [Supp Info] [PubMed entry]
  • "Merely Two Mutations Switch a DNA-Hydrolyzing Deoxyribozyme from Heterobimetallic (Zn2+/Mn2+) to Monometallic (Zn2+-only) Behavior", Y. Xiao, E. C. Allen, and S. K. Silverman, Chem. Commun. 2011, 47, 1749-1751. [pdf] [Supp Info] [PubMed entry]
  • "Functional Compromises Among pH Tolerance, Site Specificity, and Sequence Tolerance for a DNA-Hydrolyzing Deoxyribozyme", Y. Xiao, M. Chandra, and S. K. Silverman, Biochemistry 2010, 49, 9630-9637. [pdf] [Supp Info] [PubMed entry]
  • "DNA-Catalyzed Sequence-Specific Hydrolysis of DNA", M. Chandra, A. Sachdeva, and S. K. Silverman, Nature Chem. Biol. 2009, 5, 718-720. [pdf] [Supp Info] [PubMed entry] [Nature Chemical Biology News & Views article]