Research

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

Covalent Modification of Proteins by DNA Catalysts

Catalyzing the covalent modification of protein side chains is a difficult yet important goal. Protein side chain modifications of many kinds have tremendous biological importance. However, the chemical tools currently available for synthesizing proteins that have side chain modifications are limited and often tedious. We have shown that DNA has the fundamental capacity to catalyze several biologically relevant reactions of side chains such as tyrosine, serine, and lysine, and we are working to expand the context of this DNA-catalyzed reactivity. In other efforts, we are pursuing DNA-catalyzed peptide bond cleavage, with the ultimate aim of developing protease deoxyribozymes that have useful amino acid sequence selectivities.

Representative Publications

  • "Defining the Substrate Scope of DNAzyme Catalysis for Reductive Amination with Aliphatic Amines", S. Yang and S. K. Silverman, Org. Biomol. Chem. 2023, 21, 1910-1919. [pdf] [Supp Info] [PubMed entry]
  • "DNAzymes for Amine and Peptide Lysine Acylation", T. Yao, J. J. Przybyla, P. Yeh, A. M. Woodard, H. J. Nilsson, B. M. Brandsen, and S. K. Silverman, 2021, 19, 171-181. [pdf] [Supp Info] [PubMed entry]
  • "DNA-Catalyzed Introduction of Azide at Tyrosine for Peptide Modification", P. Wang and S. K. Silverman, Angew. Chem. Int. Ed. 2016, 55, 10052-10056. [pdf] [Supp Info] [PubMed entry]
  • "Assessing Histidine Tags for Recruiting Deoxyribozymes to Catalyze Peptide and Protein Modification Reactions", C. Chu and S. K. Silverman, Org. Biomol. Chem. 2016, 14, 4697-4703. [pdf] [Supp Info] [PubMed entry]
  • "DNA-Catalyzed Amide Hydrolysis", C. Zhou, J. L. Avins, P. C. Klauser, B. M. Brandsen, Y. Lee, and S. K. Silverman, J. Am. Chem. Soc. 2016, 138, 2106-2109. [pdf] [Supp Info] [PubMed entry]
  • "Identification of Sequence-Selective Tyrosine Kinase Deoxyribozymes", S. M. Walsh, S. N. Konecki, and S. K. Silverman, J. Mol. Evol. 2015, 81, 218-224. [pdf] [PubMed entry]
  • "Phosphoserine Lyase Deoxyribozymes: DNA-Catalyzed Formation of Dehydroalanine Residues in Peptides", J. Chandrasekar, A. C. Wylder, and S. K. Silverman, J. Am. Chem. Soc. 2015, 137, 9575-9578. [pdf] [Supp Info] [PubMed entry]
  • "A Modular Tyrosine Kinase Deoxyribozyme with Discrete Aptamer and Catalyst Domains", V. Dokukin and S. K. Silverman, Chem. Commun. 2014, 50, 9317-9320. [pdf] [Supp Info] [PubMed entry]
  • "DNA-Catalyzed Lysine Side Chain Modification", B. M. Brandsen, T. E. Velez, A. Sachdeva, N. A. Ibrahim, and S. K. Silverman, Angew. Chem. Int. Ed. 2014, 53, 9045-9050. [pdf] [Supp Info] [PubMed entry]
  • "A Generalizable DNA-Catalyzed Approach to Peptide-Nucleic Acid Conjugation", C. Chu, O. Wong, and S. K. Silverman, ChemBioChem 2014, 15, 1905-1910. [pdf] [Supp Info] [PubMed entry]
  • "DNA-Catalyzed Hydrolysis of Esters and Aromatic Amides", B. M. Brandsen, A. R. Hesser, M. A. Castner, M. Chandra, and S. K. Silverman, J. Am. Chem. Soc. 2013, 135, 16014-16017. [pdf] [Supp Info] [PubMed entry]
  • "DNA Catalysts with Tyrosine Kinase Activity", S. M. Walsh, A. Sachdeva, and S. K. Silverman, J. Am. Chem. Soc. 2013, 135, 14928-14931. [pdf] [Supp Info] [PubMed entry]
  • "Catalytic DNA with Phosphatase Activity", J. Chandrasekar and S. K. Silverman, Proc. Natl. Acad. Sci. USA 2013, 110, 5315-5320. [pdf] [Supp Info] [PubMed entry] [UIUC press release]
  • "Systematic Evaluation of the Dependence of Deoxyribozyme Catalysis on Random Region Length", T. E. Velez, J. Singh, Y. Xiao, E. C. Allen, O. Wong, M. Chandra, S. C. Kwon, and S. K. Silverman, ACS Comb. Sci. 2012, 14, 680-687. [pdf] [Supp Info] [PubMed entry]
  • "Covalent Tagging of Phosphorylated Peptides by Phosphate-Specific Deoxyribozymes", A. Sachdeva, M. Chandra, J. Chandrasekar, and S. K. Silverman, ChemBioChem 2012, 13, 654-657. [pdf] [Supp Info] [PubMed entry]
  • "DNA-Catalyzed Reactivity of a Phosphoramidate Functional Group and Formation of an Unusual Pyrophosphoramidate Linkage", A. Sachdeva and S. K. Silverman, Org. Biomol. Chem. 2012, 10, 122-125. [pdf] [Supp Info] [PubMed entry]
  • "DNA-Catalyzed Reductive Amination", O. Wong, A. E. Mulcrone, and S. K. Silverman, Angew. Chem. Int. Ed. 2011, 50, 11679-11684. [pdf] [Supp Info] [PubMed entry]
  • "DNA-Catalyzed Covalent Modification of Amino Acid Side Chains in Tethered and Free Peptide Substrates", O. Wong, P. I. Pradeepkumar, and S. K. Silverman, Biochemistry 2011, 50, 4741-4749. [pdf] [Supp Info] [PubMed entry]
  • "DNA-Catalyzed Serine Side Chain Reactivity and Selectivity", A. Sachdeva and S. K. Silverman, Chem. Commun. 2010, 46, 2215-2217. [pdf] [Supp Info] [PubMed entry] [Chem. Commun. "Hot Article" feature story]
  • "DNA-Catalyzed Formation of Nucleopeptide Linkages", P. I. Pradeepkumar, C. Höbartner, D. A. Baum, and S. K. Silverman, Angew. Chem. Int. Ed. 2008, 47, 1753-1757. [pdf] [Supp Info] [PubMed entry]