DNA catalysts with tyrosine kinase activity

J Am Chem Soc. 2013 Oct 9;135(40):14928-31. doi: 10.1021/ja407586u. Epub 2013 Sep 27.


We show that DNA catalysts (deoxyribozymes, DNA enzymes) can phosphorylate tyrosine residues of peptides. Using in vitro selection, we identified deoxyribozymes that transfer the γ-phosphoryl group from a 5'-triphosphorylated donor (a pppRNA oligonucleotide or GTP) to the tyrosine hydroxyl acceptor of a tethered hexapeptide. Tyrosine kinase deoxyribozymes that use pppRNA were identified from each of N30, N40, and N50 random-sequence pools. Each deoxyribozyme requires Zn(2+), and most additionally require Mn(2+). The deoxyribozymes have little or no selectivity for the amino acid identities near the tyrosine, but they are highly selective for phosphorylating tyrosine rather than serine. Analogous GTP-dependent DNA catalysts were identified and found to have apparent Km(GTP) as low as ∼20 μM. These findings establish that DNA has the fundamental catalytic ability to phosphorylate the tyrosine side chain of a peptide substrate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • DNA, Catalytic / metabolism*
  • Guanosine Triphosphate / metabolism
  • Oligonucleotides / metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • RNA / metabolism
  • Tyrosine / metabolism


  • DNA, Catalytic
  • Oligonucleotides
  • Tyrosine
  • RNA
  • Guanosine Triphosphate
  • Protein-Tyrosine Kinases