Efficient Synthesis of Peptide and Protein Functionalized Pyrrole-Imidazole Polyamides Using Native Chemical Ligation

Int J Mol Sci. 2015 Jun 4;16(6):12631-47. doi: 10.3390/ijms160612631.


The advancement of DNA-based bionanotechnology requires efficient strategies to functionalize DNA nanostructures in a specific manner with other biomolecules, most importantly peptides and proteins. Common DNA-functionalization methods rely on laborious and covalent conjugation between DNA and proteins or peptides. Pyrrole-imidazole (Py-Im) polyamides, based on natural minor groove DNA-binding small molecules, can bind to DNA in a sequence specific fashion. In this study, we explore the use of Py-Im polyamides for addressing proteins and peptides to DNA in a sequence specific and non-covalent manner. A generic synthetic approach based on native chemical ligation was established that allows efficient conjugation of both peptides and recombinant proteins to Py-Im polyamides. The effect of Py-Im polyamide conjugation on DNA binding was investigated by Surface Plasmon Resonance (SPR). Although the synthesis of different protein-Py-Im-polyamide conjugates was successful, attenuation of DNA affinity was observed, in particular for the protein-Py-Im-polyamide conjugates. The practical use of protein-Py-Im-polyamide conjugates for addressing DNA structures in an orthogonal but non-covalent manner, therefore, remains to be established.

Keywords: DNA-functionalization; DNA-nanotechnology; native chemical ligation; pyrrole-imidazole polyamides; surface plasmon resonance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry*
  • DNA / metabolism
  • Imidazoles / chemistry
  • Molecular Structure
  • Nylons / chemical synthesis*
  • Nylons / chemistry
  • Peptides / chemistry
  • Peptides / metabolism*
  • Pyrroles / chemistry
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism*
  • Surface Plasmon Resonance


  • Imidazoles
  • Nylons
  • Peptides
  • Pyrroles
  • Recombinant Proteins
  • imidazole
  • DNA