Schematic representation of a DNA double helix with metal-mediated base pairs
Schematic representation of a DNA double helix with metal-mediated base pairs
© J. Müller

Synthetic nucleic acids

The research focus of the Müller group is the bioinorganic chemistry of nucleic acids with a particular emphasis on the generation, characterization as well as application of nucleic acids including metal-mediated base pairs. Within a metal-mediated base pair, the hydrogen bonds between two complementary nucleobases are formally replaced by coordinate bonds to a central metal ion. The synthetic nucleic acid serves as template for the specific arrangement of metal ions along the helical axis. As this approach enables a site-specific arrangement of metal ions with high precision, interesting chemical and physical properties arise for the resulting constructs.

One of the main research areas is the development of new synthetic nucleosides for metal-mediated base pairs, thus combining metal-based functionality with the evolutionary optimized, reversible self-assembly of nucleic acids. For example, we succeeded in the generation of a metal-mediated base pair including two metal ions and, for that reason, exhibiting luminescent properties. An additional focus is the development of applications based on metal-modified nucleic acids. Possible applications are sensors for various analytes, supramolecular networks with metal-based functionality, catalysts in asymmetric catalysis and many more. We developed a nucleic acid that is able to recognize via metal-mediated base pair formation one oligonucleotide from a mixture of natural oligonucleotides that differ by a single nucleoside only. Moreover, our synthetic nucleic acids including artificial ligand-based nucleosides can be applied for a controlled aggregation of DNA to form supramolecular structures. A further application is the generation of DNA-stabilized metal nanoclusters.

Relevant preliminary work:

  1. Stable Cu(I)-Mediated Base Pairing in DNA
    Jash B, Müller J, Angew. Chem. Int. Ed. 57, 9524-9527 (2018)
  2. A metal-mediated base pair that discriminates between the canonical pyrimidine nucleobases
      Jash B, Scharf P, Sandmann N, Fonseca Guerra C, Megger D A, Müller J. Chem. Sci. 8, 1337-1343 (2017)
  3. Solution structure of a DNA double helix with consecutive metal-mediated base pairs
    Johannsen S, Megger N, Böhme D, Sigel R K O, Müller J. Nat. Chem. 2, 229-234 (2010)