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THE HÖBARTNER GROUP: ORGANIC AND BIOMOLECULAR CHEMISTRY

Research Topics

The current research projects in the Höbartner group address the following scientific topics:

  • Chemical biology of natural RNA modifications: detection and quantitative analysis, design and synthesis of spectroscopic and mechanistic probes
  • Functional nucleic acids: in vitro evolution of ribozymes, deoxyribozymes and aptamers with small molecule cofactors, fluorogenic RNA aptamers, methyltransferase ribozymes
  • Expanding the scope of DNA/RNA-catalyzed reactions for RNA labelling and visualization
  • Structures of DNA and RNA enzymes, mechanisms of nucleic acid catalysis
  • Supramolecular chemistry with nucleic acid building blocks
  • Modified nucleotides and oligonucleotides with therapeutic potential

 

Ribozymes with new catalytic functions

In vitro selection from random libraries enables the discovery of new RNA catalysts. We discovered the first methyl transferase ribozyme (MTR1) and develop ribozymes for site-specific labeling of RNA with fluorescent nucleotides. 

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DNA as a catalyst

Deoxyribozymes are enzymes made of DNA that are generated in the laboratory by in vitro selection. We develop  RNA-cleaving DNAzymes for the detection of native RNA modifications. Earlier we solved the first structure of an RNA-ligating deoxyribozyme.

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Light up your RNA

The fluorogenic RNA aptamer named Chili activates fluorescence of a small molecule ligand. The structure was solved by x-ray crystallogrpahy. The mechanism of fluorescence activation involves excited state proton transfer (ESPT) to the RNA.

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Supramolecular nucleic acid chemistry

The programmable nature of Watson-Crick base pairing makes DNA and RNA versatile building blocks for the assembly of larger supramolecular structures. We explore nucleic acids in combination with artificial backbones (XNA) for the incorporation and defined spatial organization of chromophores to generate hybrid materials.

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Chemical synthesis of RNA

Natural RNA is not limited to the four letters A, C, G, and U, but contains more than 150 different modified nucleotides with diverse biological roles. We synthesize RNA with various modification patterns to elucidate biosynthetic pathways and cellular functions of modified RNA. 

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Nucleosides and oligonucleotides

Chemically synthesized RNAs containing site-specific Remdesivir and Molnupiravir-derived nucleotides helped to elucidate the mechanisms how antiviral nucleotides interfere with SARS-CoV-2 replication.

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