Synthesis and biophysics of modified nucleotides

 

Keywords

Nucleotides and oligonucleotides, mRNA, 5’ cap, 7-methylguanosine
chemical modifcations, chemical synthesis, molecular biophysics,
enzyme inhibitors, molecular probes, protein-nucleic acid interactions, molecular mechanisms,
therapeutic mRNA

 

Research topics

At the Division of Biophysics, we conduct interdisciplinary research at the intersection of organic chemistry, molecular biology, and physics, focusing on the design and synthesis of chemically modified nucleosides, nucleotides, and oligonucleotides. These molecules serve as sophisticated molecular tools, enabling us to explore fundamental biological processes and develop cutting-edge therapeutic technologies.

From Synthesis to Molecular Mechanisms

Our research covers the full spectrum: from precision chemical synthesis to detailed biophysical characterization. We develop, among others:

• Fluorescent and ¹⁹F-labeled molecular probes, which allow for intracellular visualization and tracking of metabolic pathways.
• Inhibitors of nucleic acid-metabolizing enzymes, used to regulate and study key biological pathways.
• Conjugates with macromolecules and nanomaterials, designed for targeted nucleotide delivery and the identification of nucleotide-binding proteins.

Biophysics of mRNA and therapeutic potential

A core focus of our research is the structure of the 5' end of mRNA, known as the cap. We design synthetic cap analogs that modulate mRNA stability and translational activity. By employing biophysical methods, we investigate the molecular mechanisms of nucleic acid-protein interactions, allowing us to understand the thermodynamics and kinetics of these processes at the atomic level. Some of our analogs significantly enhance translation efficiency, offering substantial potential for the development of novel mRNA-based vaccines and gene therapies: https://pubs.acs.org/doi/10.1021/acs.accounts.3c00442 .
By combining a physicist’s analytical approach with chemical precision, we aim to uncover the molecular rules that will form the foundation of future personalized medicine.