Development of stable isotope labeling methods for the characterization of functional dynamics in nucleic acids: Since the last seven years the research group Kreutz strongly focused on the synthesis of RNA phosphoramidite building blocks bearing site-specific 2H, 13C and 15N labels. The use of solid phase synthesis for NMR of RNA simplifies the interpretation of the NMR data as the number and positioning of the stable isotope labels can be freely be chosen. Further, the simple spin topologies (e.g. isolated 1H-13C spin pairs) facilitates the application of relaxation dispersion techniques that give insights into nucleic acid dynamics underlying their function in ligand binding or catalysis.

Influence of naturally occurring RNA modifications on the folding landscape: We also focus on how naturally occurring RNA modifications, such as simple methylations but also more complex side chains like the 5-oxyacetic acid modification influence the folding landscape of RNA. To this end, we develop synthetic strategies to obtain RNA building blocks not only comprising the desired modification but also stable isotope labels at selected positions. We these NMR active labels powerful NMR experiments, such as the relaxation dispersion experiment or the CEST experiment can be applied to RNAs containing the very modification. Thereby changes of the folding landscape induced by the modifier can be detected and also quantified.

Expanding the NMR toolbox for integrated structural biology of nucleic acids: In this research field we focus on the development of robust chemical tools that can be used in integrative structural biology approaches that target ribonucleoprotein (RNP) particles or RNA protein complexes with high molecular weight in general. In detail, we want to introduce the methyl TROSY technique in combination with deuteration to nucleic acid NMR spectroscopy to expand the addressable molecular weight of RNA protein complexes. We further want to simplify the application of PRE NMR in nucleic acid protein complexes.


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