NMR console 500 MHz

• Subject Area: Basic Research in Biology and Medicine
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 581871163

The proposed NMR console will upgrade our existing 500 MHz NMR spectrometer for measurements in liquids. Using this spectrometer, the Biophysics research group investigates the structure and dynamics of biomacromolecules and their interactions with proteins, peptides, nucleic acids, and small-molecule drugs. From a structural biology perspective, we examine binding sites and induced conformational changes by interacting partners. For small proteins and peptides, as well as for organic drugs, the NMR resonances are assigned using this spectrometer through multidimensional experiments with the NMR-active nuclei in their natural abundance or after isotopic labeling. These structure-activity relationships are further explored through dynamic investigations, including diffusion and relaxation experiments. For a reliable investigation of local protein dynamics, relaxation experiments at different field strengths are essential. The 500 MHz spectrometer with 11.7 T expands the research group's capabilities beyond the existing 14.1 T and 18.8 T fields. In addition to fast protein dynamics on the nano- to picosecond timescale, we investigate exchange processes using R2 dispersion and R1roh measurements on globular and intrinsically unfolded proteins, exploring how these processes are influenced by the environment (molecular crowding) and interaction partners. Furthermore, we intensively study selectively isotopically labeled proteins, as the resolution at 11.7 T is perfectly adequate, and some relaxation properties are even advantageous for determining, for example, the flipping of aromatic rings or local pKA in protein active sites. Another application of the 500 MHz spectrometer is the structural analysis of organic drugs bound to their target proteins using transfer-NOE experiments. Here, in cooperation with the Pharmaceutical and Medical Institutes of our university, we are testing a large number of already patented active ingredients for cancer therapy. Despite sufficient resolution and sensitivity at 11.7 T, we encountered technical limitations when implementing modern pulse sequences on the older 500 MHz console (e.g., long-term stability in transfer NOE measurements with long mixing times or in R2 measurements for the exchange kinetics of protein side-group protons). For these sometimes very time-consuming measurements, we had to switch to the modern 600 MHz spectrometer, where the experiments could then be carried out successfully. We are further optimizing the sample conditions for NMR studies of plant, bacterial, and human proteins at 500 MHz before subjecting them to detailed structural and dynamical investigations on the 800 MHz spectrometer with a cryoprobe. The range of protein NMR methods will be expanded to include 19F measurements through the console upgrade.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: NMR-Konsole 500 MHz (Erneuerung)
• Instrumentation Group: 1740 Hochauflösende NMR-Spektrometer
• Applicant Institution: Martin-Luther-Universität Halle-Wittenberg
• Leader: Professor Dr. Jochen Balbach