1.2 GHz NMR System

• Subject Area: Basic Research in Biology and Medicine
• Term: Funded in 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 232373812

The research goal of the BIN is devoted to the development of marker molecules for application in human neurodegenerative diseases, such as Alzheimer, Parkinson disease and ALS. This requires optimization of small molecules for biomolecular targets (BIN’s chemistry group) using structural biology tools and modelling (BIN’s computational biophysics group), adaption of these molecules to imaging modalities (microscopy’s BIN groups) and testing of those in animal models (NanoSims BINgroup) and in human patients (PET BIN group). The established and anticipated targets will include large intrinsically disordered and high-molecular weight proteins such as TDP43 (ALS), as well as membrane proteins. The structure and interaction of such proteins with small molecules will be investigated with the 1.2 GHz spectrometer in solution and molecular modelling (computational BIN group). Compared to the existing 900 MHz, which is the highest field presently available in Göttingen, resolution will increase by a factor of 3.16 in four-dimensional NMR experiments and sensitivity will increase by a factor of (1.2/0.9)1,5 = 1.53 if the line width does not change. This is the case for the targets that are in the focus of BIN, namely, intrinsically disordered proteins as well as high-molecular weight complexes and membrane proteins where methyl groups’ line widths are least affected by molecular weight. In addition, paramagnetically induced dipolar couplings and chemical shift variance important for relaxation dispersion measurements scale with (1.2/0.9)2. = 1.78. Based on experienceswith previous steps in magnetic field, we expect that the 1.2 GHz will allow the BIN/UMG to tackle applications that are of interest according to the BIN Research programme and that are currently outside of its grasp.

• DFG Programme: Major Research Instrumentation
• Instrumentation Group: 1740 Hochauflösende NMR-Spektrometer
• Applicant Institution: Georg-August-Universität Göttingen; Universitätsmedizin Göttingen
• Leader: Professor Dr. Markus Zweckstetter