Project Summary We propose to acquire a Bruker Avance Neo 2-channel 600 MHz NMR spectrometer with a BBFO CryoProbe and a SampleCase automation device, to be housed in the NMR Facility at the Barnett Institute of Northeastern University. This versatile configuration will transform the capabilities of the two aging and oversubscribed instruments in our NMR core, a 500 MHz Varian INOVA and a 400 MHz Varian Mercury Plus, to meet rapidly increasing demands for chemical and biological structural analysis. The cutting-edge CryoProbe and automation capabilities of the requested 600 MHz NMR will enable a range of innovative projects at the forefront of interdisciplinary biomedical research, leaving routine usage to the existing NMR instruments. The following NIH-funded projects of the major users of the instrument will benefit immediately from the new features of the instrument: Kinetic target-guided synthesis to modulate protein-protein interactions (R. Manetsch); Discovery of lead and tool compounds for probing and modulating protozoan parasite biology (M. Pollastri/L. Ferrins); de novo synthesis of biologically active natural products and carbohydrate motifs (G.A. O’Doherty); Targeting the endocannabinoid system in treating brain disorders (A. Makriyannis); Profiling secondary metabolites in cell extracts of uncultured bacteria (K. Lewis); Improving oligonucleotide biopharmaceuticals by steric protection (K. Zhang); Dynamics of processivity clamp proteins in bacterial DNA replication (P. Beuning); and Transport of biologically active molecules across tight epithelial barriers (W. Lencer, Harvard Medical School).