High field NMR spectrometer for chemical biology research

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Most pharmaceuticals are small organic compounds that exert their influence by specifically interacting with a biological macromolecule such as a protein or nucleic acid and altering its function. The diversity of prospective therapeutic agents is enormous; the number small molecules that can exist in theory vastly exceeds the number that can ever be synthesized and tested. Thus our ability to control living systems chemically is limited primarily by the difficulty of uncovering appropriate molecules within the immense universe of possibilities. The field of Chemical Biology seeks to meet this challenge by studying the rules that govern macromolecule/drug interactions and how these interactions lead ultimately to a physiological effect. Two critical steps in this process are the synthesis of novel compounds and detailed characterization of their interactions with biological targets. In order for these steps to be successful, researchers must be able to elucidate the structures of the molecules in question with atomic resolution.Nuclear Magnetic Resonance (NMR) spectroscopy is an extremely powerful technique for determining the three-dimensional structures of organic compounds, biological macromolecules, and their complexes. We are requesting NMR equipment that will increase the availability and versatility of this vital tool in our research. The new infrastructure will be used to develop new synthetic routes to biologically important classes of compounds, improve chemically-modified oligonucleotides with potential applications against cancer, inflammatory, and infectious diseases, refine inhibitors of a bacterial drug-resistance enzyme, generate natural products and natural product hybrids, and study the fundamental thermodynamic principles underlying protein/drug interactions.