We propose to upgrade an existing 600 MHz Bruker AVANCE liquid-state nuclear magnetic resonance spectrometer to perform NMR on biological solids. The current machine (1-year old) and the additionally requested equipment will become part of the University's Analytical Chemistry Instrumentation Facility (ACIF). Solid-state NMR has become an essential method of characterization for a wide range of medicinal systems in chemistry, biochemistry, materials science and biophysics. Its large impact within the University is witnessed by the diversity of projects put forth in this proposal. In particular, Michael Dunn and Len Mueller will study covalent intermediates bound to the ?-site of tryptophan synthase, Michael Pirrung will characterize solid-phase synthetic oral insulin mimics, Katie DeFea and Len Mueller will determine the solid-state structure of PAR-2 agonists, and Chris Reed will investigate reactive cations in inorganic and organic chemistry. These problems all share a common need for solid-state characterization. Although well equipped for liquid-state NMR, there are currently no University-wide facilities capable of solid-state NMR at UCR. As such, solid-state NMR equipment will fill a noticeable void in the types of NMR characterization that can be performed at UC Riverside. ? ? Relevance: The relationship between structure and biological activity drives the development of therapeutic agents. Here we propose to add a significant molecular imaging capability through solid-state magnetic resonance. The goal is to determine the molecular level details that govern the interaction between drug and target molecules and build our chemical intuition for designing novel, next-generation treatments. ? ? ?
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