Fragment-based drug discovery using NMR spectroscopy
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Nuclear magnetic resonance (NMR) spectroscopy has evolved into a powerful tool for fragment-based drug discovery over the last two decades. While NMR has been traditionally used to elucidate the three-dimensional structures and dynamics of biomacromolecules and their interactions, it can also be a very valuable tool for the reliable identification of small molecules that bind to proteins and for hit-to-lead optimization. Here, we describe the use of NMR spectroscopy as a method for fragment-based drug discovery and how to most effectively utilize this approach for discovering novel therapeutics based on our experience.
KeywordsNMR spectroscopy Fragment-based drug discovery Fragment-based screening Hit identification Fragment libraries
This research was supported in part by grants from the National Institutes of Health (NIH Director’s Pioneer Award 5DP1OD006933/8DP1CA174419 to S.W.F. and ARRA stimulus grant 5RC2CA148375 to L.J. Marnett). M.J.H. was supported by a postdoctoral fellowship from the Damon Runyon Cancer Research Foundation, and A.O.F. was supported by a postdoctoral fellowship from the German Academic Exchange Service (DAAD).
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