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Fragment-based drug discovery using NMR spectroscopy

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Abstract

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.

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Acknowledgments

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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  1. Andreas O. Frank

    Present address: Novartis Institutes for BioMedical Research (NIBR), Global Discovery Chemistry, Emeryville, CA, USA

Authors and Affiliations

  1. Department of Biochemistry, Vanderbilt University School of Medicine, 2215 Garland Ave, 607 Light Hall, Nashville, TN, 37232-0146, USA

    Mary J. Harner, Andreas O. Frank & Stephen W. Fesik

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  1. Mary J. Harner
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  2. Andreas O. Frank
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Correspondence to Stephen W. Fesik.

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Mary J. Harner and Andreas O. Frank contributed equally to this work.

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Harner, M.J., Frank, A.O. & Fesik, S.W. Fragment-based drug discovery using NMR spectroscopy. J Biomol NMR 56, 65–75 (2013). https://doi.org/10.1007/s10858-013-9740-z

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