Abstract
Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (<300–350 Da) and lower initial potency but higher ligand efficiency when compared to those from high-throughput screening. NMR spectroscopy has been widely used for FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.
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Acknowledgements
We would like to thank Yan Hou and Mark McCoy for developing the 1D proton NMR-based functional assay and Hugh Eaton and Corey Strickland for valuable discussions.
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Kim, HY., Wyss, D.F. (2015). NMR Screening in Fragment-Based Drug Design: A Practical Guide. In: Hempel, J., Williams, C., Hong, C. (eds) Chemical Biology. Methods in Molecular Biology, vol 1263. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2269-7_16
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DOI: https://doi.org/10.1007/978-1-4939-2269-7_16
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