Raingeval, Claire, Cala, Olivier, Brion, Béatrice et al. (3 more authors) (2019) 1D NMR WaterLOGSY as an efficient method for fragment-based lead discovery. JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. pp. 1218-1225. ISSN 1475-6366
Abstract
WaterLOGSY is a sensitive ligand-observed NMR experiment for detection of interaction between a ligand and a protein and is now well-established as a screening technique for fragment-based lead discovery. Here we develop and assess a protocol to derive ligand epitope mapping from WaterLOGSY data and demonstrate its general applicability in studies of fragment-sized ligands binding to six different proteins (glycogen phosphorylase, protein peroxiredoxin 5, Bcl-xL, Mcl-1, HSP90, and human serum albumin). We compare the WaterLOGSY results to those obtained from the more widely used saturation transfer difference experiments and to the 3D structures of the complexes when available. In addition, we evaluate the impact of ligand labile protons on the WaterLOGSY data. Our results demonstrate that the WaterLOGSY experiment can be used as an additional confirmation of the binding mode of a ligand to a protein.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Author(s). |
Keywords: | binding mode,fragment-based lead discovery,saturation transfer difference,solvent-exposed,WaterLOGSY |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 29 Aug 2019 08:20 |
Last Modified: | 08 Feb 2025 00:35 |
Published Version: | https://doi.org/10.1080/14756366.2019.1636235 |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.1080/14756366.2019.1636235 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:150182 |
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Description: 1D NMR WaterLOGSY as an efficient method for fragment based lead discovery
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