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1D NMR WaterLOGSY as an efficient method for fragment-based lead discovery

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Publication details

JournalJOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
DateAccepted/In press - 18 Jun 2019
DateE-pub ahead of print (current) - 9 Jul 2019
Issue number1
Volume34
Number of pages8
Pages (from-to)1218-1225
Early online date9/07/19
Original languageEnglish

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.

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© 2019 The Author(s).

    Research areas

  • binding mode, fragment-based lead discovery, saturation transfer difference, solvent-exposed, WaterLOGSY

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