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

Claire Raingeval, Olivier Cala, Béatrice Brion, Marc Le Borgne, Roderick Eliot Hubbard, Isabelle Krimm*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1218-1225
Number of pages8
JournalJOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
Volume34
Issue number1
Early online date9 Jul 2019
DOIs
Publication statusE-pub ahead of print - 9 Jul 2019

Bibliographical note

© 2019 The Author(s).

Keywords

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

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