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

Autor:	Béatrice Brion, Marc Le Borgne, Roderick E. Hubbard, Claire Raingeval, Isabelle Krimm, Olivier Cala
Přispěvatelé:	Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre National de la Recherche Scientifique (CNRS), Molécules bioactives et chimie médicinale (B2MC), Université de Lyon-Université de Lyon
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	solvent-exposed Magnetic Resonance Spectroscopy Stereochemistry Fragment-based lead discovery [CHIM.THER]Chemical Sciences/Medicinal Chemistry binding mode 01 natural sciences Glycogen phosphorylase [CHIM.ANAL]Chemical Sciences/Analytical chemistry saturation transfer difference Drug Discovery medicine Pharmacology Binding Sites 010405 organic chemistry Chemistry Ligand WaterLOGSY lcsh:RM1-950 A protein fragment-based lead discovery Proteins General Medicine Human serum albumin 0104 chemical sciences 010404 medicinal & biomolecular chemistry Epitope mapping lcsh:Therapeutics. Pharmacology Saturation transfer medicine.drug Research Paper
Zdroj:	Journal of Enzyme Inhibition and Medicinal Chemistry Journal of Enzyme Inhibition and Medicinal Chemistry, Informa Healthcare, 2019, 34 (1), pp.1218-1225. ⟨10.1080/14756366.2019.1636235⟩ Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 34, Iss 1, Pp 1218-1225 (2019)
ISSN:	1475-6374 1475-6366
Popis:	International audience; 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-x L , 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. ARTICLE HISTORY
Databáze:	OpenAIRE
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