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Fast NMR Methods for Measuring in the Direct and/or Competition Mode the Dissociation Constants of Chemical Fragments Interacting with a Receptor
Author(s) -
Dalvit Claudio,
Parent Annick,
Vallée Francois,
Mathieu Magali,
Rak Alexey
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900152
Subject(s) - chemistry , dissociation constant , drug discovery , affinities , ligand (biochemistry) , chemical shift , dissociation (chemistry) , computational chemistry , receptor , stereochemistry , biochemistry
Ligand‐based NMR screening represents a powerful method in fragment‐based drug discovery for the identification of chemical matter interacting with the receptor of interest. The large dynamic range of these methods allows the detection of weakly binding ligands. However, the methodology has not been extensively used for quantifying the strength of these interactions. This knowledge is important for ranking fragments according to their binding strength and for prioritizing structure‐based and medicinal chemistry activities. Rapid NMR methods for measuring the dissociation constant in direct and competition modes are presented here. The theory underpinning these methods are presented, along with their application to the measurement of the binding affinities of several ligands of the heat shock protein 90.