Fast NMR Methods for Measuring in the Direct and/or Competition Mode the Dissociation Constants of Chemical Fragments Interacting with a Receptor

ChemMedChem
Claudio DalvitAlexey Rak

Abstract

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.

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Citations

Apr 30, 2020·Journal of Biomolecular NMR·Claudio DalvitAnna Vulpetti
Jun 28, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·J Daniel MartínezF Javier Cañada
Jun 20, 2020·Journal of Biomolecular NMR·Simon H RüdisserAlvar D Gossert

Related Concepts

Ligands
In Vivo NMR Spectroscopy
HSP90 Heat-Shock Proteins
Drug Prospecting
Chemistry, Pharmaceutical
Ligands
Chemicals
Binding Protein
HSP90 Heat-Shock Proteins
Receptor

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