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

Claudio DalvitAlexey Rak


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.


Nov 1, 1992·Journal of Biomolecular NMR·Martial PiottoV Sklenár
Oct 1, 1987·Molecular and Biochemical Parasitology·M P LearmonthW A Gibbons
Jan 1, 1997·Journal of Magnetic Resonance·T L HwangM Garwood
Feb 5, 2002·Journal of Biomolecular NMR·Claudio DalvitBrian J Stockman
Jun 27, 2002·Journal of the American Chemical Society·Claudio DalvitMario Varasi
Feb 13, 2003·Current Topics in Medicinal Chemistry·Lee Fielding
Feb 14, 2003·Chemistry : a European Journal·Richard E HeathDavid K Smith
Jun 19, 2003·Journal of the American Chemical Society·Claudio DalvitBrian J Stockman
May 12, 2004·Magnetic Resonance in Chemistry : MRC·Yu-Sen WangDaniel F Wyss
Aug 25, 2004·Analytical Biochemistry·Zaneta Nikolovska-ColeskaShaomeng Wang
Apr 9, 2005·Magnetic Resonance in Chemistry : MRC·Lee FieldingDan Fletcher
Jun 22, 2005·Journal of Pharmaceutical and Biomedical Analysis·Guoyun BaiMaili Liu
Oct 4, 2008·Journal of Combinatorial Chemistry·Matthew D ShortridgeRobert Powers
Aug 26, 2009·Journal of the American Chemical Society·Anna VulpettiClaudio Dalvit
Jul 20, 1943·The Journal of General Physiology·O H StrausTechnical Assistance of Frank L. Plachte
Aug 20, 2010·Journal of Medicinal Chemistry·Christopher W MurrayAlison J-A Woolford
Mar 10, 2011·Magnetic Resonance in Chemistry : MRC·Claudio DalvitMartial Piotto
Sep 29, 2011·European Biophysics Journal : EBJ·Jesus Angulo, Pedro M Nieto
Dec 7, 2011·Chemical Communications : Chem Comm·Juan A AguilarGareth A Morris
Dec 15, 2011·Journal of Medicinal Chemistry·John B JordanWenge Zhong
Apr 7, 2012·Drug Discovery Today·Anna Vulpetti, Claudio Dalvit
Jun 13, 2012·Journal of the American Chemical Society·Nicola SalviGeoffrey Bodenhausen
Aug 22, 2012·Angewandte Chemie·Thomas LombèsCarine Tisné
Dec 14, 2012·Journal of Medicinal Chemistry·Ivanhoe K H LeungTimothy D W Claridge
Jul 2, 2014·Bioorganic & Medicinal Chemistry·Elena CasaleFrancesco Casuscelli
Sep 10, 2014·ChemMedChem·Roberto BurattoGeoffrey Bodenhausen
Feb 24, 2015·Angewandte Chemie·Yaewon Kim, Christian Hilty
May 9, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Federico Riccardi SirtoriG Fogliatto
Dec 8, 2015·Journal of Biomolecular Screening·Pawel LinkeAlexey Rak
Jan 23, 2016·Journal of Medicinal Chemistry·Roberto BurattoGeoffrey Bodenhausen
Jul 16, 2016·Nature Reviews. Drug Discovery·Daniel A ErlansonHarren Jhoti
Aug 16, 2016·Nature Reviews. Drug Discovery·Jean-Paul RenaudHerbert Nar
Sep 24, 2016·Magnetic Resonance in Chemistry : MRC·Luis Pablo Calle, Juan Félix Espinosa
Nov 28, 2016·Progress in Nuclear Magnetic Resonance Spectroscopy·Alvar D Gossert, Wolfgang Jahnke
Sep 15, 2017·Journal of Medicinal Chemistry·Leonhard GeistRobert Konrat
Jun 14, 1999·Angewandte Chemie·Moriz Mayer, Bernd Meyer
Aug 26, 2018·Journal of Magnetic Resonance·Yaewon KimChristian Hilty
Oct 9, 2018·Journal of Medicinal Chemistry·Claudio Dalvit, Anna Vulpetti
Jan 15, 2019·Methods in Enzymology·Renjie Huang, Ivanhoe K H Leung
Jan 16, 2019·Chemical Communications : Chem Comm·Guilherme Vieira de Castro, Alessio Ciulli


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

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

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