Labeled Ligand Displacement: Extending NMR-Based Screening of Protein TargetsClick to copy article linkArticle link copied!
Abstract

NMR spectroscopy has enjoyed widespread success as a method for screening protein targets, especially in the area of fragment-based drug discovery. However, current methods for NMR-based screening all suffer certain limitations. Two-dimensional methods like “SAR by NMR” require isotopically labeled protein and are limited to proteins less than about 50 kDa. For one-dimensional, ligand-based methods, results can be confounded by nonspecific compound binding, resonance overlap, or the need for a special NMR probe. We present here a ligand-based method that relies on the exchange broadening observed for a 13C-labeled molecule upon binding to a protein target (labeled ligand displacement). This method can be used to screen both individual compounds and mixtures and is free of the artifacts inherent in other ligand-based methods.
Cited By
Smart citations by scite.ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by ACS Publications if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles.
This article is cited by 12 publications.
- Ivanhoe K. H. Leung, Marina Demetriades, Adam P. Hardy, Clarisse Lejeune, Tristan J. Smart, Andrea Szöllössi, Akane Kawamura, Christopher J. Schofield, and Timothy D. W. Claridge . Reporter Ligand NMR Screening Method for 2-Oxoglutarate Oxygenase Inhibitors. Journal of Medicinal Chemistry 2013, 56
(2)
, 547-555. https://doi.org/10.1021/jm301583m
- Yanhu Wei, Paul J. Wesson, Igor Kourkine, and Bartosz A. Grzybowski. Measurement of Protein−Ligand Binding Constants from Reaction-Diffusion Concentration Profiles. Analytical Chemistry 2010, 82
(21)
, 8780-8784. https://doi.org/10.1021/ac102055a
- Theresa Höfurthner, Borja Mateos, Robert Konrat. On‐Cell NMR Contributions to Membrane Receptor Binding Characterization. ChemPlusChem 2021, 86
(6)
, 938-945. https://doi.org/10.1002/cplu.202100134
- Timothy D.W. Claridge. Protein–Ligand Screening by NMR. 2016, 421-455. https://doi.org/10.1016/B978-0-08-099986-9.00011-7
- Patrick Garidel, Alfred Blume, Michael Wagner. Prediction of colloidal stability of high concentration protein formulations. Pharmaceutical Development and Technology 2015, 20
(3)
, 367-374. https://doi.org/10.3109/10837450.2013.871032
- Carlos Gómez-Castro, Itzia Padilla-Martínez, Efrén García-Báez, José Castrejón-Flores, Ana Peraza-Campos, Francisco Martínez-Martínez. Solid State Structure and Solution Thermodynamics of Three-Centered Hydrogen Bonds (O∙∙∙H∙∙∙O) Using N-(2-Benzoyl-phenyl) Oxalyl Derivatives as Model Compounds. Molecules 2014, 19
(9)
, 14446-14460. https://doi.org/10.3390/molecules190914446
- Adam J. Plaunt, Kasey J. Clear, Bradley D. Smith. 19
F NMR indicator displacement assay using a synthetic receptor with appended paramagnetic relaxation agent. Chem. Commun. 2014, 50
(72)
, 10499-10501. https://doi.org/10.1039/C4CC04159C
- Bernd Beck, Michael Bieler, Peter Haebel, Andreas Teckentrup, Alexander Weber, Nils Weskamp. APPLICATIONS OF CHEMINFORMATICS IN PHARMACEUTICAL RESEARCH. 2013, 291-320. https://doi.org/10.1002/9781118742785.ch13
- Susan M. Boyd, Andrew P. Turnbull, Björn Walse. Fragment library design considerations. WIREs Computational Molecular Science 2012, 2
(6)
, 868-885. https://doi.org/10.1002/wcms.1098
- Laurel O. Sillerud, Richard S. Larson. Advances in Nuclear Magnetic Resonance for Drug Discovery. 2012, 195-266. https://doi.org/10.1007/978-1-61779-965-5_10
- Renaldo Mendoza, Andrew M. Petros, Yaya Liu, Rama Thimmapaya, Carol S. Surowy, Walter F. Leise, Ana Pereda-Lopez, Sanjay C. Panchal, Chaohong Sun. Cracking the molecular weight barrier: Fragment screening of an aminotransferase using an NMR-based functional assay. Bioorganic & Medicinal Chemistry Letters 2011, 21
(18)
, 5248-5250. https://doi.org/10.1016/j.bmcl.2011.07.039
- Christopher A. Lepre. Practical Aspects of NMR-Based Fragment Screening. 2011, 219-239. https://doi.org/10.1016/B978-0-12-381274-2.00009-1
Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.
Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.
The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.