For initial hit identification in fragment-based drug design, NMR is one of the preferred methods, with the well-established ligand screening experiments T1?, waterLOGSY and STD. Here, we present a new, perfect echo-based experiment with superior binding sensitivity, the PEARLScreen. The sensitivity enhancement is based on longer relaxation delays as well as active exchange broadening, enabled by the perfect echo scheme. This allowed a reduction of the protein concentration by up to one order of...
[NMR paper] Determination of Ligand-Binding Affinity (Kd) Using Transverse Relaxation Rate (R2) in the Ligand-Observed 1H NMR Experiment and Applications to Fragment-Based Drug Discovery
Determination of Ligand-Binding Affinity (Kd) Using Transverse Relaxation Rate (R2) in the Ligand-Observed 1H NMR Experiment and Applications to Fragment-Based Drug Discovery
High hit rates from initial ligand-observed NMR screening can make it challenging to prioritize which hits to follow up, especially in cases where there are no available crystal structures of these hits bound to the target proteins or other strategies to provide affinity ranking. Here, we report a reproducible, accurate, and versatile quantitative ligand-observed NMR assay, which can determine K(d) values of fragments...
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07-20-2023 06:33 AM
[NMR paper] (19)F NMR viewed through two different lenses: ligand-observed and protein-observed (19)F NMR applications for fragment-based drug discovery
(19)F NMR viewed through two different lenses: ligand-observed and protein-observed (19)F NMR applications for fragment-based drug discovery
^(19)F NMR has emerged as a powerful tool in drug discovery, particularly in fragment-based screens. The favorable magnetic resonance properties of the fluorine-19 nucleus, the general absence of fluorine in biological settings, and its ready incorporation into both small molecules and biopolymers, has enabled multiple applications of ^(19)F NMR using labeled small molecules and proteins in biophysical, biochemical, and cellular experiments. This...
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10-27-2021 10:50 PM
[NMR paper] Protein-Observed Fluorine NMR is a Complementary Ligand Discovery Method to 1H CPMG Ligand-Observed NMR.
Protein-Observed Fluorine NMR is a Complementary Ligand Discovery Method to 1H CPMG Ligand-Observed NMR.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-pubmed-acspubs.jpg Related Articles Protein-Observed Fluorine NMR is a Complementary Ligand Discovery Method to 1H CPMG Ligand-Observed NMR.
ACS Chem Biol. 2016 Sep 14;
Authors: Urick AK, Calle Jiménez LP, Espinosa JF, Hu H, Pomerantz WC
Abstract
To evaluate its potential as a ligand discovery tool, we compare a newly developed...
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09-22-2016 06:31 AM
[NMR paper] Protein-observed (19)F-NMR for fragment screening, affinity quantification and druggability assessment.
Protein-observed (19)F-NMR for fragment screening, affinity quantification and druggability assessment.
Protein-observed (19)F-NMR for fragment screening, affinity quantification and druggability assessment.
Nat Protoc. 2016 Aug;11(8):1414-27
Authors: Gee CT, Arntson KE, Urick AK, Mishra NK, Hawk LM, Wisniewski AJ, Pomerantz WC
Abstract
NMR spectroscopy can be used to quantify the binding affinity between proteins and low-complexity molecules, termed 'fragments'; this versatile screening approach allows researchers to assess the...
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07-16-2016 04:54 AM
[NMR paper] Exploring Weak Ligand-Protein Interactions by Long-Lived NMR States : Improved Contrast in Fragment-Based Drug Screening.
Exploring Weak Ligand-Protein Interactions by Long-Lived NMR States : Improved Contrast in Fragment-Based Drug Screening.
Related Articles Exploring Weak Ligand-Protein Interactions by Long-Lived NMR States : Improved Contrast in Fragment-Based Drug Screening.
Angew Chem Int Ed Engl. 2014 Sep 4;
Authors: Buratto R, Mammoli D, Chiarparin E, Williams G, Bodenhausen G
Abstract
Ligands that have an affinity for protein targets can be screened very effectively by exploiting favorable properties of long-lived states (LLS) in NMR...
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09-10-2014 11:24 AM
Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
J Mol Graph Model. 2011 Sep 3;
Authors: Fukunishi Y, Mizukoshi Y, Takeuchi K, Shimada I, Takahashi H, Nakamura H
Abstract
We developed a new protein-ligand docking calculation method using experimental NMR data. Recently, we proposed a novel ligand epitope-mapping experiment, which utilizes the difference between the longitudinal relaxation rates of ligand protons with and...
Higher Contrast in 1H-Observed NMR Ligand Screening with the PEARLScreen Experiment
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