Structure-based drug development suffers from high attrition rates due to the poor activity of lead compounds in cellular and animal models caused by low cell penetrance, off-target binding or changes in the conformation of the target protein in the cellular environment. The latter two effects cause a change in the apparent binding affinity of the compound, which is indirectly assessed by cellular activity assays. To date, direct measurement of the intracellular binding affinity remains a...
[NMR paper] Intracellular binding/unbinding kinetics of approved drugs to carbonic anhydrase II observed by in-cell NMR.
Intracellular binding/unbinding kinetics of approved drugs to carbonic anhydrase II observed by in-cell NMR.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-pubmed-acspubs.jpg Related Articles Intracellular binding/unbinding kinetics of approved drugs to carbonic anhydrase II observed by in-cell NMR.
ACS Chem Biol. 2020 Sep 21;:
Authors: Luchinat E, Barbieri L, Cremonini M, Nocentini A, Supuran CT, Banci L
Abstract
Candidate drugs rationally designed in vitro often fail due to low...
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09-24-2020 07:17 PM
[NMR paper] Determination of protein-ligand binding modes using fast multi-dimensional NMR with hyperpolarization.
Determination of protein-ligand binding modes using fast multi-dimensional NMR with hyperpolarization.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.rsc-cdn.org-oxygen-assets-logo-rsc-logo-btn-small.gif http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles Determination of protein-ligand binding modes using fast multi-dimensional NMR with hyperpolarization.
Chem Sci. 2020 Jun 21;11(23):5935-5943
Authors: Wang Y, Kim J, Hilty C...
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09-13-2020 09:18 AM
[NMR paper] Real-time quantitative in-cell NMR: ligand binding and protein oxidation monitored in human cells using multivariate curve resolution.
Real-time quantitative in-cell NMR: ligand binding and protein oxidation monitored in human cells using multivariate curve resolution.
Related Articles Real-time quantitative in-cell NMR: ligand binding and protein oxidation monitored in human cells using multivariate curve resolution.
Anal Chem. 2020 Jun 18;:
Authors: Luchinat E, Barbieri L, Campbell TF, Banci L
Abstract
In-cell NMR can investigate at atomic resolution protein conformational changes, such as those induced by drug binding or chemical modifications, directly in...
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06-20-2020 03:40 PM
[NMR paper] Solution NMR Studies of the Ligand-Binding Domain of an Orphan Nuclear Receptor Reveals a Dynamic Helix in the Ligand-Binding Pocket.
Solution NMR Studies of the Ligand-Binding Domain of an Orphan Nuclear Receptor Reveals a Dynamic Helix in the Ligand-Binding Pocket.
Solution NMR Studies of the Ligand-Binding Domain of an Orphan Nuclear Receptor Reveals a Dynamic Helix in the Ligand-Binding Pocket.
Biochemistry. 2018 Mar 16;:
Authors: Daffern N, Chen Z, Zhang Y, Pick L, Radhakrishnan I
Abstract
The ligand-binding domains (LBD) of the NR5A subfamily of nuclear receptors activate transcription via ligand-dependent and ligand-independent mechanisms. The...
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03-17-2018 12:12 PM
[NMR paper] Fast NMR-Based Determination of the 3D Structure of the Binding Site of Protein-Ligand Complexes with Weak Affinity Binders.
Fast NMR-Based Determination of the 3D Structure of the Binding Site of Protein-Ligand Complexes with Weak Affinity Binders.
Fast NMR-Based Determination of the 3D Structure of the Binding Site of Protein-Ligand Complexes with Weak Affinity Binders.
Angew Chem Int Ed Engl. 2017 Apr 07;:
Authors: Wälti MA, Riek R, Orts J
Abstract
In early drug discovery approaches, screening hits are often weak affinity binders that are difficult to characterize in structural detail, particularly towards obtaining the 3D structure of...
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04-08-2017 10:57 AM
Determination of ligand binding modes in weak proteinâ??ligand complexes using sparse NMR data
Determination of ligand binding modes in weak proteinâ??ligand complexes using sparse NMR data
Abstract
We describe a general approach to determine the binding pose of small molecules in weakly bound proteinâ??ligand complexes by deriving distance constraints between the ligand and methyl groups from all methyl-containing residues of the protein. We demonstrate that using a single sample, which can be prepared without the use of expensive precursors, it is possible to generate high-resolution data rapidly and obtain the resonance assignments of...
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11-19-2016 08:35 PM
Binding site identification and structure determination of protein-ligand complexes by NMR a semiautomated approach.
Binding site identification and structure determination of protein-ligand complexes by NMR a semiautomated approach.
Binding site identification and structure determination of protein-ligand complexes by NMR a semiautomated approach.
Methods Enzymol. 2011;493:241-75
Authors: Ziarek JJ, Peterson FC, Lytle BL, Volkman BF
Over the last 15years, the role of NMR spectroscopy in the lead identification and optimization stages of pharmaceutical drug discovery has steadily increased. NMR occupies a unique niche in the biophysical analysis of drug-like...
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03-05-2011 01:02 PM
[NMR paper] Determination of protein-ligand binding affinity by NMR: observations from serum albu
Determination of protein-ligand binding affinity by NMR: observations from serum albumin model systems.
Related Articles Determination of protein-ligand binding affinity by NMR: observations from serum albumin model systems.
Magn Reson Chem. 2005 Jun;43(6):463-70
Authors: Fielding L, Rutherford S, Fletcher D
The usefulness of bovine serum albumin (BSA) as a model protein for testing NMR methods for the study of protein-ligand interactions is discussed. Isothermal titration calorimetry established the binding affinity and stoichiometry of the...
Determination of intracellular protein-ligand binding affinity by competition binding in-cell NMR
Linear Mode
