NMR Reporter Screening for the Detection of High-Affinity Ligands

Binding is good, displacing is better. By adding a weakly binding reporter ligand to a mixture of protein and test compounds, NMR screening can identify strongly binding ligands by observing the displacement of the reporter ligand. For example, NMR screening identified, as a reporter ligand, a small...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2002-09, Vol.41 (18), p.3420-3423
Main Authors: Jahnke, Wolfgang, Floersheim, Philipp, Ostermeier, Christian, Zhang, Xiaolu, Hemmig, Rene, Hurth, Konstanze, Uzunov, Doncho P.
Format: Article
Language:English
Subjects:
3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
3-Hydroxysteroid Dehydrogenases - chemistry
Benzofurans - chemistry
Drug Design
Enzyme Inhibitors - chemistry
high-throughput screening
Humans
inhibitors
Ligands
Magnetic Resonance Spectroscopy
Models, Molecular
NMR spectroscopy
Proteins - chemistry
structure-activity relationships
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Summary:Binding is good, displacing is better. By adding a weakly binding reporter ligand to a mixture of protein and test compounds, NMR screening can identify strongly binding ligands by observing the displacement of the reporter ligand. For example, NMR screening identified, as a reporter ligand, a small fragment, 2‐acetylbenzofuran (1, gray skeleton), which binds to the active site of 3α‐HSD. A molecular model of the complex between 3α‐HSD and 1 is shown.
ISSN:1433-7851
1521-3773
DOI:10.1002/1521-3773(20020916)41:18<3420::AID-ANIE3420>3.0.CO;2-E