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Nuclear Magnetic Resonance of Hyperpolarized Fluorine for Characterization of Protein-Ligand Interactions

Title
Nuclear Magnetic Resonance of Hyperpolarized Fluorine for Characterization of Protein-Ligand Interactions
Author
이영복
Keywords
HIGH-AFFINITY LIGANDS; NMR-SPECTROSCOPY; DRUG DISCOVERY; CONSTANTS; BINDING; TIMES
Issue Date
2012-09
Publisher
Amer Chemical SOC
Citation
Journal of the American Chemical Society, Oct 2012, 134(42), P.17448-17451
Abstract
Fluorine NMR spectroscopy is widely used for detection of protein-ligand interactions in drug discovery because of the simplicity of fluorine spectra combined with a relatively high likelihood for a drug molecule to include at least one fluorine atom. In general, an important limitation of NMR spectroscopy in drug discovery is its sensitivity, which results in the need for unphysiologically high protein concentrations and large ligand:protein ratios. An enhancement in the F-19 signal of several thousand fold by dynamic nuclear polarization allows for the detection of submicromolar concentrations of fluorinated small molecules. Techniques for exploiting this gain in signal to detect ligands in the strong-, intermediate-, and weak-binding regimes are presented. Similar to conventional NMR analysis, dissociation constants are determined. However, the ability to use a low ligand concentration permits the detection of ligands in slow exchange that are not easily amenable to drug screening by traditional NMR methods. The relative speed and additional information gained may make the hyperpolarization-based approach an interesting alternative for use in drug discovery.
URI
https://pubs.acs.org/doi/10.1021/ja308437h
ISSN
0002-7863
DOI
10.1021/ja308437h
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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