Ligand-Protein Affinity Studies Using Long-Lived States of Fluorine-19 Nuclei

The lifetimes T-LLS of long-lived states or T-LLC of long-lived coherences can be used for the accurate determination of dissociation constants of weak protein ligand complexes. The remarkable contrast between signals derived from LLS or LLC in free and bound ligands can be exploited to search for weak binders with large dissociation constants K-D > 1 mM that are important for fragment-based drug discovery but may escape detection by other screening techniques. Alternatively, the high sensitivity of the proposed method can be exploited to work with large ligand-to-protein ratios, with an evident advantage of reduced consumption of precious proteins. The detection of F-19-F-19 long-lived states in suitably designed fluorinated spy molecules allows one to perform competition binding experiments with high sensitivity while avoiding signal overlap that tends to hamper the interpretation of proton spectra of mixtures.


Published in:
Journal Of Medicinal Chemistry, 59, 5, 1960-1966
Year:
2016
Publisher:
Washington, American Chemical Society
ISSN:
0022-2623
Laboratories:




 Record created 2016-07-19, last modified 2018-09-13


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