title: Ligand-Protein Affinity Studies Using Long-Lived States of Fluorine-19 Nuclei.
abstract: The lifetimes TLLS of long-lived states or TLLC 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 KD > 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 (19)F-(19)F 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.
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne , 1015 Lausanne, Switzerland.
authors.forename: Roberto
authors.initials: R
authors.lastname: Buratto
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne , 1015 Lausanne, Switzerland.
authors.forename: Daniele
authors.initials: D
authors.lastname: Mammoli
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne , 1015 Lausanne, Switzerland.|Département de Chimie, Ecole Normale Supérieure-PSL Research University , 24 Rue Lhomond, 75231 Paris Cedex 05, France.|Sorbonne Université, UPMC Univ Paris 06 , 4 place Jussieu, 75005 Paris, France.|CNRS, UMR 7203 LBM , 75005 Paris, France.
authors.forename: Estel
authors.initials: E
authors.lastname: Canet
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne , 1015 Lausanne, Switzerland.|Département de Chimie, Ecole Normale Supérieure-PSL Research University , 24 Rue Lhomond, 75231 Paris Cedex 05, France.|Sorbonne Université, UPMC Univ Paris 06 , 4 place Jussieu, 75005 Paris, France.|CNRS, UMR 7203 LBM , 75005 Paris, France.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Bodenhausen
mesh_terms: D015195:Drug Design; D005461:Fluorine / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D014357:Trypsin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D005461:Fluorine; D014357:Trypsin