19F multiple-quantum coherence NMR spectroscopy for probing protein–ligand interactions. Issue 71 (5th December 2018)

• Record Type: Journal Article
• Authors: Zawadzka-Kazimierczuk, Anna; Somlyay, Mate; Kaehlig, Hanspeter; Iakobson, George; Beier, Petr; Konrat, Robert
• Is Part Of: RSC advances. Volume 8:Issue 71(2018)
• Page Start: 40687
• Page End: 40692
• Publication Date: 2018-12-05
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c8ra09296f
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : An NMR experiment is presented that allows identification of weak binders typically found in early stages of drug discovery programs. Abstract : A new 19 F NMR method is presented which can be used to detect weak protein binding of small molecules with up to mM affinity. The method capitalizes on the synthetic availability of unique SF5 containing compounds and the generation of five-quantum coherences (5QC). Given the high sensitivity of 5QC relaxation to exchange events ( i.e. reversible protein binding) fragments which bind to the target with weak affinity can be identified. The utility of the method in early stage drug discovery programs is demonstrated with applications to two model proteins, the neurotoxic NGAL and the prominent tumor target β-catenin.