Cooperativity is an important parameter to understand the ternary complexes formed by protein degraders. We developed fluorine NMR competition binding experiments to determine cooperativity of PROTACs. We show applicability to estimate both positive and negative cooperativity, also with homo-dimerizers, and highlight key features and considerations for optimal assay development.
[NMR paper] Labeled Ligand Displacement: Extending NMR-Based Screening of Protein Targets.
Labeled Ligand Displacement: Extending NMR-Based Screening of Protein Targets.
Related Articles Labeled Ligand Displacement: Extending NMR-Based Screening of Protein Targets.
ACS Med Chem Lett. 2010 Sep 9;1(6):295-9
Authors: Swann SL, Song D, Sun C, Hajduk PJ, Petros AM
Abstract
NMR spectroscopy has enjoyed widespread success as a method for screening protein targets, especially in the area of fragment-based drug discovery. However, current methods for NMR-based screening all suffer certain limitations. Two-dimensional methods...
Estimating side-chain order in methyl-protonated, perdeuterated proteins via multiple-quantum relaxation violated coherence transfer NMR spectroscopy
Estimating side-chain order in methyl-protonated, perdeuterated proteins via multiple-quantum relaxation violated coherence transfer NMR spectroscopy
Abstract Relaxation violated coherence transfer NMR spectroscopy (Tugarinov et al. in J Am Chem Soc 129:1743â??1750, 2007) is an established experimental tool for quantitative estimation of the amplitudes of side-chain motions in methyl-protonated, highly deuterated proteins. Relaxation violated coherence transfer experiments monitor the build-up of methyl proton multiple-quantum coherences that can be created in magnetically equivalent...
[NMR paper] 31P NMR analysis of the DNA conformation induced by protein binding SRY/DNA complexes
31P NMR analysis of the DNA conformation induced by protein binding SRY/DNA complexes.
Related Articles 31P NMR analysis of the DNA conformation induced by protein binding SRY/DNA complexes.
Eur J Biochem. 2000 Feb;267(4):1223-9
Authors: Castagné C, Murphy EC, Gronenborn AM, Delepierre M
Complexes of the HMG box protein SRY with two duplexes of 8 and 14 base pairs have been studied by 31P NMR and complete assignment of all phosphorus signals of the bound DNA duplexes are presented. While for the free DNA, all 31P signals display limited...
Estimating the cooperativity of PROTAC-induced ternary complexes using (19)F NMR displacement assay
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