Estimating the cooperativity of PROTAC-induced ternary complexes using <sup>19</sup> F NMR displacement assay
Guilherme V. Castro, Alessio Ciulli
Abstract
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.
Topics & Concepts
CooperativityTernary operationTernary complexCooperative bindingChemistryDisplacement (psychology)CrystallographyComputational chemistryBinding siteBiochemistryComputer scienceEnzymeProgramming languagePsychotherapistPsychologyProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysPeptidase Inhibition and Analysis