New preprint: Estimating the cooperativity of PROTAC-induced ternary complexes using 19F NMR displacement assay

  • ToC graphics
  • Figure 1. General setup of the competitive 19F NMR assay to determine cooperativity.
  • Scheme 1. Structures of 19F NMR VHL spy molecule 19 and PROTACs MZ1, MZP-54, MZP-55 and MZP-61.
  • Figure 2. 19F NMR displacement curves in the presence of BET-targeting PROTACs.
  • Scheme 3. Structures of 19F NMR VHL spy molecules 7 and 18.
  • Figure 3. F19 transverse relaxation times of spy molecules.
  • Figure 4. Evaluation of a weaker VHL-targeting PROTAC.
  • Figure 5. Evaluation of VHL homo-PROTACs

Great work by Gugi.

Read the pre-print article here

Authors: Guilherme Castro, Alessio Ciulli*

Title: Estimating the cooperativity of PROTAC-induced ternary complexes using 19F NMR displacement assay

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.