Quantifying Protein Homodimer Affinities and the Effect of Molecular Glues and Interface Residues Using Native Mass Spectrometry
s in the high micromolar range, which allowed us to monitor the gradual decrease in homodimer affinity via mutation of crucial dimer interface contacts. Overall, qLILBID-MS is a sensitive, robust, fast, scalable, and cost-effective alternative to quantify protein/protein interactions, that can accelerate contemporary drug discovery workflows, e.g. the efficient screening for proximity inducing molecules like proteolysis targeting chimera (PROTACs) and molecular glues.
Authors
- Nina Morgner (ORCID: https://orcid.org/0000-0002-1872-490X)
- Ute A. Hellmich (ORCID: https://orcid.org/0000-0001-7162-285X)
- Jonathan Schulte (ORCID: https://orcid.org/0000-0003-0675-7357)
- Eric Schwegler
Institutions
- Goethe University Frankfurt (DE)
- Goethe-Institute United Kingdom (GB)
- Schiller International University (FR)
- Institute of Macromolecular Chemistry (UA)
- FuelCell Energy (United States) (US)
- Resonance Research (United States) (US)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1021/jacs.5c18602
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft