Tracking the mechanism of covalent molecular glue stabilization using native mass spectrometry
Carlo J. A. Verhoef, Danielle F. Kay, L.v. Dijck, Richard G. Doveston, Luc Brunsveld, Aneika C. Leney, Peter J. Cossar
Abstract
non-covalent binding events that govern molecular glue activity. Aldehyde-based molecular glue activity is initially regulated by cooperative non-covalent binding, followed by slow covalent ligation, further enhancing stabilization. This study provides a framework to investigate the mechanisms of covalent small molecule ligation and informs (covalent) molecular glue development.
Topics & Concepts
Covalent bondChemistryMass spectrometrySmall moleculeMolecular massMoleculeCombinatorial chemistryMolecular bindingBiochemistryChromatographyOrganic chemistryEnzymeAdvanced Proteomics Techniques and ApplicationsUbiquitin and proteasome pathwaysProtein Structure and Dynamics