Furan warheads for covalent trapping of weak protein–protein interactions: cross-linking of thymosin β4 to actin.
- Resource Type
- Article
- Authors
- Miret-Casals, Laia; Vannecke, Willem; Hoogewijs, Kurt; Arauz-Garofalo, Gianluca; Gay, Marina; Díaz-Lobo, Mireia; Vilaseca, Marta; Ampe, Christophe; Van Troys, Marleen; Madder, Annemieke
- Source
- Chemical Communications. 6/21/2021, Vol. 57 Issue 49, p6054-6057. 4p.
- Subject
- *THYMOSIN
*PROTEIN-protein interactions
*WARHEADS
*DRUG design
*LYSINE
- Language
- ISSN
- 1359-7345
We describe furan as a triggerable 'warhead' for site-specific cross-linking using the actin and thymosin β4 (Tβ4)-complex as model of a weak and dynamic protein–protein interaction (PPI) with known 3D structure and with application potential in disease contexts. The identified cross-linked residues demonstrate that lysine is a target for the furan warhead. The presented in vitro validation of covalently acting 'furan-armed' Tβ4-variants provides initial proof to further exploit furan-technology for covalent drug design targeting lysines. [ABSTRACT FROM AUTHOR]