The authors report the development of dual covalent proximity inducing molecules capable of selectively cross-linking two non-interacting proteins. Through the selective proximity-based activation of two SuFEx electrophiles, a functional ternary complex of interest can be trapped kinetically which mimics the thermodynamic stabilization associated with molecular glues. This work further demonstrates that “covalent glue mimics” can efficiently and selectively crosslink tumor immunotherapeutically relevant proteins to stabilize and promote cell-cell interactions enacting tumor cell clearance.
- Eden Kapcan
- Karolina Krygier
- Anthony F. Rullo
