ESCAPE: Identifying how specific molecules bind to targets in cells using precise gene editing

ESCAPE identifies multiple covalent ligand-protein interactions that impair cancer cell growth.

• Chemical proteomics has mapped covalent ligands targeting cysteine residues across hundreds of human proteins.
• The ESCAPE platform allows for functional analysis of these covalent ligand interactions at specific sites within cells.
• Cysteine-to-serine substitutions are created to prevent covalent ligand-protein interactions, enabling assessment of their effects.
• This method quantifies the impact of ligand interactions on cellular behavior using resistance scores based on allele frequency.
• ESCAPE revealed that certain covalent ligands, such as azetidine butynamides, disrupt essential cellular processes in cancer cells.

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