Figure 4. Different strategies for finding compounds to target acquired cysteines.
A. The first strategy is based on modification of an available non-covalent binder to include a cysteine-reactive moiety that cross-links it to an acquired cysteine in or near the binding pocket of the non-covalent binder. B. The second strategy uses a screen with a library of thiophiles as its basis for drug discovery. Thiophiles may include disulfides and irreversible and reversible electrophiles like acrylates and cyano-acrylamides respectively conjugated to different R groups that can provide selectivity for the target.