Figure 6.

CLASH enables on/off switching of POI activity by making use of two ligands with mutually exclusive binding to POI. Tethering results in intramolecular protein–ligand interaction that is disrupted by an effector biomolecule [streptavidin in (a) and (b)] or small molecule [tacrine in (c)] that competes with the ligand within the tethered array that initially binds POI. In (b), only the ground state in the absence of streptavidin is shown. POI is exemplified by nanoluciferase (a) and HCA (b,c).