To identify the target of compounds that reactivate the silenced frataxin gene in Friedreich's ataxia, the research team synthesized an activity profiling probe. This molecule has a multiple components: the two rings that make up the active compound, a crosslinking agent (the arrow), a linker region, and a chemical group called an alkyne for attachment of a dye (green sphere), which is linked to another chemical group called an azide. The azide reacts with the alkyne through "click chemistry" to form a covalent bond. This then lights up the target of the compound. The active compound, a histone deacetylase inhibitor, changes the structure of nucleosomes bound to DNA (center). Blue and green structures are other proteins, such as other histone deacetylases, that are not targeted by the drug. (Image by Mary O'Reilly.)