Ligand-protein binding assays based on intrinsic protein fluorescence are straightforward, inexpensive methods to study ligand-protein interactions. However, their applicability is limited to ligands that can interfere with protein emission. In this Note, we describe the applicability of 2,2'-bithiophene as a FRET-based sensor tag, that can be incorporated into high-affinity ligands to generate target-specific compounds able to quench protein fluorescence upon binding. The generated ligands …