Fig. 1. Ligand-directed dibromophenyl benzoate (LDBB) chemistry for rapid and selective intracellular protein labeling. (a) Schematic illustration of LDBB chemistry for chemical labeling of a protein of interest (POI) in living cells. (b) Design strategy for intracellular protein acylation; the reactivity was tuned at position A (ortho-substituted phenyl ester moiety), and the stability was tuned at positions A and B (probe moiety). (c) Chemical structures of reagents 1–6 for eDHFR containing TMP ligand and fluorophores, which were linked with various phenyl ester linkers (or acyl imidazole-type reagent 7).