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Trifluoromethyldiazirines are well established photoaffinity labels PAL used in biochemical investigations to create covalent ligandreceptor bonds. Two new diazirinylbenzoic acids 8b,cwith perfluorobutyl and perfluorooctyl chains FPAL were efficiently prepared from pbromobenzaldehyde and attached to the highly potent and specific VATPase inhibitors 21deoxyconcanolide A 2 and bafilomycin A15, deriving from the natural product pool from Streptomycesproducer strains. The labelled derivatives 17and 18were efficiently purified by fluorous solidphase extraction. Functional biochemical assays with the VATPase holoenzymes proofed strong inhibition activities. So far, radioactive isotopes or biotintags have mainly been used for tracing compounds in photoaffinity studies. The C4F9 and C8F17fluorous tags aim to enable advantageous separation and identification of labelled peptide fragments by fluorous chromatography followed by MS analysis. Therefore, FPAL represents an innovative new concept for binding site determination and should significantly accelerate and simplify such biochemical investigations.