Synthesis and evaluation of benzophenone-based photoaffinity labeling analogs of prenyl pyrophosphates containing stable amide linkages

Abstract The syntheses of two photoactive prenyl pyrophosphate analogs ( 1a and 1b ) that incorporate stable amide-linked benzophenones are described. Compound 1a contains a single isoprene (C 5 ) unit between the pyrophosphate and benzophenone functionalities while 1b contains a geranyl (C 10 ) moiety. Compounds 1a and 1b are competitive inhibitors of yeast farnesyl protein transferase with respect to farnesyl pyrophosphate and have K I values of 6000 nM and 700 nM. Upon irradiation, [ 32 P]- 1b preferentially labels the β-subunits of yeast farnesyl protein transferase and human geranylgeranyl protein transferase.