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

Article abstract of DOI:10.1016/S0960-894X(97)00373-9

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 (C₅) unit between the phyophosphate and benzophenone functionalities while 1b contains a geranyl (C₁₀) 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 [³²P]-1b preferentially labels the β-subunits of yeast farnesyl protein transferase and human geranylgeranyl protein transferase.