SYNTHESIS AND EVALUATION OF BENZOPHENONE-BASED PHOTOAFFINITY-LABELINGANALOGS OF PRENYL PYROPHOSPHATES CONTAINING STABLE AMIDE LINKAGES

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 pyrophos phate and benzophenone functionalities while 1b contains a geranyl (C- 10) moiety. Compounds 1a and 1b are competitive inhibitors of yeast fa rnesyl protein transferase with respect to farnesyl pyrophosphate and have K-I values of 6000 nM and 700 nM. Upon irradiation, [P-32]-1b pre ferentially labels the beta-subunits of yeast farnesyl protein transfe rase and human geranylgeranyl protein transferase. (C) 1997 Elsevier S cience Ltd.