Analogs of farnesyl pyrophosphate incorporating internal benzoylbenzoate esters: Synthesis, inhibition kinetics and photoinactivation of yeast protein farnesyltransferase

Abstract The syntheses of two analogs ( 1a and 1b ) of farnesyl pyrophosphate incorporating photoactive benzoylbenzoate esters are described. Both 1a and 1b are competitive inhibitors of yeast protein farnesyltransferase with respect to farnesyl pyrophosphate and have Ki values of 3300 nM and 880 nM, respectively. Upon photolysis for two hours, 1a and 1b inactivate the enzyme by 46% and 11%, respectively. These compounds should be useful for a variety of studies of protein prenyltransferases.