Didehydrofarnesyl diphosphate: an intrinsically fluorescent inhibitor of protein farnesyltransferase

Didehydrofarnesyl diphosphate (ΔΔFPP), a fluorescent pentaene analogue of farnesyl diphosphate (FPP), was synthesized using stereoselective Wittig reactions. Although ΔΔFPP was not an alternative substrate for yeast protein farnesyltransferase (FTase), the fluorescent analogue was a potent competitive inhibitor with a Ki value of 8.8 μM (Km (FPP)=27 μM).