Synthesis and evaluation of GGPP geometric isomers: divergent substrate specificities of FTase and GGTase I

A stereocontrolled synthetic route has been used to prepare two of the geometric isomers of all-trans-GGPP. Neither of these isomers is effective substrates for mammalian GGTase I, but 3 is a potent inhibitor of this enzyme (IC50=100 nM). Surprisingly, both compounds are effective substrates for mammalian FTase.