Artificial substrates for prenyltransferase

Four out of 16 new allylic pyrophosphates synthesized were found to be artificial substrates for liver prenyltransferase (EC 2.5.1.1). These were the trans-and the cis-3-ethyl-3-methylallyl, the 3,3-diethylallyl and the (mixture of cis and trans) 3-methyl-3-n-propylallyl pyrophosphates. The products synthesized from these substrates and isopentenyl pyrophosphate were the appropriate homo- and bishomo-farnesyl pyrophosphates. Substitution of 3,3-dimethylallyl pyrophosphate at C-2 with a methyl group destroyed its reactivity with the enzyme. Neither the unsubstituted allyl pyrophosphate nor the cis- or trans-3-methylallyl pyrophosphate could be condensed with isopentenyl pyrophosphate. Thus the simplest allylic substrate for prenyltransferase is 3,3-dimethylallyl pyrophosphate.