| Abstract
| - Thiolo thiophosphate analogues of isopentenyl diphosphate (IPP), dimethylallyl diphosphate(DMAPP), geranyl diphosphate (GPP), farnesyl diphosphate (FPP), and geranylgeranyl diphosphate(GGPP) were synthesized. Inorganic thiopyrophosphate (SPPi) was prepared from trimethylphosphate in four steps. The tris(tetra-n-butylammonium) salt was then used to convert isopentenyltosylate to (S)-isopentenyl thiodiphosphate (ISPP). (S)-Dimethylallyl (DMASPP), (S)-geranyl (GSPP),(S)-farnesyl (FSPP), and (S)-geranylgeranyl thiodiphosphate (GGSPP) were prepared from thecorresponding bromides in a similar manner. ISPP and GSPP were substrates for avian farnesyldiphosphate synthase (FPPase). Incubation of the enzyme with ISPP and GPP gave FSPP, whereasincubation with IPP and GSPP gave FPP. GSPP was a substantially less reactive than GPP in thechain elongation reaction and was an excellent competitive inhibitor, KIGSPP = 24.8 μM, of theenzyme. Thus, when ISPP and DMAPP were incubated with FPPase, GSPP accumulated and wasonly slowly converted to FSPP.
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