Synthesis of (S)-Isoprenoid Thiodiphosphates as Substrates and Inhibitors
| Autor: | Richard M. Phan, Poulter Cd |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Tris
Stereochemistry Thiophosphate Birds chemistry.chemical_compound Hemiterpenes Organophosphorus Compounds Farnesyl diphosphate synthase Polyisoprenyl Phosphates Animals Carbon Radioisotopes Enzyme Inhibitors Pyrophosphatases Incubation chemistry.chemical_classification biology Chemistry Organic Chemistry Terpenoid Trimethyl phosphate Kinetics Enzyme Thiopyrophosphate biology.protein lipids (amino acids peptides and proteins) Sesquiterpenes |
| Zdroj: | The Journal of Organic Chemistry. 66:6705-6710 |
| ISSN: | 1520-6904 0022-3263 |
| DOI: | 10.1021/jo010505n |
| Popis: | Thiolo thiophosphate analogues of isopentenyl diphosphate (IPP), dimethylallyl diphosphate (DMAPP), geranyl diphosphate (GPP), farnesyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP) were synthesized. Inorganic thiopyrophosphate (SPP(i)) was prepared from trimethyl phosphate in four steps. The tris(tetra-n-butylammonium) salt was then used to convert isopentenyl tosylate to (S)-isopentenyl thiodiphosphate (ISPP). (S)-Dimethylallyl (DMASPP), (S)-geranyl (GSPP), (S)-farnesyl (FSPP), and (S)-geranylgeranyl thiodiphosphate (GGSPP) were prepared from the corresponding bromides in a similar manner. ISPP and GSPP were substrates for avian farnesyl diphosphate synthase (FPPase). Incubation of the enzyme with ISPP and GPP gave FSPP, whereas incubation with IPP and GSPP gave FPP. GSPP was a substantially less reactive than GPP in the chain elongation reaction and was an excellent competitive inhibitor, K(I)(GSPP) = 24.8 microM, of the enzyme. Thus, when ISPP and DMAPP were incubated with FPPase, GSPP accumulated and was only slowly converted to FSPP. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|