Different analogues of farnesyl pyrophosphate inhibit squalene synthase and protein: Farnesyltransferase to different extents
article
The inhibitory potency of farnesyl pyrophosphate analogues was investigated on two farnesyl pyrophosphate-consuming enzymes: squalene synthase, a secondary regulation site in the cholesterol synthesis pathway, and protein: farnesyl transferase, which plays a role in the function of Ras-proteins. For the transferase determination a rapid in vitro assay, using Sepharose-bound Ras-peptides, was developed. The distinct farnesyl pyrophosphate analogues showed a different order of potency in the inhibition of these two enzymes. Using the farnesyl transferase assay with pre-p21(Ha-ras) as substrate the same result was obtained. The difference observed in the in vitro assays was also reflected in the inhibition of cholesterol synthesis, protein prenylation in general and Ha-ras farnesylation in Rat-1.H-ras-13 cells, a rat fibroblast cell line that overproduces human p21(Ha-ras). This work shows that farnesyl pyrophosphate analogues can be developed for specific inhibition of different processes such as cholesterol synthesis and protein prenylation.
Chemicals/CAS: farnesyl pyrophosphate, 13058-04-3; Oncogene Protein p21(ras), EC 3.6.1.-; p21(ras) farnesyl-protein transferase, EC 2.5.1.-; Polyisoprenyl Phosphates; Squalene Synthetase, EC 1.3.-; Transferases, EC 2.
Chemicals/CAS: farnesyl pyrophosphate, 13058-04-3; Oncogene Protein p21(ras), EC 3.6.1.-; p21(ras) farnesyl-protein transferase, EC 2.5.1.-; Polyisoprenyl Phosphates; Squalene Synthetase, EC 1.3.-; Transferases, EC 2.
Topics
TNO Identifier
232962
ISSN
00062952
Source
Biochemical Pharmacology, 49(6), pp. 839-845.
Pages
839-845
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