R115777 [(B)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)-methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone] is a potent and selective inhibitor of farnesyl protein transferase with significant antitumor effects in vivo subsequent to oral administration in mice. In vitro, using isolated human farnesyl protein transferase, R115777 competitively inhibited the farnesylation of lamin B a...

R115777 {(B)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone} is a potent and selective inhibitor of farnesyl protein transferase with significant antitumor effects in vivo subsequent to oral administration in mice. In vitro, using isolated human farnesyl protein transferase, R115777 competitively inhibited the farnesylation of lamin B an...

Isoprenoids are diverse compounds that have their biosynthetic origin in the initial condensation of isopentenyl diphosphate and dimethylallyl diphosphate to form C10 prenyl diphosphates that can be elongated by the addition of subsequent isopentenyl diphosphate units. These reactions are catalyzed by either cis-prenyltransferases (CPTs) or trans-prenyltransferases. The synthesis of volatile te...

Dalopius marginatus (L.) (Coleoptera: Elateridae) is a very common click beetle species developing in forest soils an area from southwest Europe to eastern Siberia. Here, we studied the composition of female-released sex pheromone D. using coupled gas chromatography-mass spectrometry (GC-MS). Neryl octanoate, neryl decanoate, and dodecanoate, ratio approximately 1:100:3, were only volatile comp...

Pepticinnamins A, B, C, D, E and F, a family of farnesyl-protein transferase (FPT) inhibitors were isolated from the fermentation broth of Streptomyces sp. OH-4652. These inhibitors were purified from whole broth by extraction with chloroform, followed by silica gel column chromatography, Sephadex LH-20 chromatography and reverse phase HPLC. Among these, pepticinnamin C showed the most potent i...

N-Acetyl-S-farnesyl cysteine (AFC) is the minimal synthetic substrate for the enzyme Icmt, which methylates prenylated proteins. The desthio-AFC isostere 2 has been synthesized in racemic form. This analog was not an Icmt substrate, but instead a weak inhibitor with an IC50 of approximately 325 microM.

Regioselective halogenation of the terminal isopropylidene unit of different acyclic polyolefinic polyprenoids (farnesyl acetate, geranylgeranyl acetate, squalene, etc.) using NCS/catalytic polymer-supported selenenyl bromide is described; good to excellent yields are obtained (68-96%). The first applications of this protocol include the concise synthesis of bioactive terpenoids 1-3.

Isoprenoids are diverse compounds that have their biosynthetic origin in the initial condensation of isopentenyl diphosphate and dimethylallyl diphosphate to form C10 prenyl diphosphates that can be elongated by the addition of subsequent isopentenyl diphosphate units. These reactions are catalyzed by either cis-prenyltransferases (CPTs) or trans-prenyltransferases. The synthesis of volatile te...

UNLABELLED Farnesyl pyrophosphate synthase (FPS; EC 2.5.1.10) is a key enzyme in isoprenoid biosynthetic pathway and provides precursors for the biosynthesis of various pharmaceutically important metabolites. It catalyzes head to tail condensation of two isopentenyl pyrophosphate molecules with dimethylallyl pyrophosphate to form C15 compound farnesyl pyrophosphate. Recent studies have confirme...

We have previously shown that protein prenylation occurs in the Trypanosomatids Trypanosoma brucei (T. brucei), Trypanosoma cruzi, and Leishmania mexicana and that protein farnesyltransferase (PFT) activity can be detected in cytosolic extracts of insect (procyclic) form T. brucei. A PFT that transfers the farnesyl group from farnesyl pyrophosphate to a cysteine that is 4 residues upstream of t...