Famesyl group

Replacement of the famesyl group by lipid analogues could be performed for full length Ras proteins in vitro by means of the enzyme famesyltrans-ferase. When such partially modified Ras constructs were applied in Xenopus oocytes the cellular machinery completed modification (endoprotease activity, carboxymethylation and palmitoylation). In these cases the H-Ras famesyl group could be stripped off most of its isoprenoid features that distinguish it from a fatty add without any apparent effect on its ability to induce oocyte maturation and activation of mitogen-activated protdn kinase In contrast, replacement by the less hydrophobic isoprenoid geranyl causes severely delayed oocyte activation. 

Displacing the Essential Metal Ion in Biomolecules. It is estimated that approximately one third of all enzymes require metal as a cofactor or as a structural component. Those that involve metals as a structural component do so either for catalytic capability, for redox potential, or to confer steric arrangements necessary to protein function. Metals can cause toxicity via substitution reactions in which the native, essential metal is displaced/replaced by another metal. In some cases, the enzyme can still function after such a displacement reaction. More often, however, enzyme function is diminished or completely abolished. For example, Cd can substitute for Zn in the protein famesyl protein transferase, an important enzyme in adding famesyl groups to proteins such as Ras. In this case, Cd diminishes the activity of the protein by 50%. Pb can substitute for Zn in 8-aminolevulinic acid dehydratase (ALAD), and it causes inhibition in vivo and in vitro. ALAD contains eight subunits, each of which requires Zn. Another classic example of metal ions substituting for other metal ions is Pb substitution for Ca in bones. 

A 3-fold exposition of the value of the AcOZ was presented in a synthesis of the lipohexapeptide C-terminus of the human Ras-protein — a protein implicated in growth-factor mediated transduction of extracellular signals across the cell membrane [Scheme 8.65].163 The challenge in a synthesis of 65.8 is the lability of the 5-famesyl group (incompatible with acid conditions used to remove Boc groups) and the S-palmitoyl group (spontaneous hydrolysis at pH 6-7), In... 

Up to now, the only bibenzyl possessing a famesyl group (180) was isolated from an unidentified Radula species and the structure established as shown in Fig. (8) [104]. 

Famesyl groups are produced in the same biosynthetic pathway as cholesterol both are derived from a building block called mevalonic acid (Figure 2). In this pathway, the 15-carbon compound, famesyl pyrophosphate, is produced, and this is dimerized to give the 30-carbon product squalene, which is converted into cholesterol. As will be described below, famesyl pyrophosphate is the source of the famesyl group in farnesylated peptides and proteins. 

The famesyl group of famesyl pyrophosphate is the simplest sesquiterpenoid and is formed by condensation of 3 isoprene units in the... 

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