Prenyl groups

The intramolecular insertion of an internal alkyne into an aryl or alkenyl halide 727 generates aryl- or alkenylpalladium as an intermediate, which is trapped with an organozinc or organostannane to give 728. Overall cis addition to the alkyne takes place[595,596]. The reaction of the alkenylstannane 730 with the 2-bromomethylfuran 729 is used for the introduction of a prenyl group[597]. 

Figure 13-1. The chemical structure of a prenyl group. N can be 0 (dimethylallyl), 1 (geranyl), 2 (farnesyl), 3 (geranylgeranyl), etc...

Some proteins can be posttranslationally modified by the addition of prenyl groups. Prenyl groups are long-chain, unsaturated hydrocarbons that are intermediates in isoprenoid synthesis. The farnesyl group has 15 carbons, and the geranylgeranyl has 20 carbons. They are attached to a cysteine residue near the end of the protein as a thiol ether (Protein-S-R). Other proteins can have a long-chain fatty acid (C14=myristoyl, C16=palmitoyl) attached to the amino terminus as an amide. These fatty acid modifications can increase the association of proteins with the membrane. 

The y-subunit contains a characteristic CAAX motif, which allows covalent attachment of prenyl groups and anchors the protein to the inner surface of the membrane. 

The synthesis of lipidated peptides is implicated by the base-lability of the thioester and the acid sensitivity of the prenyl group double bonds. Thus, new protecting groups are required which can be removed under extremely mild, preferably neutral, conditions. 

Hi) Synthesis of S-prenylated peptides Various syntheses of S-prenylated peptides " have relied on the assembly of the peptide backbone on the solid phase, using standard protocols, and subsequent S-prenylation in solution. As a consequence, any final deprotection steps of other amino acids after the S-prenylation cannot be performed under strongly acidic conditions due to the acid lability of the prenyl group. The prenylation reactions themselves can he carried out under basic or mildly acidic conditions. Typical synthesis problems that arise during the S-alkylation are (1) incomplete conversion because of solubility problems, (2) oxidation of the thiol group to disulfides under basic conditions, (3) formation of the sulfonium... 

The UV spectrum (7max 225,242,253,276,289, and 351 nm) of clausine D (29) was similar to that of O-demethylmurrayanine (24), which also represents a 3-formyl-l-hydroxycarbazole framework. The presence of a hydroxy group and a conjugated aldehyde group was further supported by strong absorptions at 3380 and 1655 cm in the IR spectrum. The H-NMR spectrum was very similar to that of O-demethylmurrayanine, except for the presence of a prenyl group ( 1.65,... 

Prenyltransferases are a class of enzymes that transfer allylic prenyl groups to acceptor molecules. Prenyl transferases commonly refer to prenyl diphosphate synthases (even though the class of prenyl transferases also includes enzymes that catalyze the transfer of prenyl groups to acceptors that include not only isopentenyl diphosphate (IPP) but also aromatic compounds and proteins etc.). 

It is well-established that in the case of short lipid chains such as famesyl and myristoyl, the binding affinity of monolipidated proteins to membranes, is not sufficient to promote stable association. 25 26 36 8°1 Among the various intracellular proteins that are covalently modified by an acyl group from a fatty acid or a prenyl group, several carry more than one such hydrophobic substituent per protein molecule. The addition of a second hydrophobic chain to a... 

A related compound to 79, but containing two double bonds in one of the prenyl groups, is 5,7-dihydroxy-4 -methoxy-3 -C-(3-methylbut-l,5-dienyl)-5 -C-prenylflavanone (burttinone-dehydrate, 78), also isolated from E. burttii. ... 

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