Isoprenyl

Since the vinyl-C//proton at (<5//= 6.33 shows no additional V////couplings apart from the doublet of doublets splitting (cis and trans coupling), the side-chain is a 1-isoprenyl chain E and not a 1-methylbuta-l,3-dienyl residue F. 

Chemistry and biosynthesis of isoprenylated flavonoids from moraceous plant 99PAC1116. 

Lipidation -acylation TV -myristoylation Myristoy-lation S-prenylation Prenylation Palmitoylation Isoprenylation GPI anchors Glypiation... 

PPCs Prenylation is the post-translational addition of 15- or 20-carbon isoprenyl lipids to the C-terminus of proteins. Prenylation is an irreverable modification that anchors proteins to the membrane fraction of cells. 

All small GTPases (except Ran) are post-translationally modified. Most important is the isoprenylation of the C-terminus. The type of modification is determined by... 

Many GPCRs contain one or more conserved cysteine residues within their C-terminal tails, which are modified by covalent attachment of palmitoyl or isoprenyl residues. The palmitoyl moiety is anchored in the lipid bilayer forming a fourth intracellular loop. There is evidence that palmitoylation of a GPCR is a dynamic process and may affect receptor desensitization. 

Nomura T. The Chemistry and Biosynthesis of Isoprenylated Flavonoids From Moraceous Plants Pwre A/y)/. Chem. 1999 77 1115-1118... 

Reduction of the isoprenyl groups of isohumulone and p-isohumulone to tetrahydro- and hexahydro-isohumulone, respectively, increases the lipophilicity of the resultant products. A corresponding increase in their bitterness was observed. A similar increase in bitterness was reported for hydroquinine following reduction of the vinylic double bond of quinine (117). Because the stereochemistry of the quinines does not have any significant effect on the bitterness, this change must be due to change in the relative lipophilicity of the compound. 

Figure 5.41 Heteronuclear shift correlation (HETCOR) spectrum of an isoprenyl-coumarin.

The DQF (double-quantum filtered)-COSY spectrum of an isoprenyl coumarin along with H-NMR data are shown. Determine the H/ H homonuclear interactions in the DQF-COSY spectrum. 

The LR COSY-45° spectrum and H-NMR chemical shifts of an isoprenyl coumarin are given below. Determine the long-range H/ H homonuclear correlations based on the long-range COSV45° spectrum. Demonstrate with reference to problem -5.15 how they can be helpful in interconnecting different spin systems ... 

Flavonoids Flavonoids Flavonoid glycosides Isoprenylated flavones... 

Based on the extraordinary selectivity in hydrosilylation reactions when an alkyne competes with other groups for a silicon-bonded active hydrogen, further derivatisation can be carried out. The hydrosilylation of 2-methyl-3-butynol, which works very well with polymeric siloxanes, gives hydroxyal-kenylsilicon compounds - a l-silylalkenyl/2-silylalkenyl mixture from cis-addition across the triple bond. Elimination of water from the tert. alcohol produced, catalyzed by traces of a strong acid, results in isoprenylic siloxanes in more than 90 % overall yield (Eq. 8). 

Dienes bonded to silicones to give products stable to hydrolysis are available in a wide variety of combinations, from the distillable l,3-bis(isoprenyl)-l,l,3,3-tetramethyldisiloxane to high polymers with dozens of diene groups attached [23], Diels-Alder cycloadditions may be performed with dieno-philes. Maleic anhydride adds almost quantitatively to the conjugated diene system, giving easy access to a siloxane species of considerable industrial importance [24]. 

Brown s synthesis of 34 and 35 utilized -2 -isoprenyldi-Z-isopinocam-pheylborane B as a reagent for asymmetric isoprenylation of aldehydes as shown in Scheme 50 [76]. 

Diamino-2,l,3-benzothiadiazole 82 affords [l,2,5]selenodiazolo[3,4-i ]-2,l,3-benzothiadiazole 83 quantitatively on treatment with selenium oxychloride in refluxing chloroform-pyridine <2004JHC955>. This was an improvement of the previous method using selenium dioxide (62% yield) <1984ZNB485>. 6-Isoprenyl-477-imidazo[4,5-< ]-benzothiadiazolone 84 was obtained when 4,5-diaminobenzothiadiazole was reacted with methyl acetoacetate in xylene at reflux (Scheme 10) <1997H(45)19>. 

GDP-dissociation inhibitors Bind isoprenylated Rab proteins in the GDP-bound form, resulting in a cytoplasmic complex. 

G protein y subunits are modified on their C-terminal cysteine residues by isoprenylation [26,27]. There is now strong evidence that this modification plays a key role in anchoring the ysubunit and its associated P subunit to the plasmalemma. The importance of this anchoring is illustrated in Figure 19-2, which shows that the ability of py subunits to direct GRKs to ligand-bound receptors depends on this membrane localization. 

Rab is a family of small G proteins involved in membrane vesicle trafficking. Mammalian tissues contain around 30 forms of Rab, which specifically associate with the various types of membrane vesicles and organelles that exist in cells [30,31]. Rab proteins, named originally as ras-related proteins in brain, are isoprenylated and associate with membranes, as do isoprenylated Ras and G protein y subunits. However, unlike these other G proteins, the GTP and GDP binding to Rab appears to regulate its association with membrane compartments. 

There are multiple isoforms of the a and p subunits of soluble GC that exhibit distinct tissue and cellular distributions. Most of the isoforms are expressed in brain, including 0Ci 3 and and P3. The p2 subunit is found primarily in lung. This isoform also contains a consensus sequence at its carboxy terminus for isoprenylation or carboxymethyl-ation, which could serve to anchor the protein to the plasma membrane. It has been proposed that specific isoforms of the a and P subunits of GC may form heterodimers with distinct functional and regulatory properties, although this remains to be established with certainty. 

A first approach to study the interaction of posttranslational modified Ras proteins with membranes was the analysis of binding and exchange of isoprenyl-ated peptides with and between lipid vesicles utilizing a fluorescent bimanyl label. Studies with K-Ras peptides revealed that a single isoprenyl group is sufficient for membrane association only if supported by carboxymethylation of the C-terminal cysteine [227,228]. 

The H- and N-isoforms of Ras support the first (isoprenoid) hydrophobic modification by additional thioester formation with palmitoylic acids [18]. At physiological temperature (37°C) the dissociation of doubly modified lipo-peptides with an isoprenyl thioether and a palmitoyl thioester is very slow and characterized by half-times in the order of 50 h. Here, the relative effect of the carboxymethylation is significantly reduced. Palmitoyl groups with their C16 alkane chain length contribute more efficiently to membrane anchoring than the farnesyl modification. 

The low percentage of obtaining products belonging to the a-kainic acid series (at best 50%) was attributed to unfavorable transition states with repulsion between one of the aminomalonate ester groups and the isoprenyl chain. These difficulties were circumvented by using a simple a-amino ester (131) in lieu of the aminomalonate group this has led to a simple synthesis of a-kainic acid (Scheme 33) (178). 

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