Palmitoyl group

FIGURE 25.20 Triacylglycerols are formed primarily by the action of acyltransferases on mono- and diacylglycerol. Acyltransferase in E. coli is an integral membrane protein (83 kD) and can utilize either fatty acyl-CoAs or acylated acyl carrier proteins as substrates. It shows a particular preference for palmitoyl groups. Eukaryotic acyltransferases nse only fatty acyl-CoA molecnles as substrates. 

FIGURE 49-3 Proposed transmembrane disposition of bovine rhodopsin. Sugar moieties at asparagine-2 and asparagine-15 are shown with red arrows. Palmitoyl groups at cysteine-322 and cysteine-323 are indicated with broken lines. Hydroxyamino acid residues that may be phosphorylated by rhodopsin kinase are clustered in a C-terminal domain of the molecule. 

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. 

By means of this method, a variety of Ras proteins with different lipidation patterns could be synthesized in multimilligram amounts. For instance, proteins were generated with the natural lipid combination, i.e. a farnesyl thioether and a palmitoyl thioester. Furthermore, analogous proteins were synthesized embodying only one lipid residue in which either the farnesyl- or the palmitoyl group was replaced by a stable hexadecyl thioether. In addition, proteins were built up containing a serine instead of a cysteine residue at the critical sites which normally are lipidated. In a further series of experiments, lipidated Ras proteins which carry a fluorescent Mant group incorporated into the farnesyl-type modification were synthesized.1251... 

Johansson, J., Persson, P., Lowenadler, B., Roberston, B., Joemvall, H., and Curstedt, T. (1991). Canine hydrophobic surfactant plypeptide sp-c. A lipopeptide with one thioester-linked palmitoyl group. FEES Lett. 281, 119-122. 

In line with the above-mentioned reactivity of cysteine thioesters is the occurrence of a S, N-acyl shift of the palmitoyl group from the thiol side chain to the a-amino group, when this amino group is present as a free amine. 

Scheme 6.11 Synthesis of hyperbranched polyglycerol polymers with terminal palmitoyl groups.

The same hyperbranched polyglycerol modified with hydrophobic palmitoyl groups was used for a noncovalent encapsulation of hydrophilic platinum Pincer [77]. In a double Michael addition of ethyl cyanoacetate with methyl vinyl ketone, these polymer supports indicated high conversion (81 to 59%) at room temperature in dichloromethane as a solvent. The activity was stiU lower compared with the noncomplexed Pt catalyst. Product catalyst separation was performed by dialysis allowing the recovery of 97% of catalytic material. This is therefore an illustrative example for the possible apphcation of such a polymer/catalyst system in continuous membrane reactors. 

When the nucleotide-binding site of Gs (on the a subunit) is occupied by GTP, Gs is active and can activate adenylyl cyclase (AC in Fig. 12-12) with GDP bound to the site, Gs is inactive. Binding of epinephrine enables the receptor to catalyze displacement of bound GDP by GTP, converting Gs to its active form (step (2)). As this occurs, the /3 and y subunits of Gs dissociate from the a subunit, and Gsa, with its bound GTP, moves in the plane of the membrane from the receptor to a nearby molecule of adenylyl cyclase (step (3)). The Gsa is held to the membrane by a covalently attached palmitoyl group (see Fig. 11-14). 

Seven cycles of condensation and reduction produce the 16-carbon saturated palmitoyl group, still bound to ACP. For reasons not well understood, chain elongation by the synthase complex generally stops at this point and free palmitate is released from the ACP by a hydrolytic activity in the complex. Small amounts of longer fatty acids such as stearate (18 0) are also formed. In certain plants (coconut and palm, for example) chain termination occurs earlier up to 90% of the fatty acids in the oils of these plants are between 8 and 14 carbons long. 

Our efforts to carry this scheme further ran into two difficulties. First, attempts to couple a simple oxazoline to the reducing-end building block failed, apparently because of the migration of the 4-palmitoyl group to the 6 position under the influence of the acid coupling catalyst (5 ). Second, our attempts to make a suitable non-reducing building block from the 3,4-diol... 

Compound 6-Pre closely resembles the intermediates used by Kusumoto jet al. ([this volume) and by van Boeckel et al. (16) for the preparation of disaccharide oxazolines, which were then elaborated into fully phosphorylated analogs (1,4 -diphosphates). In a formal sense, therefore, the synthesis of 6-Pw effectively constitutes a synthesis, by our revised route, or the 1,4 -bisphosphate having palmitoyl groups at positions 2, 3, 2, and 6. An additional palmitoyl group could be attached at position 4 if desired. 

In addition, esters of dextran-bearing palmitoyl groups and phosphate functions can be used for the preparation of specifically modified liposomes, which are exploited for the entrapment of peptides such as hirudin, the most potent inhibitor of thrombin [105]. 

Tripalmitoin (glycerol plus three palmitates in ester linkage) has a molecular weight of 885, so 1 kg of tripalmitoin contains (1.0 kg)(l,000 g/kg)/(885 g/mol) = 1.1 mol. Complete oxidation of the three palmitoyl groups will produce... 

Fig. 13-4 Transport of palmitoyl groups between the cytoplasm and the mitochondrial matrix. I and II are two carnitine palmitoyltransferases. The carriers transport palmitoylcarnitine across the membrane inward, and free carnitine is transported across the membrane outward. Free CoA is not transported.

Initial modification of the acyl side chain yielded FR131535.11 The synthesis of this novel echinocandin-like lipopeptide is outlined in Figure 15.5. The palmitoyl group was removed from FR901379 by treating it with acylase from Actinoplanes utahensis, which yielded FR179642. A new acyl side chain was prepared starting with 1-bromooctane and 4-hydroxybenzoic acid. 

In general, the aromatic residues tryptophan and tyrosine on the exposed surfaces of membrane proteins have a high propensity for the membrane-aqueous interface (Reithmeier, 1995 Yau et al., 1998). Of the 10 solvent-accessible ( /sa > 0.15) tryptophan and tyrosine residues in rhodopsin, 8 are located within the membrane-aqueous interfaces predicted from SDSL and bilayer thickness data. Finally, the arrangement of rhodopsin and the bilayer shown in Fig. 17 places the palmitoyl groups at C322 and C323 (shown in green in Fig. 17B) in an ideal position to be solvated by the bilayer. 

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... 

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