Disulfide lipids

MTP is responsible for the transfer of TGs and cholesteryl esters from the endoplasmic reticulum (ER) to lipoprotein particles (VLDL in hepatocytes in the liver and chylomicrons in endocytes in the intestine) for secretion [52]. It is a heterodimer consisting of a unique large subunit essential for lipid transfer encoded by the mttp gene and a smaller subunit, the ubiquitous ER enzyme protein disulfide isomerase [53]. 

The most common type of heterobifunctional reagent used for the activation of lipid components includes the amine- and sulfhydryl-reactive crosslinkers containing an N-hydroxysuccinim-ide (NHS) ester group on one end and either a maleimide, iodoacetyl, or pyridyl disulfide group on the other end (Chapter 5, Section 1). Principle reagents used to effect this activation process include SMCC (Chapter 5, Section 1.3), MBS (Chapter 5, Section 1.4), SMPB (Chapter 5, Section 1.6), SIAB (Chapter 5, Section 1.5), and SPDP (Chapter 5, Section 1.1). Other... 

N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) also may be used to activate pure PE lipids in a similar manner to SMPB. The result will be a derivative containing pyridyl disulfide groups rather than maleimide groups (Figure 22.12). Pyridyl disulfides react with sulfhydryls to form disulfide linkages. Either the standard SPDP or the long-chain version, LC-SPDP, may be employed in the following protocol. 

Figure 5 Degradable PEG-lipid degradability via the orthoester function, the vinylether, or the disulfide group. Abbreviation PEG, poly(ethylene glycol). Source From Refs. 31, 35 0.

PEG-Lipid Bearing a Disulfide Function Within the Linker... 

Lipid transfer peptides and proteins occur in eukaryotic and prokaryotic cells. In vitro they possess the ability to transfer phospholipids between lipid membranes. Plant lipid transfer peptides are unspecific in their substrate selectivity. They bind phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and glycolipids. Some of these peptides have shown antifungal activity in vitro The sequences of lipid transfer proteins and peptides contain 91-95 amino acids, are basic, and have eight cysteine residues forming four disulfide bonds. They do not contain tryptophan residues. About 40% of the sequence adopts a helical structure with helices linked via disulfide bonds. The tertiary structure comprises four a-helices. The three-dimensional structure of a lipid transfer peptide from H. vulgare in complex with palmitate has been solved by NMR. In this structure the fatty acid is caged in a hydrophobic cavity formed by the helices. 

This selenium-dependent enzyme [EC 1.11.1.9] catalyzes the reaction of two molecules of glutathione with hydrogen peroxide to produce glutathione disulfide and two water molecules. Hydrogen peroxide can be replaced by steroid and lipid hydroperoxides, albeit not as effectively (nevertheless, this enzyme is not identical with phospholipid-hydroperoxide glutathione peroxidase [EC 1.11.1.12]). However, the hydroperoxy products formed by the action of lipoxygenase [EC 1.13.11.12] are not substrates. 

Racemic thioglycerol (3-sulfanylpropane-l,2-diol) was used for the attachment of two lipid chains via ester bond formation with the hydroxy groups 82 while the free thiol group serves for selective cross-linking to other molecules via disulfide or sulfide bonds utilizing mild thiol-disulfide interchange or thiol addition reactions (Scheme 15).[163,164,167]... 

Fig. 8. Two pairs of a polymerizable zwitterionic dienoyl lipid and a cleavable disulfide amphiphile derived from cysteine. In each pair, one amphiphile has a hydrocarbon tail and the other a fluorocarbon tail.

The proton pump inhibitors are lipophilic weak bases (pKa 4-5) and after intestinal absorption diffuse readily across lipid membranes into acidified compartments (eg, the parietal cell canaliculus). The prodrug rapidly becomes protonated within the canaliculus and is concentrated more than 1000-fold by Henderson-Hasselbalch trapping (see Chapter 1). There, it rapidly undergoes a molecular conversion to the active form, a reactive thiophilic sulfenamide cation, which forms a covalent disulfide bond with the H +, K+ ATPase, irreversibly inactivating the enzyme. 

The aim is to extract protein molecules as pure as possible. Detergents generally help membrane proteins to dissolve and separate from lipids. Reductants are used to reduce disulfide bonds or prevent oxidation. Denaturing agents alter ionic strength... 

The C-terminal domain is a Ca2+-dependent C-type lectin (Chapter 4), while the N-terminal domain is involved in oligomer formation through disulfide bridges. The overall structure is similar to that of the complement protein Clq (Chapter 31).e) Protein D is also collagen-like1 but evidently plays a very different functional role than SP-A. The latter associates with the major surfactant lipids but SP-D does not. It does bind phosphatidyl inositol" and gluco-sylceramide, lipids that are present in small amounts. Perhaps SP-D helps to remove these polar lipids which might interfere with surfactant action.6 Both proteins A and D may also have functions in the immune system.1... 

Proteins SP-B and SP-C are small extremely hydrophobic polypeptides consisting of 79 and 35 amino acid residues, respectively." 0 Aliphatic branched amino acids constitute 23 of the 35 residues of the C-terminal part of protein C, which is also palmitoylated on two cysteine residues. SP-B is formed from a large 381-residue precursor. The mature protein contains seven cysteines and disulfide bridges. Both proteins have major effects on the properties of the surfactant mixture. They promote rapid reorganization of lipid layers, an important consideration for the functioning of the surfactant. Infants lacking SP-B suffer severe respiratory failure with high mortality.6... 

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