Cholesterol self-association

One factor determining toxicity of AmB formulations is the form in which the antibiotic is released monomeric or aggregated because only self-associated AmB can complex cholesterol in eukaryote membranes (25). The differential toxicity of the lipid formulations toward macrophages could be related to their stability in the culture medium. For example, the Ampho-liposome formulation, which is destabilized in the presence of serum (24), has... 

Bolard J, et al. One-sided action of amphotericin B on cholesterol-containing membranes is determined by its self-association in the medium. Biochemistry 1991 30 5707. 

Some works were reported in which thermosensitive polymers were conjugated with hydrophobic groups. End-capping random poly(NIPA-co-dimethylacrylamide) [55] and grafting poly(NIPA-co-hydroxymethylacryl-amide) [56] with cholesterol moieties led to self-associating polymers with different morphologies. By dissolution of the copolymers in dimethylfor-... 

Yusa S.-I., Kamachi M., Morishima Y. Hydrophobic self-association of cholesterol moieties covalently linked to polyelectrolytes effect of spacer bond. Langmuir 1998 14 6059-6067. 

As noted above, MeC trimerizes and MeLC does not self-associate in CHCI3. Under these conditions, Foster et al. [202] used vapor pressure osmometry to show that solubilized cholesterol (which dimerizes in CHCI3 [203]) heteroassociated with MeC but not with MeLC. The result was a 1 1 mixed dimer complex of cholesterol and MeC with a molar free energy of formation which was 33% that for the trimerization of MeC in the same solvent [202]. The bonding is presumably via the 3-hydroxyl functions in both steroids this interaction may be of potential importance in the binding of cholesterol to bile acids and salts within membranes and mixed micelles. 

Another important mechanism of vesicle-mediated transport is defined by the structural protein caveolin. Caveolins are a family of integral membrane proteins that self-associate and also specifically bind to cholesterol and glycosphingolipids in a relatively stable microdomain. These microdomains are an important... 

Very little is yet known about how phospholipid binds to apo A1 in native HDL (Chapter 17). Studies of lipid binding by wild type and mutant apo A1 species in vitro suggested important roles for the first (N-terminal) and last (C-terminal) amphipathic helical repeats. Until recently, mature apo A1 isolated from serum HDL by delipidation, urea-denaturation, and dialysis was widely used as a surrogate for native lipid-free apo A1 and/or pre-beta,-HDL. It has become clear, however, that these molecules differ significantly in physical properties. For example, serum-derived apo A1 self-associates whereas pre-beta,-HDL does not. Serum-derived apo A1 can completely unfold to seal the edge of discoidal recombinant particles containing large amounts of phospholipids and cholesterol. In contrast pre-beta,-HDL is not converted to discoidal HDL by additional phospholipid transfer. 

Parker and Bhaskar (1968) have used infrared measurements of the OH-stretching band of cholesterol to study the self-association of this compound in carbon tetrachloride. At concentrations below 0.014M, cholesterol exists only as a monomer, as shown by a single sharp band at 3620 cm due to the OH-stretching vibration of the free molecule (Fig. 14). As the concentration is increased, a new broad band appears on the low-frequency side at 3470 cm " in addition to the monomer band at 3620 cm" The 3470 cm" band is due to the bonded OH group of the dimer. As the concentration is increased, a third band appears at 3330 cm" in addition to the monomer and dimer bands and is probably due to a trimer or higher aggregate. At a concentration of 0.2M the dimer band is observed only as a shoulder on the 3330 cm" band. 

Parker and Bhaskar (1968) have measured quantitatively the self-association by hydrogen bonding of cholesterol (use of the O—H stretching bands), and the inter-molecular hydrogen bonding between cholesterol and several triglycerides by infrared... 

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