Lipid lateral segregation driven by diacyl cyclodextrin interactions at the membrane surface.

Cyclodextrins are hydrophilic molecular cages with a hydrophobic interior allowing the inclusion of water-insoluble drugs. Amphiphilic cyclodextrins obtained by appending a hydrophobic anchor were designed to improve the cell targeting of the drug-containing cavities through their liposome transportation in the organism. After insertion in model membranes, they were found to induce a lateral phase separation into a pure lipid phase and a fluid cyclodextrin-rich phase (L(CD)) with reduced acyl chain order parameters, as observed with a derivative containing a cholesterol anchor (M. Roux, R. Auzely-Velty, F. Djedaïni-Pilard, and B. Perly. 2002. Biophysical Journal, 8:813-822). We present another class of amphiphilic cyclodextrins obtained by grafting aspartic acid esterified by two lauryl chains on the oligosaccharide core via a succinyl spacer. The obtained dilauryl-beta-cyclodextrin (betaDLC) was inserted in chain perdeuterated dimyristoylphosphatidylcholine (DMPC-d54) membranes and studied by deuterium NMR ((2)H-NMR). A laterally segregated mixed phase was found to sequester three times more lipids than the cholesteryl derivative (approximately 4-5 lipids per monomer of betaDLC), and a quasipure L(CD) phase could be obtained with a 20% molar concentration of betaDLC. When cooled below the main fluid-to-gel transition of DMPC-d54 the betaDLC-rich phase stays fluid, coexisting with pure lipid in the gel state, and exhibits a sharp transition to a gel phase with frozen DMPC acyl chains at 12.5 degrees C. No lateral phase separation was observed with partially or fully methylated betaDLC, confirming that the stability of the segregated L(CD) phase was governed through hydrogen-bond-mediated intermolecular interactions between cyclodextrin headgroups at the membrane surface. As opposed to native betaDLC, the methylated derivatives were found to strongly increase the orientational order of DMPC acyl chains as the temperature reaches the membrane fluid-to-gel transition. The results are discussed in relation to the "anomalous swelling" of saturated phosphatidylcholine multilamellar membranes known to occur in the vicinity of the main fluid-to-gel transition.

Hydration of black foam films made of amphiphilic cyclodextrins.

We investigate the interfacial behavior of a new type of amphiphilic cyclic oligosaccharide obtained by grafting a phospholipid onto a methylated cyclodextrin. These compounds are able to form stable black foam films, the structure of which can be determined using X-ray reflectivity. These films consist of a highly hydrated bilayer of modified cyclodextrins which are remarkably thick due to their abundant hydration core. In the present paper, we explore the influence of cyclodextrin hydration on the film structure. The hydration rate of the films is tuned by changing the cyclodextrin methylation, by binding the modified cyclodextrins to various molecules (complex formation) and by exposing the films to IR radiation. In addition, we show that the gas permeability of these phospholipidyl-cyclodextrin films is governed by their central layer of bound water, which is an efficient barrier against gas permeation.

Structural identification of new glycolipids based on cyclodextrin using high-resolution positive and negative electrospray ionization mass spectrometry.

In the continuing challenge to increase the performance of cyclodextrins (CDs) for various applications, new phospholipidyl-cyclodextrin derivatives showing improved self-organization properties in water have been synthesized, as new carriers for drug vectorization, starting from natural beta-cyclodextrin. Due to the important chemical modifications of the original cyclic oligosaccharide molecules, simple nuclear magnetic resonance (NMR) experiments do not easily lead to both an unambiguous assignment of the structures and to a rapid evaluation of the purity of the final products. However, positive and negative ion electrospray ionization (ESI-MS) in combination with accurate mass measurements and tandem mass spectrometry (MS/MS) led to the positive structural identification of the first series of these new amphiphilic compounds.

Beta-anomeric selectivity in the glycosidation of D-mannofuranurono-6,3-lactone catalyzed by boron trifluoride diethyl etherate.

The BF3-promoted glycosylation of D-mannofuranurono-6,3-lactone with dodecanol or methanol afforded n-alkyl beta-D-mannofuranosidurono-6,3-lactone. Reduction of n-dodecyl beta-D-mannofuranosidurono-6,3-lactone with sodium borohydride yielded the corresponding alkyl beta-D-mannofuranoside.