Transbilayer complementarity of phospholipids in cholesterol-rich membranes.

Lipid-lipid interactions across cholesterol-rich phospholipid bilayers were investigated by measuring nearest-neighbor preferences of exchangeable phospholipids derived from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), in the presence of nonexchangeable dimers (i.e., templates) made from DMPE or DSPE.

A quantitative assessment of the influence of permanent kinks on the mixing behavior of phospholipids in cholesterol-rich bilayers.

The mixing behavior of a phospholipid containing a cis-cyclopropyl moiety (1) with one that contains two myristoyl groups (3a) has been investigated in fluid bilayers via the nearest-neighbor recognition (NNR) method. In the absence of cholesterol, these lipids mix ideally. In the presence of cholesterol, they show a modest preference for homo-phospholipid association.

Probing the hydration of lipid bilayers using a solvent isotope effect on phospholipid mixing.

Nearest-neighbor recognition experiments, which have been carried out using exchangeable dimers derived from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine,and 1-palmitoyl-2-oleoyl-sn-glycerophosphoethanolamine, indicate that replacement of H2O by D2O can significantly influence phospholipid mixing, but only in bilayers that are saturated and devoid of cholesterol. These findings, together with those of previous electron spin resonance spin-labeling studies,indicate that mammalian membranes, which are rich in cholesterol and unsaturated phospholipids, are ideal hydrophobic barriers.

Detection of unusual lipid mixing in cholesterol-rich phospholipid bilayers: the long and the short of it.

Nearest-neighbor recognition studies have revealed that favored sterol-phospholipid associations can be reversed in a fluid bilayer that contains relatively long (high melting) and short (low melting) phospholipids, when the sterol content is sufficiently high; that is, like-lipids now become favored nearest-neighbors. A possible origin of this effect is briefly discussed.

Transbilayer complementarity of phospholipids. A look beyond the fluid mosaic model.

Lipid-lipid interactions across a phospholipid bilayer were probed by measuring the nearest-neighbor preferences of exchangeable phospholipid monomers derived from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) in the presence of nonexchangeable DMPE- or DSPE-based dimers. Each of these permanent dimers promoted homophospholipid association to the same extent, whereas the corresponding nonexchangeable monomers were without effect. These results support a model in which the longer phospholipids in one monolayer leaflet preferentially associate with shorter ones in the adjoining monolayer.

Unraveling the mystery surrounding cholesterol's condensing effect.

The results of nearest-neighbor recognition experiments that have been carried out with exchangeable dimers derived from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, in the presence of cholesterol, dihydrocholesterol, coprostanol, cholestane, cholesteryl methy ether, and sitosterol, provide strong support for a condensing mechanism in which the flexible acyl chains of the phospholipids complement, perfectly, the shape of neighboring sterols, thereby leading to a high number of hydrophobic contacts and tight packing.

Quantifying the effects of deuterium substitution on phospholipid mixing in bilayer membranes. A nearest-neighbor recognition investigation.

Nearest-neighbor recognition measurements have established that the effects of deuterium substitution on phospholipid mixing are exceedingly small. Thus, the mixing behavior of an exchangeable phospholipid bearing two stearoyl chains with a homologue containing two myristoyl chains in gel-fluid bilayers, fluid bilayers, cholesterol-rich fluid bilayers, and gel-fluid bilayers that have been enriched with cholesterol correspond to a difference in the free energy of mixing that is less than 2.2 cal/mol of hydrogen in all cases.

Recognition of a cysteine substrate by E. coli gamma-glutamylcysteine synthetase probed by sulfoximine-based transition-state analogue inhibitors.

A series of sulfoximine-based transition-state analogue inhibitors with a varying alkyl side chain was synthesized to probe the recognition of a Cys substrate by E. coli gamma-glutamylcysteine synthetase (gamma-GCS). The sulfoximines with a small alkyl group (H, methyl, ethyl, propyl, butyl and CH2OH) each served as a slow-binding inhibitor, the sulfoximine with an ethyl being by far the most potent inhibitor to cause facile and irreversible enzyme inhibition.