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Steven L Regen

Publications and source records attributed to Steven L Regen.

At least 37 records · Page 2Linked to original sources
PubMed2004

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. Such transbilayer complementarity is likely to play an important role in stabilizing biological membranes and also in promoting a compositional interdependence of their two lipid leaflets.

Kinetics↗
PubMed2004

Glued Langmuir-Blodgett bilayers from porous versus nonporous surfactants.

Poly(4-styrenesulfonate) (PSS) has been used to ionically cross-link (glue together) single Langmuir-Blodgett bilayers derived from 1,2,4,5-tetrakis[N,N-dimethyl-N-(1-hexadecyl)-ammoniummethyl]benzene (2a) and tris(N,N-dimethyl-N-hexadecylammoniummethyl)mesitylene (3). The resulting films are of high quality as judged by He/N2 permeation selectivities of ca. 100. Such selectivity is well in excess of the Knudsen diffusion limit of 2.6 and approaches that which has been found for glued bilayers of 5,11,17,23,29,35-hexakis[(N,N,N-trimethylamonium)-N-methyl-37,38,39,40,41,42-hexakis-n-hexamedecyloxy-calix[6]arene hexachloride (1). The significance of these findings to LB technology, in general, is briefly discussed.

Journal Article↗
PubMed2003

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.

Cholesterol↗
PubMed2003

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. These findings provide the strongest evidence to date in support of the use of deuterated phospholipids as "nonperturbing" probes for structural and dynamic studies of bilayer membranes.

Deuterium↗
PubMed2003

Kinetic evidence for the existence and mechanism of formation of a barrel stave structure from pore-forming dendrimers.

A dendritic approach to the construction of a homologous series of pore-forming amphiphiles has been developed, based on the use of spermidine, spermine, lysine, and cholic acid. A kinetic analysis of Na+ transport across bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine by three dendritic amphiphiles has provided the strongest evidence to date for a barrel stave structure.

Cholic Acid↗
PubMed2003

Selective association of cholesterol with long-chain phospholipids in liquid-ordered bilayers: support for the existence of lipid rafts.

Nearest-neighbor recognition experiments, which have been carried out under fluidizing and condensing conditions, using exchangeable dimers derived from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and cholesterol, have provided strong evidence that sterol-phospholipid recognition is limited to the liquid-ordered phase.

Cholesterol↗
PubMed2003

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.

Cholesterol↗
PubMed2003

The gluing of a Langmuir-Blodgett bilayer.

Poly(4-styrenesulfonate) has been used to ionically cross-link (glue together) a single Langmuir-Blodgett bilayer derived from an amphiphilic calix[6]arene bearing six hexadecyl and six methylene-trimethylammonium groups. The resulting film is of high quality and robustness, as judged by its He/N2 permeation selectivity and by its ability to withstand exposure to chloroform solvent. The creation of a stable organic membrane, having a thickness that is less than 6 nm and a He/N2 permeation selectivity of ca. 305, represents a milestone for LB technology.

Journal Article↗
PubMed2003

Selective transport of ATP across a phospholipid bilayer by a molecular umbrella.

Acylation of each primary group of spermidine with cholic acid, followed by acylation of the secondary amino group using an activated form of Nalpha,Ndelta,Nomega-tri-CBZ-l-arginine, and subsequent hydrogenolysis, afforded a conjugate (i.e., 1) which readily transports adenosine 5-triphosphate, but not glutathione, across phospholipid bilayers made from 1-palmitoyl-2-oleyol-sn-glycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol.

Adenosine Triphosphate↗
PubMed2002

An ion conductor that recognizes osmotically-stressed phospholipid bilayers.

A synthetic ion conductor (1), derived from cholic acid and spermine, has been found capable of recognizing osmotic stress in liposomes made from 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine [(C16:1)PC]. Thus, when large unilamellar vesicles of (C16:1)PC are placed under hypotonic conditions, the Na+/Li+ transport activity of 1 increases by as much as 1 order of magnitude, relative to isotonic conditions

Antiporters↗
PubMed2002

A polymerized calix[6]arene monolayer having gas permeation selectivity that exceeds Knudsen diffusion.

A polymerized monolayer of 5,11,17,23,29,35-hexamercaptomethyl-37,38,40,41,42-hexakis-(1-n hexadecyloxy)calix[6]arene (1) has been synthesized on the surface of an ca. 15 mum-thick film derived from poly[1-(trimethylsilyl)-1-propyne] (PTMSP). This monolayer exhibits a permeation selectivity toward He and SF6 that exceeds Knudsen diffusion. Analogous membranes made from a calix[6]arene that contains amidoxime headgroups (i.e., 2) showed Knudsen diffusion characteristics.

Journal Article↗
PubMed2002

Selective sterol-phospholipid associations in fluid bilayers.

The nearest-neighbor preferences of three exchangeable lipid monomers (two phospholipids that differ in length, A and B, and a derivative of cholesterol, C) have been quantified in the fluid bilayer state by use of the nearest-neighbor recognition method (Davidson, S. K. M.; Regen, S. L. Chem. Rev. 1997, 97, 1269). Thus, an analysis of the equilibrium dimer distributions has shown that (i) the sterol favors both phospholipids as nearest neighbors relative to other sterol molecules, (ii) that this recognition is selective (i.e., the sterol favors the longer phospholipid as a nearest neighbor over the shorter one, especially when the sterol concentrations in the bilayer is high (e.g., 40 mol %), and (iii) the phospholipids, themselves, are unable to recognize each other. Taken together, these findings indicate that the probable mechanism by which cholesterol induces homoassociation of A and B in analogous bilayers is one in which the sterol "pulls" two or more of the longer phospholipid monomers (B) out of a "sea" of randomly mixed A and B. These findings also lend support for the notion of cholesterol-phospholipid complexation in fluid bilayers. The biological implications of these findings are briefly discussed.

Cholesterol↗
PubMed2002

Lipid-lipid recognition in fluid bilayers: solving the cholesterol mystery.

Nearest-neighbour recognition measurements take 'molecular-level snapshots' of lipid organization in fluid bilayers by detecting and quantifying the thermodynamic tendency of two lipids to become nearest-neighbours. Recent nearest-neighbour recognition experiments have clarified the structural role that cholesterol plays in biological membranes. They have also clarified the influence that the linkage region of sphingolipids, the sugar head group of glycolipids, and lipid-peptide interactions have on lipid-lipid recognition.

Cholesterol↗
PubMedDate not supplied

Molecular umbrella-assisted transport of thiolated AMP and ATP across phospholipid bilayers.

Two molecular umbrella-nucleoside conjugates (1a and 1b) have been synthesized via thiolate-disulfide displacement by adenosine 5'-O-(3-thiomonophosphate) and adenosine 5'-O-(3-thiotriphosphate) on an activated dimer derived from cholic acid, spermidine, and 5,5'-dithiobis-(2-nitrobenzoic acid). Both conjugates readily enter the aqueous compartment of liposomes made from 1-palmitoyl-2-oleyol-sn-glycero-3-phosphocholine (POPC) and release the free nucleoside upon reaction with entrapped glutathione. Approximately 50% of the thiolated form of AMP is released within 20 min at 23 degrees C; 120 min is required for a similar release of the thiolated form of ATP. The facile cleavage of these conjugates by glutathione, together with the fact that mammalian cells contain millimolar concentrations of this tripeptide in their cytoplasm, suggest that such chemistry may be extended to the practical development of prodrugs, e.g., antisense oligonucleotides that can be delivered into cells.

Adenosine Monophosphate↗
PubMedDate not supplied

Ion conductors derived from biogenic amines, bile acids, and amino acids.

A family of conjugates has been synthesized from spermine, putrescine, lysine, gamma-aminobutyric acid, sarcosine, cholic acid, glycocholic acid, 3alpha,7alpha-dihydroxycholic acid, and 3alpha,12alpha-dihydroxycholic acid, based on a design principle previously reported (Bandyopadhyay, P., Janout, V., Zhang, L., Regen, S. L. (2001) J. Am. Chem. Soc. 123, 7691). Each of these conjugates was found to exhibit significant activity in promoting the transport of Na(+) across liposomal membranes derived from 1,2-dimyristoleoyl-sn-glycero-3-phosphocholine, and also from 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine. In all cases, plots of pseudo first-order rate constants, k(obsd) vs (mol % of ion conductor)(2) were found to be linear, indicating that transport-active dimers are involved and that only a small fraction of the conjugates are in an aggregated form. An operational comparison that has been made within this series of conjugates indicates that Na(+) transport activity and membrane selectivity have a moderate dependency on the composition and the structure of the ion conductor.

Amino Acids↗
PubMedDate not supplied

Enhanced hydrolytic stability and water solubility of an aromatic nitrogen mustard by conjugation with molecular umbrellas.

Chlorambucil, an aromatic nitrogen mustard, has been conjugated to putrescine- and spermidine-based scaffolds bearing one, two, and four persulfated cholic acid units. Those conjugates bearing two or four sterols show improved hydrolytic stability and water solubility relative to chlorambucil. A similar conjugate that contained only one sterol unit shows negligible improvement in hydrolytic stability but a significant increase in water solubility. Qualitatively, the hydrolytic stability within this series of conjugates parallels the shielding effects that have previously been found for related conjugates bearing a pendant, hydrophobic fluorescent probe. In vitro studies indicate that these conjugates possess modest to moderate activity against certain human lymphoblastic leukemia and human colon carcinoma cells.

Cell Line, Tumor↗
PubMedDate not supplied

Fully detachable molecular umbrellas as peptide delivery agents.

A persulfated molecular umbrella, derived from cholic acid and spermidine, has been covalently attached to H-Tyr-D-Ala-Gly-Phe-D-Leu-OH (DADLE) by use of an o-dithiobenzyl carbamate linkage. Treatment of the resulting conjugate (1) with glutathione in solution resulted in the liberation of the free form of the peptide. Addition of 1 to glutathione-entrapped liposomes, prepared from 1-palmitoyl-2-oleyol-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG), and cholesterol [POPC/POPG/cholesterol, 72/4/24 (mol/mol/mol)], resulted in the delivery of DADLE into their aqueous interior.

Amino Acids↗