Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Steven L. Regen is active.

Publication


Featured researches published by Steven L. Regen.


Journal of the American Chemical Society | 1986

Polymer-encased vesicles derived from dioctadecyldimethylammonium methacrylate

Hiroyuki Fukuda; Tadeusz. Diem; James. Stefely; Ferenc J. Kezdy; Steven L. Regen

Dispersal of dioctadecyldimethylammonium methacrylate (DODAM) in water via ultrasonic irradiation yielded small-diameter vesicles having a phase transition at ca. 42-46/sup 0/C. Photopolymerization (254 nm) at 30 and 60/sup 0/C resulted in the formation of polymer-encased vesicles which retained phase-transition behavior. Combination of dynamic light scattering, electron microscopy, and captured volume data provides strong evidence for vesicle shrinkage when polymerization is carried out at 60/sup 0/C; shrinkage occurring during photopolymerization at 30/sup 0/C is less certain. Poly(methacrylic acid), derived from 30/sup 0/-polymerized vesicles (30/sup 0/-polymerized means polymerized at 30/sup 0/C in this paper), was 75.4% syndiotactic, 22.3% heterotactic, and 2.3% isotactic and was significantly more soluble in DMF than poly(methacrylic acid) derived from 60/sup 0/-polymerized vesicles; the latter polymer was predominantly syndiotactic. At 25/sup 0/C, nonpolymerized, 30/sup 0/-polymerized, and 60/sup 0/-polymerized vesicles showed similar permeability toward sucrose; at 60/sub 0/C, the 60/sup 0/-polymerized vesicles were less permeable. Storage of the 60/sup 0/-polymerized and the nonpolymerized DODAM vesicles for 2 months at room temperature revealed the former to be more stable. The monolayer properties and photopolymerization behavior of DODAM have been investigated at the air-water interface.


Journal of Virology | 2007

Molecular Umbrellas: a Novel Class of Candidate Topical Microbicides To Prevent Human Immunodeficiency Virus and Herpes Simplex Virus Infections

Rebecca Pellett Madan; Pedro M. M. Mesquita; Natalia Cheshenko; Bingwen Jing; Vikas Shende; Esmeralda Guzman; Taylor Heald; Marla J. Keller; Steven L. Regen; Robin J. Shattock; Betsy C. Herold

ABSTRACT Molecular umbrella compounds may function as novel topical microbicides to prevent human immunodeficiency virus (HIV) and herpes simplex virus (HSV) infections. In a preliminary structure-activity investigation, one umbrella compound, designated Spm8CHAS, was identified which inhibited both HIV and HSV infections with no cellular toxicity. The objectives of the current studies were to define its spectrum of antiviral activity, characterize its mechanism of action, and explore the possibility of combining Spm8CHAS with HIV-specific reverse transcriptase inhibitors. Spm8CHAS inhibited infections by laboratory and clinical R5 and X4 clade B and clade C HIV strains in cell culture. Ectocervical tissue explants exposed to HIV-1BaL in the presence of Spm8CHAS were completely protected (50% inhibitory concentration [IC50], 13.6 μg/ml), and transfer of virus to target T cells via migratory cells was abolished (IC50, 3.8 μg/ml). Spm8CHAS inhibited HSV-2 infection of epithelial cells 10,000-fold if present throughout the infection. Notably, adding Spm8CHAS to cultures following HSV entry significantly reduced viral infection, indicating that the drug also acts postentry. Subsequent studies indicated that Spm8CHAS blocks cell-to-cell spread of HSV. Confocal microscopy using a fluorescently labeled analog of Spm8CHAS demonstrated that this conjugate crosses the plasma cell membrane and is transported to the nucleus. Combinations of Spm8CHAS with UC-781 or 9-[R-2-(phosphonylmethoxy)propyl] adenine monohydrate in vitro exhibited additive anti-HIV activity with preserved anti-HSV activity. The abilities of Spm8CHAS to inhibit primary isolates of HIV, block HSV infection postentry, and cross cell membranes support the development of a combination microbicide containing Spm8CHAS with an HIV-specific reverse transcriptase inhibitor to prevent both HIV and HSV infections by multiple mechanisms.


Journal of the American Chemical Society | 2009

Loosening and Reorganization of Fluid Phospholipid Bilayers by Chloroform

Serhan Turkyilmaz; Wen-Hua Chen; Hideyuki Mitomo; Steven L. Regen

The mixing behavior of an exchangeable phospholipid (A) with an exchangeable sterol (B) in host bilayers made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) containing varying concentrations of cholesterol has been examined via the nearest-neighbor recognition method. At low sterol concentrations (i.e., 2.5 mol %), the mixing between A and B is close to ideal. Incremental increases in the sterol concentration to 40 mol % led to net increases in the affinity between A and B. Similar mixing experiments that were carried out in the presence of chloroform showed a leveling effect, where moderate sterol-phospholipid affinity was observed in all cases. These results, together with the fact that the number of chloroform molecules that are absorbed per phospholipid is essentially constant and independent of the sterol content, support a model in which chloroform favors solvation of the phospholipids and a common membrane state is produced. Fluorescence measurements and Raman spectra have also shown that chloroform significantly loosens both cholesterol-poor and cholesterol-rich membranes made from DPPC. In a broader context, these results suggest a fundamentally new mechanism of anesthesia, where the anesthetic, by solvating the lipid components, profoundly changes the lateral organization of the lipid framework.


Journal of the American Chemical Society | 2008

Defects in a Polyelectrolyte Multilayer: The Inside Story

Yao Wang; Erwin R. Stedronsky; Steven L. Regen

Moderate changes in the concentration of poly(sodium 4-styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) used in fabricating polyelectrolyte multilayers (PEMs) have been found to strongly affect the formation of defects (i.e., gaps) within these films, as revealed by gas permeation selectivity measurements. Thus, PEMs made from 14 alternating layers of PSS and PAH under “high” concentration conditions (15.0 mM in repeat units) exhibit He/N2 permeation selectivities that are greater than 200. In sharp contrast, analogous films of similar thickness that are made from 24 alternating layers of PSS and PAH under “low” concentration conditions (1.0 mM in repeat units) showed no significant He/N2 permeation selectivity, reflecting the presence of defects. Analogous PEMs that were fabricated from 14 alternating layers of PSS and PAH, using 1.0 mM PSS and PAH in the presence of added NaCl, where reduced viscosities and polymer conformations were matched with those found under high concentration con...


Journal of the American Chemical Society | 2015

Push and pull forces in lipid raft formation: the push can be as important as the pull.

Chang Wang; Martin R. Krause; Steven L. Regen

Nearest-neighbor recognition measurements have been made using exchangeable mimics of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine in the liquid-ordered (lo) and liquid-disordered (ld) states. In the ld phase, the net interaction between these two lipids is repulsive. In the lo phase, their interactions are neither attractive nor repulsive. These results, together with previous nearest-neighbor measurements, imply that the overall driving force for lipid domain formation in bilayers composed of high-melting lipids, low-melting lipids, and cholesterol, corresponds to a strong pull (attraction) between the high-melting lipids and cholesterol, a significant push (repulsion) between the low-melting and high-melting lipids, and a significant push between the low-melting lipids and cholesterol. In a broader context, these results provide strong support for the notion that repulsive forces play a major role in the formation of lipid rafts.


Bioconjugate Chemistry | 2009

A fine line between molecular umbrella transport and ionophoric activity.

Wen-Hua Chen; Vaclav Janout; Masaharu Kondo; Arevik Mosoian; Goar Mosoyan; Ravil R. Petrov; Mary E. Klotman; Steven L. Regen

A persulfated molecular umbrella derived from one spermine, four lysine, and eight deoxycholic acid molecules was found to exhibit ionophoric activity, as shown by pH discharge and Na(+) and Cl(-) transport experiments. In sharp contrast, a moderately more hydrophilic analogue derived from cholic acid showed no such ionophoric activity. Both molecular umbrellas crossed liposomal membranes by passive transport with experimental rates that were similar. These findings show how the interactions between such amphomorphic molecules and phospholipid bilayers are a sensitive function of the umbrellas hydrophilic/lipophilic balance (HLB). They also raise the possibility of exploiting molecular umbrellas in fundamentally new ways.


Journal of the American Chemical Society | 2008

Viewing Membrane-Bound Molecular Umbrellas By Parallax Analyses

Masaharu Kondo; Mohamed Mehiri; Steven L. Regen

Fluorescence quenching measurements have been made for a series of di-walled and tetra-walled molecular umbrellas having moderate (i.e., hydroxyl-) and strong (i.e., sulfate-) facial hydrophilicity, using Cascade Blue as the fluorophore. Through the use of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphotempocholine, 1-palmitoyl-2-stearoyl-(5-DOXYL)-sn-glycero-3-phosphocholine, and 1-palmitoyl-2-stearoyl-(12-DOXYL)-sn-glycero-3-phosphocholine as fluorescence quenchers, evidence has been obtained for a membrane-bound state in which the umbrella molecules lie on the surface of the lipid bilayer. In the case of the sulfated molecular umbrellas, evidence has also been obtained for a subpopulation in which the fluorophore lies deeper within the membrane. Probable structures for the shallow-lying and deep-lying molecular umbrellas are discussed.


Bioconjugate Chemistry | 2015

Taming Amphotericin B

Vaclav Janout; Wiley A. Schell; Damien Thévenin; Yuming Yu; John R. Perfect; Steven L. Regen

A strategy is introduced for enhancing the cellular selectivity of Amphotericin B (AmB) and other classes of membrane-disrupting agents. This strategy involves attaching the agent to a molecular umbrella to minimize the disruptive power of aggregated forms. Based on this approach, AmB has been coupled to a molecular umbrella derived from one spermidine and two cholic acid molecules and found to have antifungal activities approaching that of the native drug. However, in sharp contrast to AmB, the hemolytic activity and the cytotoxcity of this conjugate toward HEK293 T cells have been dramatically reduced.


Langmuir | 2014

Polyelectrolyte Multilayers on PTMSP as Asymmetric Membranes for Gas Separations: Langmuir–Blodgett versus Self-Assembly Methods of Anchoring

Cen Lin; Qibin Chen; Song Yi; Minghui Wang; Steven L. Regen

Polyelectrolyte multilayers derived from poly(diallyldimethylamonium chloride) and poly(sodium 4-styrenesulfonate) have been deposited onto poly[1-(trimethylsilyl)-1-propyne] (PTMSP) with anchoring layers formed by Langmuir-Blodgett and self-assembly methods. Using gas permeation selectivity as a basis for judging the efficacy of each anchoring method, we have found that similar CO2/N2 selectivities (ranging from 110 to 140) could be achieved by both methods and that their permeances were also similar. Although LB anchors require fewer layers of polyelectrolyte to reach this level of selectivity, the greater ease associated with self-assembly and its applicability to curved, high-surface-area supports (e.g., PTMSP-coated hollow fibers) encourage its use with PTMSP in creating new membrane materials for the practical separation of gases.


Langmuir | 2014

Push-pull mechanism for lipid raft formation.

Martin R. Krause; Trevor A. Daly; Paulo F. Almeida; Steven L. Regen

A quantitative assessment has been made of the interaction between exchangeable mimics of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol in the liquid-ordered (l0) and the liquid-disordered (ld) states using the nearest-neighbor recognition (NNR) method. This assessment has established that these lipids mix ideally in the l0 phase (i.e., they show no net attraction or repulsion toward each other) but exhibit repulsive interactions in the ld phase. The implications of these findings for the interactions between unsaturated phospholipids and cholesterol in eukaryotic cell membranes are briefly discussed.

Collaboration


Dive into the Steven L. Regen's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Alok Singh

United States Naval Research Laboratory

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge