Network


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

Hotspot


Dive into the research topics where Vaclav Janout is active.

Publication


Featured researches published by Vaclav Janout.


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.


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 | 2010

Glued Langmuir-Blodgett bilayers from calix[n]arenes: Influence of calix[n]arene size on ionic cross-linking, film thickness, and permeation selectivity

Minghui Wang; Vaclav Janout; Steven L. Regen

A homologous series of calix[4]arene-, calix[5]arene-, and calix[6]arene-based surfactants, containing pendant trimethylammonium and n-hexadecyl groups, have been compared with respect to their ability (i) to undergo ionic cross-linking at the air/water interface, (ii) to incorporate poly(4-styrenesulfonate) (PSS) in Langmuir-Blodgett (LB) bilayers, and (iii) to act as barriers toward He, N(2), and CO(2) when assembled into cross-linked LB bilayers. As these calix[n]arenes increase in size, their ability to undergo ionic cross-linking has been found to increase, the thickness of corresponding glued LB bilayers has been found to decrease, and their barrier properties and permeation selectivities have been found to increase. The likely origin for these effects and the probable mechanism by which He, N(2), and CO(2) cross these ultrathin films are discussed.


Bioconjugate Chemistry | 2014

Molecular Umbrella Conjugate for the Ocular Delivery of siRNA

Vaclav Janout; Lauren L. Cline; Bradley P. Feuston; Lee Klein; A. C. O’Brien; Tom Tucker; Yu Yuan; Lynn A. O’Neill-Davis; Robert Louis Peiffer; Sandhya S. Nerurkar; Vasant Jadhav; David M. Tellers; Steven L. Regen

The synthesis, computer modeling, and biological activity of an octawalled molecular umbrella short interfacing RNA (siRNA) conjugate is described. This molecular umbrella–siRNA conjugate exhibited mRNA knockdown activity in vitro in the absence of a transfection reagent. Evaluation of this molecular umbrella conjugate in vivo, using the rat eye via intravitreal injection, resulted in sequence specific mRNA knockdown in the retina with no obvious signs of toxicity, as judged by ophthalmic examination.


Bioconjugate Chemistry | 2011

A molecular umbrella approach to the intracellular delivery of small interfering RNA.

Lauren L. Cline; Vaclav Janout; Michael Fisher; Rudolph L. Juliano; Steven L. Regen

A series of diwalled and tetrawalled molecular umbrellas have been synthesized using cholic acid, spermidine, and lysine as starting materials. Coupling of these molecular umbrellas to an octaarginine peptide afforded agents that were capable of promoting the transport of small interfering RNA to HeLa cells, as judged by the knockdown of enhanced green fluorescent protein expression. The efficiency of this knockdown was found to increase with an increasing number of facially amphiphilic walls present, and also when a cleavable disulfide linker was replaced with a noncleavable, maleimido moiety; i.e., a group that is not susceptible to thiolate-disulfide interchange. The knockdown efficiency that was observed for one tetrawalled molecular umbrella-octaargine conjugate was comparable to that observed with a commercially available transfection agent, Lipofectamine 2000, but the conjugate showed less cytotoxicity.


Bioconjugate Chemistry | 2008

Cellular entry and nuclear targeting by a highly anionic molecular umbrella.

Mohamed Mehiri; Bingwen Jing; Danielle N. Ringhoff; Vaclav Janout; Lynne Cassimeris; Steven L. Regen

A fluorescently labeled, persulfated molecular umbrella ( 1) has been synthesized from cholic acid, lysine, spermine, and Coumarin 343 and found capable of entering live HeLa cells. The distributions of 1 throughout the cytoplasm and the nucleus were diffuse and punctate, respectively. This finding, together with its ability to cross liposomal membranes by passive diffusion, suggests that passive diffusion plays a significant role in the ability of 1 to enter cells. The fact that 1 is concentrated at the nucleus raises the possibility that molecular umbrellas of this type could be used for the nuclear targeting of drugs.


Bioconjugate Chemistry | 2014

Molecular Umbrella–Amphotericin B Conjugates

Vaclav Janout; Celine Bienvenu; Wiley A. Schell; John R. Perfect; Steven L. Regen

A tetrawalled and an octawalled molecular umbrella conjugate of amphotericin B (AmB) have been synthesized. Both conjugates exhibit high water solubility, a low tendency to aggregate, negligible hemolytic activity at 100 μM, and an ability to release a derivative of AmB under reducing conditions that exhibits high antifungal activity. Whereas the larger, octawalled conjugate shows slight adsorption to liposomal membranes and an ability to cross them by passive transport, the tetrawalled analogue shows significant adsorption and much lower bilayer transport activity. The potential of molecular umbrella–AmB conjugates as therapeutic agents is briefly discussed.


Tetrahedron Letters | 1999

N-[O-1,2,3-benzotriazin-4(3H)one-yl]-3,(2-pyridyldithio)propionate: A more reactive alternative to SPDP☆

Vaclav Janout; Marion Lanier; Steven L. Regen

Abstract N-[O-1,2,3-Benzotriazin-4(3H)one-yl]-3-(2-pyridyldithio)propionate [BPDP] has been synthesized and found to react with secondary amines to give high yields of acylated product. In sharp contrast, the widely used heterobifunctional coupling reagent, N-[O-succinimdy]-3-(2-pyridyldithio) propionate [SPDP] afforded low to negligible yields of product.


Bioconjugate Chemistry | 2012

Stimulated release of cholesterol from liposomal membranes by a PEGylated phospholipid.

Vaclav Janout; Trevor A. Daly; Lauren L. Cline; Leah J. Kulp; Steven L. Regen

PEGylated phospholipids are commonly used to increase the blood-circulation time of liposomes by providing a steric barrier around them. This paper documents a fundamentally new property of these lipids-an ability to stimulate the release of cholesterol from phospholipid membranes. Evidence for such stimulation has been obtained by measuring the transport of dehydroergosterol (DHE), a fluorescent simulant of cholesterol, from donor liposomes made from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG(2000)), and DHE to acceptor liposomes made from POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), and cholesterol. The potential of PEGylated lipids to serve as novel cholesterol-lowering agents is briefly discussed.


Bioconjugate Chemistry | 2015

Correction to Molecular Umbrella-Amphotericin B Conjugates.

Vaclav Janout; Celine Bienvenu; Wiley A. Schell; John R. Perfect; Steven L. Regen

A ll sterols that appear on the right side of each molecular umbrella framework shown in the Abstract, Text, and Table of Contents should have been drawn with the natural stereochemistry of cholic acid shown below and not that of its enantiomer: This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

Collaboration


Dive into the Vaclav Janout's collaboration.

Top Co-Authors

Avatar

Steven L. Regen

Icahn School of Medicine at Mount Sinai

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge