Combinatorial
Chemistry & High Throughput Screening
ISSN: 1386-2073
Combinatorial Chemistry &
High Throughput Screening
Volume 14, Number 4, May 2011
Contents
Fabricating Gradient Hydrogel Scaffolds for 3D Cell
Culture Pp. 227-236
Kaushik Chatterjee, Marian F. Young and
Carl G. Simon Jr.
[Abstract] [Purchase
Article]
Procaine
Effect on Human Erythrocyte Membrane Explored by Atomic Force
Microscopy Pp. 237-247
Ulpiu Vlad Zdrenghea, Gheorghe Tomoaia, Daniela-Vasilica
Pop-Toader, Aurora Mocanu, Ossi Horovitz and Maria
Tomoaia-Cotisel
[Abstract] [Purchase
Article]
Two
Panels of Steroid Receptor Luciferase Reporter Cell Lines
for Compound Profiling Pp. 248-266
David Sedlák, Aileen Paguio and
Petr Bartůněk
[Abstract] [Full
Text Article]
Novel
Affinity Ligands for Chromatography Using Combinatorial Chemistry
Pp. 267-278
Tor Regberg, Charlotta Lindquist, Åke Pilotti,
Christel Ellström, Lars Fägerstam, Ann Eckersten,
Yasuro Shinohara, Steven L. Gallion and Joseph C.
Hogan Jr
[Abstract] [Purchase
Article]
Chemistry
Explained by Topology: An Alternative Approach Pp.
279-283
Jorge Galvez, Vincent M. Villar, María
Galvez-Llompart and José M. Amigó
[Abstract] [Purchase
Article]
Recent
Advances on Potentiometric Membrane Sensors for Pharmaceutical
Analysis Pp. 284-302
Vinod K. Gupta, Arunima Nayak, Shilpi Agarwal
and Barkha Singhal
[Abstract] [Purchase
Article]
Patent
Review Pp. 303-305
Anuradha Roy
Abstracts
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Article]
Fabricating Gradient Hydrogel Scaffolds for 3D
Cell Culture
Kaushik Chatterjee, Marian F. Young and
Carl G. Simon Jr.
Optimizing cell-material interactions is critical for
maximizing regeneration in tissue engineering. Combi-natorial
and high-throughput (CHT) methods can be used to systematically
screen tissue scaffolds to identify optimal biomaterial properties.
Previous CHT platforms in tissue engineering have involved
a two-dimensional (2D) cell culture format where cells were
cultured on material surfaces. However, these platforms are
inadequate to predict cellular response in a three-dimensional
(3D) tissue scaffold. We have developed a simple CHT platform
to screen cell-material interactions in 3D culture format
that can be applied to screen hydrogel scaffolds. Herein we
provide detailed instructions on a method to prepare gradients
in elastic modulus of photopolymerizable hydrogels.
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Procaine
Effect on Human Erythrocyte Membrane Explored by Atomic Force
Microscopy
Ulpiu Vlad Zdrenghea, Gheorghe Tomoaia, Daniela-Vasilica
Pop-Toader, Aurora Mocanu, Ossi Horovitz and Maria
Tomoaia-Cotisel
The procaine effect on human erythrocytes was investigated
by atomic force microscopy (AFM) at three procaine concentrations,
about
5 x 10-7
M, 5 x 10-5
M and 5 x 10-4 M.
The changes in surface morphology of erythrocyte membrane
bring direct evidence on the procaine effect on the cell membrane
at micro- and nanometer scale. AFM images of the control erythrocytes
(without procaine) showed a well defined concave (donut) shape
of cells. The structure of control erythrocytes membrane is
featured by closely packed nanometer size intra-membranous
particles. After the incubation of the fresh blood with increasing
procaine concentrations, a progressive increase in both concave
depth and surface roughness of erythrocyte membrane was observed.
The particles (granules) of the membrane surface increased
progressively with increasing procaine concentrations. The
changes in the surface morphology of erythrocyte membrane
can be associated with the enlargement of surface granules,
due to the aggregation of membranous particles within the
cell surface, and the domain structure formation induced by
procaine. A large number of moderate elevations from 25 nm
to almost 40 nm in lateral size were found to be rather uniformly
distributed on the surface of whole erythrocytes at low and
medium procaine concentrations, respectively. At the highest
procaine concentration, the granules of about 80 nm to almost
90 nm lateral size were found to form rows rather well separated.
These data are in substantial agreement with the published
results obtained on membrane models in the presence of procaine.
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[Full
Text Article]
Two
Panels of Steroid Receptor Luciferase Reporter Cell Lines
for Compound Profiling
David Sedlák, Aileen Paguio and
Petr Bartůněk
Steroid
hormone receptors represent a major target in drug discovery.
As ligand inducible transcription factors, their activity
can be modulated by small lipophilic molecules. Here we describe
two panels of potent and selective luciferase reporter cell
lines based on cells with low endogenous steroid receptor
activity (U2OS). The panels contain reporter cell lines for
estrogen receptors α
and β,
androgen, glucocorticoid, mineralocorticoid, and progesterone
receptors. In the first panel, the activation of either synthetic,
steroid response elements containing promoter or viral promoter
is mediated by full-length steroid receptors. The second panel
is based on the expression of the chimeric receptor, which
was created by the replacement of the N-terminal part of the
molecule by Gal4 DBD and that binds to multiple UAS sites
in the reporter promoter. Both panels were extensively characterized
by profiling 28 ligands in dose response manner in agonist
and antagonist mode. We have analyzed and compared the responses
to tested ligands from both panels and concluded that in general
both systems generated similar qualitative response in terms
of potency, efficacy, partial agonism/antagonism, mixed agonistic/antagonistic
profiles and the rank of potencies was well conserved between
both panels. However, we have also identified some artifacts
introduced by the Gal4/LBD reporter assays in contrast to
their full-length receptor reporter counterparts. Keeping
in mind the advantages and drawbacks of each reporter format,
these cell lines represent powerful and selective tools for
profiling large compound libraries (HTS) and for detailed
study of mechanisms by which compounds exert their biological
effects.
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to top]
[Purchase
Article]
Novel
Affinity Ligands for Chromatography Using Combinatorial Chemistry
Tor Regberg, Charlotta Lindquist, Åke Pilotti,
Christel Ellström, Lars Fägerstam, Ann Eckersten,
Yasuro Shinohara, Steven L. Gallion and Joseph C.
Hogan Jr
Spatially
addressable combinatorial libraries were synthesized by solution
phase chemistry and screened for binding to human serum albumin.
Members of arylidene diamide libraries were among the best
hits found, having submicromolar binding affinities. The results
were analyzed by the frequency with which particular substituents
appeared among the most potent compounds. After immobilization
of the ligands either through the oxazolone or the amine substituent,
characterization by surface plasmon resonance showed that
ibuprofen affected the binding kinetics, but phenylbutazone
did not. It is therefore likely that these compounds bind
to Site 2 in sub domain IIIA of human serum albumin (HSA).
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to top]
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Chemistry
Explained by Topology: An Alternative Approach
Jorge Galvez, Vincent M. Villar, María
Galvez-Llompart and José M. Amigó
Molecular topology can be considered an application of
graph theory in which the molecular structure is characterized
through a set of graph-theoretical descriptors called topological
indices. Molecular topology has found applications in many
different fields, particularly in biology, chemistry, and
pharmacology. The first topological index was introduced by
H. Wiener in 1947 [1]. Although its very first application
was the prediction of the boiling points of the alkanes, the
Wiener index has demonstrated since then a predictive capability
far beyond that. Along with the Wiener index, in this paper
we focus on a few pioneering topological indices, just to
illustrate the connection between physicochemical properties
and molecular connectivity.
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Article]
Recent
Advances on Potentiometric Membrane Sensors for Pharmaceutical
Analysis
Vinod K. Gupta, Arunima Nayak, Shilpi Agarwal
and Barkha Singhal
Prime concerns with modern developments are attributed
to high level undetected but important biological substances
or even toxicants cycled often among individual and populations;
which in turn agonizes environmental monitoring, trace-gas
detection, water treatment facilities, in vivo detection
in biological fluids and other accomplishments. For the detection
of such analytes, several analytical devices combined with
biological component have been designed with a physiochemical
detector component. Here, we essentially focus on drug-based
potentiometric membrane sensors known as ion selective electrodes
(ISEs). The functionality of ion-selective membrane is quite
intricate, challenging, and our undertsanding is yet to be
thrived with more interventions. ISEs have applied explications
to enormous variety of analytical inquires as well as informative
tools for probing host-guest chemistry. However, expansion
of ISEs based applications is aimed to improve the system
performance, acquiring enhanced understanding of their response
mechanism, and finding new chemical or physical configurations
mainly for human welfare. The major strength of ISEs is the
precised analytical information, assured by using the ion-selective
membrane electrodes used successfully for both in vitro
and in vivo assays of pharmaceutical products
as well as in clinical analyses. In this
review, we attempt to provide a brief prologue to the applicability
and advantages of potentiometric sensors in the analysis of
pharmaceutically active compounds emphasizing their employment
at molecular level for in situ selection of biologically
important analytes. |
