27 research outputs found
Development of a CP 31P NMR Broadline Simulation Methodology for Studying the Interactions of Antihypertensive AT1 Antagonist Losartan with Phospholipid Bilayers
A cross-polarization (CP) 31P NMR broadline simulation methodology was developed for studying the effects of
drugs in phospholipids bilayers. Based on seven-parameter fittings, this methodology provided information concerning the
conformational changes and dynamics effects of losartan in the polar region of the dipalmitoylphosphatidylcholine bilayers.
The test molecule for this study was losartan, an antihypertensive drug known to exert its effect on AT1 transmembrane receptors. The results were complemented and compared with those of differential scanning calorimetry, solid-state 13C NMR
spectroscopy, Raman spectroscopy, and electron spin resonance. More specifically, these physical chemical methodologies
indicated that the amphipathic losartan molecule interacts with the hydrophilic-head zone of the lipid bilayers. The CP 31P NMR
broadline simulations showed that the lipid molecules in the bilayers containing losartan displayed greater collective tilt compared
to the tilt displayed by the load-free bilayers, indicating improved packing. The Raman results displayed a decrease in the trans/
gauche ratio and increased intermolecular interactions of the acyl chains in the liquid crystalline phase. Additional evidence, suggesting that losartan possibly anchors in the realm of the headgroup, was derived from upfield shift of the average chemical shift
s
iso of the 31P signal in the presence of losartan and from shift of the observed peak at 715 cmÿ1
attributed to C-N stretching in the
Raman spectra
Recommended from our members
Comparative Clinical Outcomes and Patterns of Failure of Proton-Beam Therapy (PBT) versus Intensity-Modulated Radiotherapy (IMRT) for Prostate Cancer in the Postoperative Setting
Comparative biophysical studies of sartan class drug molecules losartan and candesartan (CV-11974) with membrane bilayers
Validating a Local Failure Risk Stratification for Use in Prospective Studies of Adjuvant Radiation Therapy for Bladder Cancer
Magnetic Levitation To Characterize the Kinetics of Free-Radical Polymerization
This
work describes the development of magnetic levitation (MagLev)
to characterize the kinetics of free-radical polymerization of water-insoluble,
low-molecular-weight monomers that show a large change in density
upon polymerization. Maglev measures density, and certain classes
of monomers show a large change in density when monomers covalently
join in polymer chains. MagLev characterized both the thermal polymerization
of methacrylate-based monomers and the photopolymerization of methyl
methacrylate and made it possible to determine the orders of reaction
and the Arrhenius activation energy of polymerization. MagLev also
made it possible to monitor polymerization in the presence of solids
(aramid fibers, and carbon fibers, and glass fibers). MagLev offers
a new analytical technique to materials and polymer scientists that
complements other methods (even those based on density, such as dilatometry),
and will be useful in investigating polymerizations, evaluating inhibition
of polymerizations, and studying polymerization in the presence of
included solid materials (e.g., for composite materials)