The Experts below are selected from a list of 63 Experts worldwide ranked by ideXlab platform
David Ronis - One of the best experts on this subject based on the ideXlab platform.
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Statistical mechanics of ionomeric colloids. II: Ionomer Conformational equilibria
Macromolecules, 1993Co-Authors: David RonisAbstract:Conformational equilibria in the charged region of spherical ionomeric colloids are studied using a self-consistent mean-field Monte Carlo method. It is shown that the ionomers do not adopt a single Type of Conformation but instead exhibit both rodlike and swollen coillike regions. The extent of these regions can be controlled by varying the screening length, curvature of the colloid core, and aggregation number
Jorge Morgado - One of the best experts on this subject based on the ideXlab platform.
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sparse coding denoising applied to reversible Conformational switching of a porphyrin self assembled monolayer induced by scanning tunnelling microscopy
Journal of Microscopy, 2018Co-Authors: Joao A B P Oliveira, Ana M Braganca, L Alcacer, Jorge Morgado, Mario A T Figueiredo, Jose M Bioucasdias, Quirina FerreiraAbstract:Scanning tunnelling microscopy (STM) was used to induce Conformational molecular switching on a self-assembled monolayer of zinc-octaethylporphyrin on a graphite/tetradecane interface at room temperature. A reversible Conformational change controlled by applying a tip voltage was observed. Consecutive STM images acquired at alternating tip voltages showed that at 0.4 V the porphyrin monolayer presents a molecular arrangement formed by alternate rows with two different Types of structural Conformations and when the potential is increased to 0.7 V the monolayer presents only one Type of Conformation. In this paper, we characterize these porphyrin Conformational dynamics by analyzing the STM images, which were improved for better quality and interpretation by means of a denoising algorithm, adapted to process STM images from state of the art image processing and analysis methods. STM remains the best technique to 'see' and to manipulate the matter at atomic scale. A very sharp tip a few angstroms of the surface can provide images of molecules and atoms with a powerful resolution. However, these images are strongly affected by noise which is necessary to correct and eliminate. This paper is about new computational tools specifically developed to denoise the images acquired with STM. The new algorithms were tested in STM images, obtained at room temperature, of porphyrin monolayer which presents reversible Conformational change in function of the tip bias voltage. Images with high resolution, acquired in real time, show that the porphyrins have different molecular arrangements whether the tip voltage is 0.4 V or 0.7 V.
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kinetics and thermodynamics of poly 9 9 dioctylfluorene β phase formation in dilute solution
Macromolecules, 2006Co-Authors: Fernando B Dias, Jorge Morgado, Antonio L Macanita, Fernando Pestana Da Costa, Hugh D Burrows, A P MonkmanAbstract:Poly(9,9-dioctylfluorene) (PFO) adopts a particular Type of Conformation in dilute solutions of the poor solvent methylcyclohexane (MCH) below 273 K, which is revealed by the appearance of a red-shifted absorption peak at 437-438 nm. The formation of this ordered Conformation depends on the temperature but is independent of polymer concentration over the range studied (3-25 Ig/mL). On the basis of absorption, steady- state, and time-resolved fluorescence data, the new absorption peak at 437-438 nm is assigned to a highly ordered Conformation of PFO chains, analogous to the so-called ‚-phase first identified in PFO films. From the study of PFO solutions in MCH as a function of temperature, we conclude that these ordered segments (‚-Conformation) coexist with less ordered domains in the same chain. When the ordered domains are present, they act as efficient energy traps and the fluorescence from the disordered regions is quenched. The transition between the disordered and the ordered PFO Conformations is adequately described by a mechanism that involves two steps: a first, essentially intramolecular, one from a relatively disordered ( R) to an ordered Conformation (‚), followed by aggregation of chains containing ‚-Conformation into anisotropic ordered domains. From the temperature dependence of the 437-438 nm peak intensity, the transition temperature T‚ ) 261 K, enthalpy ¢H‚ )- 18.0 kcal mol-1, and entropy ¢S‚ )- 68.4 cal K-1 mol-1 were obtained. The formation of the ‚-Conformation domains were also followed as a function of time at 260 K. The rate constants at 260 K were determined, showing an order of magnitude around 10-3 s-1 (kRf‚ ) 5.9 10-4 s-1; k‚fR ) 9 10-4 s-1; kagg ) 2.3 10-3 M-1 s-1; kdiss ) 4.4 10-4 s-1). This small magnitude explains the long times required for a "complete" conversion to the ‚-Conformation.
Anne S. Ulrich - One of the best experts on this subject based on the ideXlab platform.
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Antimicrobial and cell-penetrating peptides induce lipid vesicle fusion by folding and aggregation
European Biophysics Journal, 2012Co-Authors: Parvesh Wadhwani, Johannes Reichert, Jochen Bürck, Anne S. UlrichAbstract:According to their distinct biological functions, membrane-active peptides are generally classified as antimicrobial (AMP), cell-penetrating (CPP), or fusion peptides (FP). The former two classes are known to have some structural and physicochemical similarities, but fusogenic peptides tend to have rather different features and sequences. Nevertheless, we found that many CPPs and some AMPs exhibit a pronounced fusogenic activity, as measured by a lipid mixing assay with vesicles composed of typical eukaryotic lipids. Compared to the HIV fusion peptide (FP23) as a representative standard, all designer-made peptides showed much higher lipid-mixing activities (MSI-103, MAP, transportan, penetratin, Pep1). Native sequences, on the other hand, were less fusogenic (magainin 2, PGLa, gramicidin S), and pre-aggregated ones were inactive (alamethicin, SAP). The peptide structures were characterized by circular dichroism before and after interacting with the lipid vesicles. A striking correlation between the extent of Conformational change and the respective fusion activities was found for the series of peptides investigated here. At the same time, the CD data show that lipid mixing can be triggered by any Type of Conformation acquired upon binding, whether α-helical, β-stranded, or other. These observations suggest that lipid vesicle fusion can simply be driven by the energy released upon membrane binding, peptide folding, and possibly further aggregation. This comparative study of AMPs, CPPs, and FPs emphasizes the multifunctional aspects of membrane-active peptides, and it suggests that the origin of a peptide (native sequence or designer-made) may be more relevant to define its functional range than any given name.
A P Monkman - One of the best experts on this subject based on the ideXlab platform.
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kinetics and thermodynamics of poly 9 9 dioctylfluorene β phase formation in dilute solution
Macromolecules, 2006Co-Authors: Fernando B Dias, Jorge Morgado, Antonio L Macanita, Fernando Pestana Da Costa, Hugh D Burrows, A P MonkmanAbstract:Poly(9,9-dioctylfluorene) (PFO) adopts a particular Type of Conformation in dilute solutions of the poor solvent methylcyclohexane (MCH) below 273 K, which is revealed by the appearance of a red-shifted absorption peak at 437-438 nm. The formation of this ordered Conformation depends on the temperature but is independent of polymer concentration over the range studied (3-25 Ig/mL). On the basis of absorption, steady- state, and time-resolved fluorescence data, the new absorption peak at 437-438 nm is assigned to a highly ordered Conformation of PFO chains, analogous to the so-called ‚-phase first identified in PFO films. From the study of PFO solutions in MCH as a function of temperature, we conclude that these ordered segments (‚-Conformation) coexist with less ordered domains in the same chain. When the ordered domains are present, they act as efficient energy traps and the fluorescence from the disordered regions is quenched. The transition between the disordered and the ordered PFO Conformations is adequately described by a mechanism that involves two steps: a first, essentially intramolecular, one from a relatively disordered ( R) to an ordered Conformation (‚), followed by aggregation of chains containing ‚-Conformation into anisotropic ordered domains. From the temperature dependence of the 437-438 nm peak intensity, the transition temperature T‚ ) 261 K, enthalpy ¢H‚ )- 18.0 kcal mol-1, and entropy ¢S‚ )- 68.4 cal K-1 mol-1 were obtained. The formation of the ‚-Conformation domains were also followed as a function of time at 260 K. The rate constants at 260 K were determined, showing an order of magnitude around 10-3 s-1 (kRf‚ ) 5.9 10-4 s-1; k‚fR ) 9 10-4 s-1; kagg ) 2.3 10-3 M-1 s-1; kdiss ) 4.4 10-4 s-1). This small magnitude explains the long times required for a "complete" conversion to the ‚-Conformation.
Hiroyuki Higashiyama - One of the best experts on this subject based on the ideXlab platform.
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In Vitro and In Silico Characterization of Lemborexant (E2006), a Novel Dual Orexin Receptor Antagonist
Journal of Pharmacology and Experimental Therapeutics, 2017Co-Authors: Carsten T. Beuckmann, Michiyuki Suzuki, Kazuya Nagaoka, Tohru Arai, Takashi Ueno, Hiroyuki HigashiyamaAbstract:Orexin (hypocretin) neuropeptides have, among others, been implicated in arousal/sleep control, and antagonizing the orexin signaling pathway has been previously demonstrated to promote sleep in animals and humans. This mechanism opens up a new therapeutic approach to curb excessive wakefulness in insomnia disorder rather than to promote sleep-related signaling. Here we describe the preclinical pharmacological in vitro and in silico characterization of lemborexant ((1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide)), a dual orexin receptor antagonist (DORA), as a novel experimental therapeutic agent for the symptomatic treatment of insomnia disorder and compare its properties to two other DORAs, almorexant and suvorexant. Lemborexant binds to both orexin receptors and functionally inhibits them in a competitive manner with low nanomolar potency, without any species difference apparent among human, rat, and mouse receptors. Binding and dissociation kinetics on both orexin receptors are rapid. Lemborexant is selective for both orexin receptors over 88 other receptors, transporters, and ion channels of important physiologic function. In silico modeling of lemborexant into the orexin receptors showed that it assumes the same Type of Conformation within the receptor-binding pocket as suvorexant, the π-stacked horseshoe-like Conformation.
