bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vibrational circular dichroism and IR spectral analysis as a test of theoretical conformational modeling for a cyclic hexapeptide
Authors: Bour Petr , Kim Joohyun , Kapitan Josef , Hammer Robert P. , Huang Rong , Wu Ling , Keiderling Timothy A. 
Published: May 2008

AbstractA model cyclohexapeptide, cyclo‐(Phe‐DPro‐Gly‐Arg‐Gly‐Asp) was synthesized and its IR and VCD spectra were used as a test of density functional theory (DFT) level predictions of spectral intensities for a peptide with a nonrepeating but partially constricted conformation. Peptide structure and flexibility was estimated by molecular dynamics (MD) simulations and the spectra were simulated using full quantum mechanical (QM) approaches for the complete peptide and for simplified models with truncated side chains. After simulated annealing, the backbone conformation of the ring structure is relatively stable, consisting of a normal β‐turn and a tight loop (no H‐bond) which does not vary over short trajectories. Only in quite long MD runs at high temperatures do other conformations appear. MD simulations were carried out for the cyclic peptide in water and in TFE, which match experimental solvents, as well as with and without protonation of the Asp carboxyl group. DFT spectral simulations were made using the annealed structure and were extended to include basis set variation, to determine an optimal computational approach, and solvent simulation with a polarized continuum model (PCM). Stepwise full DFT simulation of spectra was done for various sequences with the same backbone geometry but based on (1) solely Gly residues, (2) Ala substitution except Gly and Pro, and (3) complete sequences with side chains. Additionally, a selection of structures was used to compute IR and VCD spectra with the optimal method to determine structural variation effects. The side chains, especially the AspCOOH and ArgNH2 transitions, had an impact on the computed amide frequencies, IR intensities and VCD pattern. Since experimentally these groups would have little chirality, due to conformational variation, they do not impact the observed VCD spectra. Correcting for frequency shifts, the Ala model for the cyclopeptide gives the clearest representation of the amide VCD. The experimental sign pattern for the amide I' band in D2O and also the sharper, more intense amide I VCD band in TFE was seen to some degree in one conformer with Type II′ turns, but the data favor a mix of structures. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Use of large‐scale chromatography in the preparation of armodafinil
Authors: Hauck Willy , Adam Philippe , Bobier Christelle , Landmesser Nelson 
Published: May 2008

AbstractArmodafinil, the (R)‐enantiomer of modafinil, is a medication used to treat the excessive sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder. We report here the chemical development of armodafinil and the investigations that led to a commercial route to prepare this pure enantiomer. Three synthetic approaches were used to provide the chiral sulfoxide. Resolution via preferential crystallization was used for phase I clinical trials and was subsequently replaced by chiral chromatography, enabling us to pursue a rapid filing and registration of the API. Finally, the commercial route was developed and employed asymmetric oxidation catalyzed by a titanium(IV) isopropoxide and diethyl tartrate system. The advantages of choosing a chromatographic development pathway to expedite registration while concurrently developing an economical chiral synthesis route is discussed in the context of armodafinil development. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Chiral phosphites derived from carboranes: Electronic effect in catalytic asymmetric hydrogenation
Authors: Lyubimov Sergey E. , Kalinin Valery N. , Tyutyunov Andrey A. , Olshevskaya Valentina A. , Dutikova Yulia V. , Cheong Chan Seong , Petrovskii Pavel V. , Safronov Anton S. , Davankov Vadim A. 
Published: May 2008

AbstractA series of new fine‐tunable monodentate phosphite and phosphoramidite ligands based on carboranes have been synthesized and used for asymmetric Rh‐catalyzed hydrogenation of prochiral olefins with the result of up to 99.8% ee. Dependence of the enantioselectivity on the electron‐withdrawing or electron‐donating properties of the carboranyl substituent has been studied. Chirality, 2009. © 2008 Wiley‐Liss, Inc.
A new reference material for UV–visible circular dichroism spectroscopy
Authors: Damianoglou Angeliki , Crust Edward J. , Hicks Matthew R. , Howson Suzanne E. , Knight Alex E. , Ravi Jascindra , Scott Peter , Rodger Alison 
Published: May 2008

AbstractTo obtain accurate and consistent measurements from circular dichroism (CD) instruments over time and from different laboratories, it is important that they are properly calibrated. The characteristics of the available reference materials are not ideal to ensure proper calibration as they typically only give peaks in one or two spectral regions, and often have issues concerning purity and stability. Currently either camphor sulfonic acid or ammonium camphor sulfonate are used. The latter can be an unstable, slightly hygroscopic secondary standard compound with only one characterized CD band. The former is the very hygroscopic primary standard for which only one enantiomer is readily available. We have synthesized a new reference material for CD, Na[Co(EDDS)]·H2O (EDDS = N,N‐ethylenediaminedisuccinic acid) which addresses these problems. It is extremely stable and available in both enantiomeric forms. The CD spectrum of Na[Co(EDDS)]·H2O has nine distinct peaks between 180 and 599 nm. It thus fulfils the principal requirements for CD calibration chemical standards and has the potential to be used to ensure good practice in the measurement of CD data, providing two spectra of equal magnitude and opposite sign for a given concentration and path length. We have carried out an interlaboratory comparison using this material and show how it can be used to improve CD comparability between laboratories. A fitting algorithm has been developed to assess CD spectropolarimeter performance between 750 and 178 nm. This could be the basis of a formal quality control process once criteria for performance have been decided. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Highly enantioselective organocatalytic conjugate addition of nitromethane to benzylidene acetones
Authors: Szántó Gábor , Bombicz Petra , Grün Alajos , Kádas István 
Published: May 2008

AbstractSix active 4‐aryl‐5‐nitro‐pentan‐2‐ones were synthesized enantioselectively from the corresponding 5‐aryl‐butenones by asymmetric Michael addition of nitromethane using an imidazolidine‐type enantioselective organocatalyst. The ee ratio of the products were between 67 and 100%, determined by HPLC with Chiracel OD. Molecular and crystal structure of 3,4‐methylenedioxy‐phenyl‐5‐nitro‐pentan‐2‐one has been studied by single crystal X‐ray diffraction. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Diamagnetic lanthanide tris β‐diketonates as organic‐soluble chiral NMR shift reagents
Authors: Wenzel Thomas J. , Wenzel Bradford T. 
Published: May 2008

AbstractDiamagnetic lanthanium(III) and lutetium(III) tris β‐diketonate complexes of 3‐(trifluoroacetyl)‐d‐camphor, 3‐(heptafluorobutyryl)‐d‐camphor, and d,d‐dicampholylmethane are shown to be effective chiral NMR shift reagents for determining the enantiomeric purity of compounds with hard Lewis base functional groups. These include substrates with amine, alcohol, epoxide, sulfoxide, and oxaxolidine moieties. Enantiomeric discrimination is observed in the 1H NMR spectrum. Diamagnetic lanthanide complexes represent an alternative to paramagnetic varieties that often cause too much line broadening in the NMR spectra. The choice of which metal to use varies with substrate. Similarly, there is no consistent trend with ligand as not one of the complexes is consistently better than the others for all substrates. The enantiomeric discrimination also varies with solvent. Comparisons show that the chiral recognition was usually larger in benzene‐d6 than in chloroform‐d or cyclohexane‐d12. Chirality, 2009. © 2008 Wiley‐Liss, Inc.
Liquid chromatographic direct resolution of tocainide and its analogs on a (3,3′‐diphenyl‐1,1′‐binaphthyl)‐20‐crown‐6‐based chiral stationary phase containing residual silanol protecting n‐octyl groups
Authors: Choi Hee Jung , Jin Jong Sung , Hyun Myung Ho 
Published: May 2008

AbstractOptically active (3,3′‐diphenyl‐1,1′‐binaphthyl)‐20‐crown‐6‐based chiral stationary phase (CSP) containing residual silanol protecting n‐octyl groups on silica surface was applied to the liquid chromatographic direct resolution of tocainide and its analogs. The chiral recognition ability of the CSP was excellent, the separation (α) and the resolution factors (RS) for 15 analytes including tocainide being in the range of 3.02–22.92 and 3.94–20.41, respectively. In addition, the chiral recognition ability of the CSP was much greater than that of (3,3′‐diphenyl‐1,1′‐binaphthyl)‐20‐crown‐6‐based CSP containing residual silanol groups on the silica surface. The chromatographic behaviors for the resolution of tocainide and its analogs were found to be dependent on the content and the type of organic and acidic modifiers and the ammonium acetate concentration in aqueous mobile phase. Chirality, 2009. © 2008 Wiley‐Liss, Inc.
Conformation and absolute configuration of 2‐naphthylalkylsulfoxides by combined use of dynamic NMR, ECD spectroscopy, DFT computations, and X‐ray diffraction
Authors: Casarini Daniele , Lunazzi Lodovico , Mancinelli Michele , Mazzanti Andrea , Scafato Patrizia 
Published: May 2008

AbstractThe E/Z conformer ratios of five 2‐naphtylalkylsulfoxides were determined by means of dynamic NMR spectroscopy at very low temperatures and this information was used to predict, by means of DFT calculations, the ECD spectra of the R and S enantiomers. The latter were separated by enantioselective HPLC technique and the comparison of theoretical and experimental ECD spectra allowed the absolute configurations to be determined. In the case of 2‐naphtyl tert‐butylsulfoxide (1), the assignment was independently confirmed by anomalous dispersion using single crystal X‐ray crystallography. Chirality, 2009. © 2008 Wiley‐Liss, Inc.
Current and Foreseeable Applications of Supercritical Water for Energy and the Environment
Authors: Loppinet‐Serani Anne , Aymonier Cyril , Cansell François 
Published: May 2008

AbstractIt is crucial to develop economical and energy‐efficient processes for the sustainable transformation of biomass into fuels and chemicals. In this context, supercritical water biomass valorization (SCBV) processes are an alternative way to produce biogas, biofuels, and valuable chemicals. Supercritical water technology has seen much progress over the last fifteen years and an industrial application has merged: the supercritical water oxidation of wastes. The evolution from lab‐scale to pilot‐scale facilities has provided data on reaction mechanisms, kinetics, modeling, and reactor technology as well as an important know‐how, which can now be exploited to use the reactivity in supercritical water to transform biomass into gases (CO, H2, CO2, CH4, and N2) or into liquids (liquid fuel and valuable chemicals) with the supercritical water biomass gasification and liquefaction processes, respectively. This Review highlights the potential of SCBV processes to transform biomass into gas and liquid energy sources and highlights the developments that are still necessary to push this technology onto the market.
Drug design: hiding in full view
Authors: Radin Norman S. 
Published: May 2008

AbstractCompounds that can produce potent biological effects in cells encompass a variety of structural motifs. Many of these compounds share a structural feature that has rarely been noted. It is an allylic cluster of atoms, a 3‐carbon chain with a double bond between two of the atoms and an oxygen atom at the other end. The oxygen can be in a hydroxyl group, or in an ether or ketal or ester linkage, or simply a carbonyl form. In the latter case, the linkage is an allylic ketone (ene‐one) structure. Nitrogen is often seen in equivalent forms. Inclusion of at least one allylic moiety appears to be able to turn a modestly active or inert compound into an effective drug or toxin. Some compounds lack the allylic moiety but develop one by enzymatic action, usually via cytochrome P‐450 enzymes. These metabolites probably represent the active drug forms. The above concepts seem to be radically simplistic and improbable, but the evidence supporting them and the explanations for the biological activities are hidden “in plain view.” Comparisons with the pleiotropic activities of the allylic sphingolipid, ceramide, indicate that many allylic drugs operate by controlling the state of protein phosphorylation, by activating proteases, by generating reactive oxygen species, by slowing mitochondrial electron transport, or by lowering cellular glutathione concentrations. Drug Dev Res 69:15–25, 2008 © 2008 Wiley‐Liss, Inc.
Repeated neonatal separation stress alters the composition of neurochemically characterized interneuron subpopulations in the rodent dentate gyrus and basolateral amygdala
Authors: Seidel Katja , Helmeke Carina , Poeggel Gerd , Braun Katharina 
Published: May 2008

AbstractEmotional experience during early life has been shown to interfere with the development of excitatory synaptic networks in the prefrontal cortex, hippocampus, and the amygdala of rodents and primates. The aim of the present study was to investigate a developmental “homoeostatic synaptic plasticity” hypothesis and to test whether stress‐induced changes of excitatory synaptic composition are counterbalanced by parallel changes of inhibitory synaptic networks. The impact of repeated early separation stress on the development of two GABAergic neuronal subpopulations was quantitatively analyzed in the brain of the semiprecocial rodent Octodon degus. Assuming that PARV‐ and CaBP‐D28k‐expression are negatively correlated to the level of inhibitory activity, the previously described reduced density of excitatory spine synapses in the dentate gyrus of stressed animals appears to be “amplified” by elevated GABAergic inhibition, reflected by reduced PARV‐ (down to 85%) and CaBP‐D28k‐immunoreactivity (down to 74%). In opposite direction, the previously observed elevated excitatory spine density in the CA1 region of stressed animals appears to be amplified by reduced inhibition, reflected by elevated CaPB‐D28k‐immunoreactivity (up to 149%). In the (baso)lateral amygdala, the previously described reduction of excitatory spine synapses appears to be “compensated” by reduced inhibitory activity, reflected by dramatically elevated PARV‐ (up to 395%) and CaPB‐D28k‐immunoreactivity (up to 327%). No significant differences were found in the central nucleus of the amygdala, the piriform, and somatosensory cortices and in the hypothalamic paraventricular nucleus. Thus during stress‐evoked neuronal and synaptic reorganization, a homeostatic balance between excitation and inhibition is not maintained in all regions of the juvenile brain. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Differential expression of connexins during histogenesis of the chick retina
Authors: Kihara A.H. , Paschon V. , Akamine P.S. , Saito K.C. , Leonelli M. , Jiang J.X. , Hamassaki D.E. , Britto L.R.G. 
Published: May 2008

AbstractGap junction (GJ) channels couple adjacent cells, allowing transfer of second messengers, ions, and molecules up to 1 kDa. These channels are composed by a multigene family of integral membrane proteins called connexins (Cx). In the retina, besides being essential circuit element in the visual processing, GJ channels also play important roles during its development. Herein, we analyzed Cx43, Cx45, Cx50, and Cx56 expression during chick retinal histogenesis. Cx exhibited distinct expression profiles during retinal development, except for Cx56, whose expression was not detected. Cx43 immunolabeling was observed at early development, in the transition of ventricular zone and pigmented epithelium. Later, Cx43 was seen in the outer plexiform and ganglion cell layers, and afterwards also in the inner plexiform layer. We observed remarkable changes in the phosphorylation status of this protein, which indicated modifications in functional properties of this Cx during retinal histogenesis. By contrast, Cx45 showed stable gene expression levels throughout development and ubiquitous immunoreactivity in progenitor cells. From later embryonic development, Cx45 was mainly observed in the inner retina, and it was expressed by glial cells and neurons. In turn, Cx50 was virtually absent in the chick retina at initial embryonic phases. Combination of PCR, immunohistochemistry and Western blot indicated that this Cx was present in differentiated cells, arising in parallel with the formation of the visual circuitry. Characterization of Cx expression in the developing chick retina indicated particular roles for these proteins and revealed similarities and differences when compared to other species. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008
CD4+ T cell help improves CD8+ T cell memory by retained CD27 expression
Authors: Matter Matthias S. , Claus Christina , Ochsenbein Adrian F. 
Published: May 2008

AbstractCD4+ T cell help during the priming of CD8+ T lymphocytes imprints the capacity for optimal secondary expansion upon re‐encounter with antigen. Helped memory CD8+ T cells rapidly expand in response to a secondary antigen exposure, even in the absence of T cell help and, are most efficient in protection against a re‐infection. In contrast, helpless memory CTL can mediate effector function, but secondary expansion is reduced. How CD4+ T cells instruct CD8+ memory T cells during priming to undergo efficient secondary expansion has not been resolved in detail. Here, we show that memory CTL after infection with lymphocytic choriomeningitis virus are CD27high whereas memory CTL primed in the absence of CD4+ T cell have a reduced expression of CD27. Helpless memory CTL produced low amounts of IL‐2 and did not efficiently expand after restimulation with peptide in vitro. Blocking experiments with monoclonal antibodies and the use of CD27–/– memory CTL revealed that CD27 ligation during restimulation increased autocrine IL‐2 production and secondary expansion. Therefore, regulating CD27 expression on memory CTL is a novel mechanism how CD4+ T cells control CTL memory.
Generating functional CD8+ T cell memory response under transient CD4+ T cell deficiency: Implications for vaccination of immunocompromised individuals
Authors: Smith Corey , Martinez Michelle , Cooper Leanne , Rist Michael , Zhong Jie , Khanna Rajiv 
Published: May 2008

AbstractStudies based on either MHC class II‐knockout or CD4+ T cell‐depleted murine models have demonstrated a critical role for CD4+ T cells in the generation of CD8+ T cell memory. However, it is difficult to extend these findings to immunocompromised humans where a complete loss of CD4+ T cells is rarely observed. Here, we have developed a model setting, which allows studies on the generation of CD8+ T cell memory responses in a transient CD4+ T cell‐deficient setting similar to that seen in immunocompromised patients. Immunisation with an adenoviral vaccine under transient helpless or help‐deficient conditions showed varying degrees of impact on the priming of CD8+ T cell responses. Antigen‐specific T cells generated under normal CD4+ T cell help and transient help‐deficient conditions showed similar effector phenotype and were capable of proliferation upon secondary antigen encounter. Most importantly, in spite of CD4+ T cell deficiency, the long‐term CD8+ T cell memory response remained functionally stable and showed comparable cytotoxic effector function as seen in CD8+ T cells generated with normal CD4+ T cell numbers. These findings provide evidence that in spite of partially impaired activation of a primary CD8+ T cell response, a fully functional and stable memory CTL response can be induced under conditions of severe transient CD4+ T cell deficiency.
Blood CD8+ T cell responses against myelin determinants in multiple sclerosis and healthy individuals
Authors: Berthelot Laureline , Laplaud David‐Axel , Pettré Ségolène , Ballet Caroline , Michel Laure , Hillion Sophie , Braudeau Cécile , Connan Francine , Lefrère Fabienne , Wiertlewski Sandrine , Guillet Jean‐Gérard , Brouard Sophie , Choppin Jeannine , Soulillou Jean‐Paul 
Published: May 2008

AbstractPatients with multiple sclerosis (MS) display significant peripheral blood CD8+ T cell receptor biases, suggesting clonal selection. Our objective was to identify relevant myelin‐derived peptides capable of eliciting responses of fresh blood CD8+ T cells in MS patients. We focused our analysis on the HLA supertypes (HLA‐A3, ‐A2, ‐B7, ‐B27, ‐B44) predominant in a patient cohort. Three myelin protein (MBP, PLP and MOG) sequences were screened for HLA binding motifs and peptides were tested for their binding to HLA molecules. The cellular responses of 27 MS patients and 19 age‐ and sex‐matched healthy controls (HC) were tested in IFN‐γ ELISPOT assays only detecting pre‐committed CD8+ T cells. Sixty‐nine new epitopes elicited positive responses, with MOG‐derived peptides being the most immunogenic and peptides binding to HLA‐A3 being the most frequent. However, MS patients and HC displayed the same frequency of autoreactive cells. The epitopes inducing the strongest responses were not those with the highest HLA binding, suggesting an effective thymic selection in MS patients. Our data extend the concept that the frequency of myelin‐reactive T cells in MS patient blood is not increased compared to HC. The description of this set of myelin‐derived peptides (MHC class I restricted, recognized by CD8+ T cells) offers new tools to explore the CD8+ cell role in MS.
Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells
Authors: Gu Yongpeng , Yang Jianfei , Ouyang Xinshou , Liu Weicheng , Li Hongxing , Yang Jianjun , Bromberg Jonathan , Chen Shu‐Hsia , Mayer Lloyd , Unkeless Jay C. , Xiong Huabao 
Published: May 2008

AbstractIL‐17 and IL‐22 are typical cytokines produced by the Th17 T cell subset, but it is unclear if Th17 cytokines can be produced by other cell types. We demonstrate that IL‐10‐deficient and IL‐10R‐deficient macrophages stimulated with lipopolysaccharide produce high levels of IL‐17 and IL‐22. Addition of exogenous IL‐10 to IL‐10‐deficient macrophages abolished IL‐17 production. When IL‐10‐deficient and IL‐10R‐deficient splenocytes were cultured under Th17 polarizing conditions, the population of IL‐17‐producing cells was increased and the cultures produced significantly higher levels of IL‐17 and IL‐22. The addition of recombinant IL‐10 to IL‐10‐deficient splenocytes significantly decreased the percentage of IL‐17‐producing CD4+ T cells. Finally, the mRNA for the Th17 transcription factor retinoic acid‐related orphan receptor (ROR)γt was significantly elevated in IL‐10‐deficient spleen cells and macrophages. These data demonstrate that Th17 cytokines and RORγt are also expressed in macrophages and that IL‐10 negatively regulates the expression of Th17 cytokines and RORγt by both macrophages and T cells.