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Conformational Structure (conformational + structure)
Selected AbstractsConformational Structure and Energetics of 2-Methylphenyl(2,-methoxyphenyl)iodonium Chloride: Evidence for Solution ClustersCHEMISTRY - A EUROPEAN JOURNAL, Issue 34 2010Dr. Yong-Sok Lee Abstract Diaryliodonium salts allow the efficient incorporation of cyclotron-produced [18F]fluoride ions into electron-rich and electron-deficient arenes to provide potential radiotracers for molecular imaging in vivo with positron emission tomography (PET). This process (ArI+Ar,+18F,,Ar18F+Ar,I) is still not well understood mechanistically. To better understand this and similar reactions, it would be valuable to understand the structures of diaryliodonium salts in organic media, where the reactions are typically conducted. In this endeavor, the X-ray structure of a representative iodonium salt, 2-methylphenyl(2,-methoxyphenyl)iodonium chloride (1), was determined. Our X-ray structure analysis showed 1 to have the conformational M,P dimer as the unit cell with hypervalent iodine as a stereogenic center in each conformer. With the ab initio replica path method we constructed the inversion path between the two enantiomers of 1, thereby revealing two additional pairs of enantiomers that are likely to undergo fast interconversion in solution. Also LC,MS of 1 showed the presence of dimeric and tetrameric anion-bridged clusters in weak organic solution. This observation is consistent with the energetics of 1, both as monomeric and dimeric forms in MeCN, calculated at the B3LYP/DGDZVP level. These evidences of the existence of dimeric and higher order clusters of 1 in solution are relevant to achieve a deeper general understanding of the mechanism and outcome of reactions of diaryliodonium salts in organic media with nucleophiles, such as the [18F]fluoride ion. [source] Capillary electrophoretic study of the binding of zinc(II) ion to bacitracin A1 in water-2,2,2-trifluoroethanolELECTROPHORESIS, Issue 10 2003Massimo Castagnola Abstract Binding of Zn2+ to bacitracin A1 was studied by capillary electrophoresis in water/2,2,2-trifluoroethanol (70/30 v/v) at different apparent pH values in order to estimate the association constant of metal, the acidic dissociation constants and the Stokes radii of both free and bounded peptide in apolar environment. The Stokes radii of the free peptide species were compared with those in aqueous solution, as obtained in a recent study performed by our group, indicating that apolar environment stabilizes bacitracin A1 in a conformational structure with the lateral chain of apolar amino acids exposed on the external surface. This conformation of the macrocyclic dodecapeptide is ready to interact with Zn2+ ion, as pointed out by the strong increase of the association constant measured in water/2,2,2-trifluoroethanol with respect to the value obtained in aqueous solution. In addition, whereas Zn2+ ion binding in aqueous solution provides a sensible reduction of peptide Stokes radius, no sensible variations following to ion binding were observed in hydro-organic solution. The present results suggest that the apolar environment, rather than the metal ion binding, could be responsible for the conformational transition that brings bacitracin A1 towards its biologically active structure.* [source] Inverse Monte Carlo procedure for conformation determination of macromoleculesJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 7 2003Mark Bathe Abstract A novel numerical method for determining the conformational structure of macromolecules is applied to idealized biomacromolecules in solution. The method computes effective inter-residue interaction potentials solely from the corresponding radial distribution functions, such as would be obtained from experimental data. The interaction potentials generate conformational ensembles that reproduce thermodynamic properties of the macromolecule (mean energy and heat capacity) in addition to the target radial distribution functions. As an evaluation of its utility in structure determination, we apply the method to a homopolymer and a heteropolymer model of a three-helix bundle protein [Zhou, Y.; Karplus, M. Proc Natl Acad Sci USA 1997, 94, 14429; Zhou, Y. et al. J Chem Phys 1997, 107, 10691] at various thermodynamic state points, including the ordered globule, disordered globule, and random coil states. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 876,890, 2003 [source] The impact of the pH value on skin integrity and cutaneous wound healingJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2010S Schreml Abstract The process of cutaneous wound healing comprises three overlapping major phases: inflammation, proliferation and tissue remodelling. However, while mechanisms are studied scientifically on the cellular and subcellular level, there is still a lack of knowledge concerning basic clinical parameters like wound pH or pO2. It could be proven that wound healing is affected by wound pH changes as they can lead to an inhibition of endogenous and therapeutically applied enzymes. Besides, the conformational structure of proteins and their functionality in wound healing is altered. Furthermore, the likelihood of bacterial colonization, which is a common problem in chronic wound pathogenesis, is affected by wound pH alterations. However, wound pH is rarely taken into account in current wound therapy strategies. A routinely performed monitoring of the wound pH and a subsequently adapted wound therapy would most possibly improve chronic wound therapy. [source] The impact of pollen-related food allergens on pollen allergyALLERGY, Issue 1 2007B. Bohle Patients with birch pollen allergy frequently develop hypersensitivity reactions to certain foods, e.g. apples, celery, carrots and hazelnuts. These reactions are mainly caused by IgE-antibodies specific for the major birch pollen allergen, Bet v 1, which cross-react with homologous proteins in these foods. Analyzing the T-cell response to Bet v 1-related food allergens revealed that these dietary proteins contain several distinct T-cell epitopes and activate Bet v 1-specific T cells to proliferate and produce cytokines. Several of these cross-reactive T-cell epitopes were not destroyed by simulated gastrointestinal digestion of food allergens and stimulated Bet v 1-specific T cells despite nonreactivity with IgE antibodies. Similarly, cooked food allergens did not elicit IgE-mediated symptoms (oral allergy syndromes) but caused T-cell-mediated late-phase reactions (deterioration of atopic eczema) in birch pollen-allergic patients with atopic dermatitis because thermal processing affected their conformational structure and not the primary amino acid sequence. Thus, T-cell cross-reactivity between Bet v 1 and related food allergens occurs independently of IgE-cross-reactivity in vitro and in vivo. We speculate that symptom-free consumption of pollen-related food allergens may have implications for the pollen-specific immune response of allergic individuals. [source] Von Willebrand factor protects the Ca2+ -dependent structure of the factor VIII light chainBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2009Masahiro Takeyama Summary We have recently reported that cation-exchange iminodiacetate resin completely inactivated factor VIII (FVIII) by direct deprivation of metal ions, predominantly Ca2+, from its molecules, and that von Willebrand factor (VWF) protected FVIII antigen from resin-induced degradation. The present study was further developed to investigate this mechanism. Western blotting analysis and enzyme-linked immunosorbent assay showed that the antigenic structure of the FVIII light chain, especially the C2 domain, was completely impaired by the resin, whilst that of the heavy chain was little affected. However, the complex formation with VWF protected the C2 domain from the resin-induced degradation. The resin-treated C2 domain failed to interact with VWF and phospholipid. Furthermore, the addition of Ca2+ competitively blocked the resin-induced impairment of the C2 domain structure. These results demonstrate that VWF protects the Ca2+ -dependent conformational structure of the FVIII light chain, especially the C2 domain, and may indicate that the C2 domain contains the Ca2+ -binding site(s). [source] Therapeutic antitumor efficacy of monoclonal antibody against Claudin-4 for pancreatic and ovarian cancersCANCER SCIENCE, Issue 9 2009Masayo Suzuki Claudin-4 (CLDN4) is a tetraspanin transmembrane protein of tight junction structure and is highly expressed in pancreatic and ovarian cancers. In this study, we aimed to generate an anti-Claudin-4 monoclonal antibody (mAb) and evaluate its antitumor efficacy in vitro and in vivo. To isolate specific mAb, we generated CLDN3, 4, 5, 6, and 9, expressing Chinese hamster ovary (CHO) cells, and then used them as positive and negative targets through cell-based screening. As a result, we succeeded in isolating KM3900 (IgG2a), which specifically bound to CLDN4, from BXSB mice immunized with pancreatic cancer cells. Immunoprecipitation and flow cytometry analysis revealed that KM3900 recognized the conformational structure and bound to extracellular loop 2 of CLDN4. Furthermore, binding of KM3900 was detected on CLDN4-expressing pancreatic and ovarian cancer cells, but not on negative cells. Next, we made the mouse,human chimeric IgG1 (KM3934) and evaluated its antitumor efficacy. KM3934 induced dose-dependent antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro, and significantly inhibited tumor growth in MCAS or CFPAC-1 xenograft SCID mice in vivo (P < 0.05). These results suggest that mAb therapy against CLDN4 is promising for pancreatic and ovarian cancers. (Cancer Sci 2009; 100: 1623,1630) [source] Immobilization and Characterization of Glucose Oxidase on Single-Walled Carbon Nanotubes and Its Application to Sensing GlucoseCHINESE JOURNAL OF CHEMISTRY, Issue 4 2007Shu-Na Liu Abstract The negatively charged (at pH 8.2) glucose oxidase (GOx, pI ca. 4.2) was assembled onto the surface of single-walled carbon nanotubes (SWNT), which was covered (or wrapped) by a layer of positively charged polyelectrolyte poly(dimethyldiallylammonium chloride) (PDDA), via the electrostatic interaction forming GOx-PDDA- SWNT nanocomposites. Fourier transform infrared (FTIR), UV-Vis and electrochemical impedance spectroscopy (EIS) were used to characterize the growth processes of the nanocomposites. The results indicated that GOx retained its native secondary conformational structure after it was immobilized on the surface of PDDA-SWNT. A biosensor (Nafion-GOx-PDDA-SWNT/GC) was developed by immobilization of GOx-PDDA-SWNT nanocomposites on the surface of glassy carbon (GC) electrode using Nafion (5%) as a binder. The biosensor showed the electrocatalytic activity toward the oxidation of glucose under the presence of ferrocene monocarboxylic acid (FcM) as an electroactive mediator with a good stability, reproducibility and higher biological affinity. Under an optimal condition, the biosensor could be used to detection of glucose, presenting a typical characteristic of Michaelis-Menten kinetics with the apparent Michaelis-Menten constant of KappMca. 4.5 mmol/L, with a linear range of the concentration of glucose from 0.5 to 5.5 mmol/L (with correlation coefficient of 0.999) and the detection limit of ca. 83 µmol/L (at a signal-to-noise ratio of 3). Thus the biosensor was useful in sensing the glucose concentration in serum since the normal glucose concentration in blood serum was around 4.6 mmol/L. The facile procedure of immobilizing GOx used in present work would promote the developments of electrochemical research for enzymes (proteins), biosensors, biofuel cells and other bioelectrochemical devices. [source] Discrimination between diastereoisomeric dipeptides by IR,UV double resonance spectroscopy and ab initio calculationsINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4 2005Ali G. Abo-Riziq Abstract We studied diastereoisomeric dipeptides, containing two chiral centers, by comparing ab initio calculations with laser desorption jet-cooling experiments. We studied the hetero-dipeptides LL,VF (L-Val-L-Phe) and DL,VF and the homo-dipeptides LL,FF (L-Phe-L-Phe) and LD,FF. Changing one of the chiral centers in each molecule leads to changes in the spectra that can be used to distinguish between diastereoisomeric pairs. We observed three different conformers for LL,VF, four for DL,VF, two for LL,FF, and one for LD,FF. By comparing the results from IR,UV double resonant spectroscopy with ab initio calculations, we can draw conclusions about the conformational structures. At the same time, the experimental data serve as a test for the computational results. We discuss the possibilities and limitations of the interplay between theory and experiment. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005 [source] Methylazacalixpyridines: Remarkable Bridging Nitrogen-Tuned Conformations and Cavities with Unique Recognition PropertiesCHEMISTRY - A EUROPEAN JOURNAL, Issue 36 2006Han-Yuan Gong Abstract Methylazacalix[n]pyridines (n = 4, 8) and methylazacalix[m]arene[n]pyridines (m = n = 2, 4) have been synthesized by a convenient fragment coupling approach starting from 2,6-dibromopyridine, 2,6-diaminopyridine, and benzene-1,3-diamine. Thanks to the intrinsic electronic nature of nitrogen, which can adopt mainly sp2 hybridization, allowing it variously to conjugate, partially conjugate, or not conjugate with the adjacent one or two pyridine rings, the resulting nitrogen-bridged calixpyridine derivatives act as a unique class of macrocyclic host molecules with intriguing conformational structures offering fine-tunable cavities and versatile recognition properties. Whilst in solution it is fluxional, in the solid state methylazacalix[4]pyridine adopts a 1,3-alternate conformation with a C2v symmetry in which every two bridging nitrogen atoms conjugate with one pyridine ring. After protonation, the methylazacalix[4]pyridinium species has a different conjugation system of its four bridging nitrogen atoms, yielding the similar twisted 1,3-alternate conformations with an approximate S4 symmetry. The cavity of each protonated methylazacalix[4]pyridine, however, varies finely to accommodate guest species of different size and geometry, such as planar DMF or HO2CCO2, ion, a twisted HO2CCO2, ion, and a tetrahedral ClO4, ion. As giant macrocyclic hosts, both methylazacalix[8]pyridine and methylazacalix[4]arene[4]pyridine interact efficiently with fullerenes C60 and C70 through van der Waals forces. Their ease of preparation, versatile conformational structures, and recognition properties make these multinitrogen-containing calixarenes or cyclophanes unique and powerful macrocyclic hosts in supramolecular chemistry. [source] | |||||||||||||