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At least 1,081 records · Page 60Linked to original sources
PubMed2005

Neutron powder diffraction study of Pb(HfxTi1-x)O3 ceramics (0.10<or=x<or=0.50).

The crystal symmetries of lead hafnate titanate (Pb(HfxTi1-x)O3, PHT) powders with 0.10<or=x<or=0.50 were investigated by high-resolution neutron powder diffraction. Samples with x<or=0.40 were tetragonal (space group P4 mm), while the sample with x=0.50 contained both monoclinic Cm and rhombohedral (modeled using the R3c space group) phases. The role of the B cations (Hf and Ti) and the oxygen octahedra network, in addition to the displacement of Pb ions from their ideal sites, in promoting the phase transformation between the P4 mm and Cm phases was considered. Two types of structural disorder were identified. Diffuse scattering between Bragg reflection peaks was assigned to Pb ion displacement. A second type of structural disorder, revealed by the weak intensities of observed pseudo-cubic 00l reflections with l even and as 00l reflection peak widths significantly broader than the l00 reflection peaks, was observed. This behavior was attributed to disorder in the arrangement of the O-B-O rows parallel to the c axis. For small values of x, this shift was predominantly along the c axis, whereas shifts perpendicular to the c axis increased with increasing x. These features were modeled using an hkl-dependent line-broadening model. The origin of the hkl-dependent line broadening was assigned to the microstrain accompanying a spatial-composition variation. Structural models were tested by computing valence sums and spontaneous polarization values.

Journal Article↗
PubMed2005

Effect of expanded graphite lattice in exfoliated graphite nanofibers on hydrogen storage.

A graphite exfoliation technique, using intercalation of a concentrated sulfuric/nitric acid mixture followed by a thermal shock, has successfully exfoliated a herringbone graphite nanofiber (GNF). The exfoliated GNF retains the overall nanosized dimensions of the original GNF, with the exfoliation temperature determining the degree of induced defects, lattice expansion, and resulting microstructure. High-resolution transmission electron microscopy indicated that the fibers treated at an intermediate temperature of 700 degrees C for 2 min had dislocations in the graphitic structure and a 4% increase in graphitic lattice spacing to 3.5 A. The fibers treated at 1000 degrees C for 36 h were expanded along the fiber axis, with regular intervals of graphitic and amorphous regions ranging from 0.5 to >50 nm in width. The surface area of the starting material was increased from 47 m(2)/g to 67 m(2)/g for the 700- degrees C treatment and to 555 m(2)/g for the 1000- degrees C treatment. Hydrogen uptake measurements at 20 bar indicate that the overall hydrogen uptake and operative adsorption temperature are sensitive to the structural variations and graphitic spacing. The increased surface area after the 1000- degrees C treatment led to a 1.2% hydrogen uptake at 77 K and 20 bar, a 3-fold increase in hydrogen physisorption of the starting material. The uptake of the 700- degrees C-treated material had a 0.29% uptake at 300 K and 20 bar; although low, this was a 14-fold uptake over the starting material and higher than other commonly used pretreatment methods that were tested in parallel. These results suggest that selective exfoliation of a nanofiber is a means by which to control the relative binding energy of the hydrogen interaction with the carbon structure and thus vary the operative adsorption temperature.

Journal Article↗
PubMed1997

Characterization of mitochondrial small-subunit ribosomal RNAs from holoparasitic plants.

Mitochondrial small-subunit (19S) rDNA sequences were obtained from 10 angiosperms to further characterize sequence divergence levels and structural variation in this molecule. These sequences were derived from seven holoparasitic (nonphotosynthetic) angiosperms as well as three photosynthetic plants. 19S rRNA is composed of a conservative core region (ca. 1450 nucleotides) as well as two variable regions (V1 and V7). In pairwise comparisons of photosynthetic angiosperms to Glycine, the core 19S rDNA sequences differed by less than 1.4%, thus supporting the observation that variation in mitochondrial rDNA is 3-4 times lower than seen in protein coding and rDNA genes of other subcellular organelles. Sequences representing four distinct lineages of nonasterid holoparasites showed significantly increased numbers of substitutions in their core 19S rDNA sequences (2.3-7.6%), thus paralleling previous findings that showed accelerated rates in nuclear (18S) and plastid (16S) rDNA from the same plants. Relative rate tests confirmed the accelerated nucleotide substitution rates in the holoparasites whereas rates in nonparasitic plants were not significantly increased. Among comparisons of both parasitic and nonparasitic plants, transversions outnumbered transitions, in many cases more than two to one. The core 19S rRNA is conserved in sequence and structure among all nonparasitic angiosperms whereas 19S rRNA from members of holoparasitic Balanophoraceae have unique extensions to the V5 and V6 variable domains. Substitution and insertion/deletion mutations characterized the V1 and V7 regions of the nonasterid holoparasites. The V7 sequence of one holoparasite (Scybalium) contained repeat motifs. The cause of substitution rate increases in the holoparasites does not appear to be a result of RNA editing, hence the underlying molecular mechanism remains to be fully documented.

Base Composition↗
PubMed1987

Redox chemistry of the 9-anilinoacridine class of antitumor agents.

9-Anilinoacridines bearing a 1'-NHR substituent on the anilino ring undergo facile, chemically reversible, two-electron oxidation to quinone diimines. The chemical and electrochemical oxidation of three groups of 9-anilinoacridines (1'-substituted derivatives, together with 3'-substituted analogues and acridine-substituted analogues of the clinical antileukemic drug amsacrine) have been studied and their redox potentials determined. For aniline-substituted derivatives, redox potentials (E1/2) correlate well with substituent electronic properties, with electron-donating substituents facilitating oxidation. Substituents in the acridine ring have little effect on redox potentials, indicating minimal transmission of electronic effects from the acridine to the aniline rings. Although the broad class of 9-anilinoacridines show biological activity over a very wide range of structural variations, a 1'-NHR substituent is a common feature of the most active derivatives. Nevertheless, no clear quantitative relationships between redox potential and biological activity could be discerned, and the relevance of this redox chemistry to the mode of action of amsacrine and other 9-anilinoacridines remains unclear.

Aminoacridines↗
PubMed1996

Aspirin-DNA interaction studied by FTIR and laser Raman difference spectroscopy.

The interaction of calf-thymus DNA with aspirin is investigated in aqueous solution at pH 7-6 with drug/DNA (phosphate) molar ratios of r = 1/40, 1/20, 1/10, 1/5, 1/2, 1 and 2. Fourier transform infrared (FTIR) and laser Raman difference spectroscopy are used to determine drug binding sites, sequence preference and DNA secondary structure, as well as the structural variations of aspirin-DNA complexes in aqueous solution. Spectroscopic evidence showed that at low aspirin concentration (r =1/40), drug-DNA interaction is mainly through the backbone PO2 groups and the A-T base pairs. Such interaction largely perturbs the phosphate vibration at 1222 cm(-1) and the A-T bands at 1663 and 1609 cm(-1) with no major helix destabilization. At higher drug concentration (r > 1/20), the participation of the G-C bases in drug-DNA complexation was evident by strong perturbations of the guanine and cytosine vibrations at 1717 and 1494 cm(-1), with a partial helix destabilization. A major alteration of the B-DNA structure towards A-DNA occurs on drug complexation. The aspirin interaction was through anion CO and COOCH3 donor atoms with those of the backbone PO2 group and DNA bases donor sites (directly or indirectly via H2O molecules).

Animals↗
PubMed2006

Membrane and juxtamembrane targeting by PH and PTB domains.

Modular pleckstrin homology (PH) and phospho-tyrosine binding (PTB) domains are present in a remarkably large number of proteins from yeast to humans. With a common core fold, these domain families have evolved to recognize membrane embedded phospholipids, in particular phosphoinositides, peripheral membrane proteins, and peptide motifs in juxtamembrane regions of integral membrane proteins. As the result of intensive investigation using biochemical, biophysical, and structural approaches, common ligand recognition principles have emerged along with insights into the structural variations that account for the diversity of ligand specificities. Analyses of membrane targeting in cells have revealed additional determinants beyond the primary ligand binding sites. In this review, we highlight unifying recognition principles and further illustrate with examples how divergent mechanisms contribute to membrane and juxtamembrane targeting by PH and PTB domains.

Binding Sites↗
PubMed2006

Symmetry breaking in interspecific Drosophila hybrids is not due to developmental noise.

Hybrids from crosses of different species have been reported to display decreased developmental stability when compared to their pure species, which is conventionally attributed to a breakdown of coadapted gene complexes. Drosophila subobscura and its close relative D. madeirensis were hybridized in the laboratory to test the hypothesis that genuine fluctuating asymmetry, measured as the within-individual variance between right and left wings that results from random perturbations in development, would significantly increase after interspecific hybridization. When sires of D. subobscura were mated to heterospecific females following a hybrid half-sib breeding design, F1 hybrid females showed a large bilateral asymmetry with a substantial proportion of individuals having an asymmetric index larger than 5% of total wing size. Such an anomaly, however, cannot be plainly explained by an increase of developmental instability in hybrids but is the result of some aberrant developmental processes. Our findings suggest that interspecific hybrids are as able as their parents to buffer developmental noise, notwithstanding the fact that their proper bilateral development can be harshly compromised. Together with the low correspondence between the co-variation structures of the interindividual genetic components and the within-individual ones from a Procrustes analysis, our data also suggest that the underlying processes that control (genetic) canalization and developmental stability do not share a common mechanism. We argue that the conventional account of decreased developmental stability in interspecific hybrids needs to be reappraised.

Animals↗
PubMed1999

Novel arylpyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides as platelet aggregation inhibitors. 2. Optimization by quantitative structure-activity relationships.

In the previous paper (Part 1), we described the synthesis and antiplatelet activity of a series of phenyl- and heteroarylpyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides. In this paper, we report the optimization of the platelet aggregation inhibitory activity by an iterative sequence of quantitative structure-activity relationship studies which encompassed synthesis and evaluation of the effects of structure variations at the 1-, 6-, and 7-positions of the heterocyclic system. A model has been established that correctly correlates antiplatelet activity in this series with the partial atomic charges calculated by a local density functional ab initio method. As a result of this study, the experimental platelet aggregation inhibitory activity of the lead compound was improved 300-fold.

Animals↗
PubMed1976

Quantitative variations of three different lectin receptors as a function of establishment and metabolism of normal and leukaemic human cell lines.

Lectin binding on the cell surface was measured by the method of Kornfeld [16] using three tritiated lectins: Robinia pseudo acacia, Concanavalin A and Ricinus. It has been shown that the number of binding sites for Robinia and Con A decreases after the establishment of a leukaemic cell line, whereas the affinity constant increases for Robinia. The relationship between lectin binding and cell growth was carried out on 5 cell lines, 3 of leukaemic and 2 of normal origin. In all cases the maximum number of sites was determined at the time of doubling for the cell population; the affinity constant reciprocally decreases at this moment. For Robinia, a difference was found in both cell growth and the number of sites between an Epstein-Barr virus (EBV) negative leukaemic cell line and the other EBV positive cell lines. Lectins offer a quantitative method for measuring membrane structure variations during and after establishment of cell lines.

Animals↗
PubMed1995

Does DNA acid fixation produce left-handed Z structure?

The effects of acetic acid (HCOOCH3) on the solution structure of calf-thymus DNA are studied at pH 7.3-2.5 with acid/DNA(P) (phosphate) molar ratios (r) of 1/40, 1/20, 1/10, 1, 2, 10, 20 and 40. Fourier Transform infrared (FTIR) difference spectroscopy is used to establish correlations between spectral changes and base protonation, DNA conformational transition and structural variations of the acid-DNA complexes in aqueous solution. The FTIR difference spectroscopic results showed that protonation of cytosine and subsequent unpairing of the G-C base pairs begins at pH 4-3 and continues up to pH 2.5, where a complete base separation and base unstacking occur. Similarly, protonation of A-T base pairs starts at pH 4-3 and is completed at pH 2.5, where base separation and base unstacking are observed. The protonation of the G-C base pair leads to the formation of Hoogsteen-type H-bonding, before a complete G-C disruption. The biopolymer protonation leads to the formation of several non-B-DNA structures, including left-handed Z conformation.

Animals↗
PubMed2005

Structure-activity relationships, kinetics, selectivity, and mechanistic studies of synthetic hydraphile channels in bacterial and mammalian cells.

Hydraphile compounds are shown to be cytotoxic to Gram-negative and Gram-positive bacteria, yeast, and mammalian cells. Their cellular toxicity compares favorably with other synthetic ionophores and rivals that potency of natural antibiotics. The effects of structural variations on toxicity are described. The effects of these variations correlate well with previous studies of ion transport in liposomes. Whole cell patch clamping with mammalian cells confirms a channel mechanism in living cells suggesting that this family may comprise novel and flexible pharmacological agents.

Animals↗
PubMed2005

Stabilization of somatropin by heparin.

Somatropin, human growth hormone (hGH), is an unstable protein, posing challenging problems for its formulation and long-term stability. Since hGH formed insoluble adducts with heparin our aim was to evaluate heparin as a stabilizing agent for the drug. These adducts were characterized by particle diameter, tertiary structure variations and release studies. Studies were also carried out to determine the stability of hGH in the presence and absence of heparin by an interfacial denaturation method and real-time stability studies by measuring hGH activity and particle diameter. Moreover, biological activity of hGH and hGH/UH (unfractionated heparin) adducts was identified by daily subcutaneous injections to hypophysectomized rats. There was a decrease in mean hydrodynamic particle diameter of hGH/UH adducts with increased pH (54.4 to 12.2 nm from pH 3 to pH 7) indicating that the adducts were either dissociating or dissolving at high pH. Furthermore, second-derivative spectroscopy indicated that complexation of hGH with heparin did not cause a major disruption in the tertiary structure of hGH but decreased the hydrophilic environment around the tyrosine residues. Release of hGH from hGH/UH adducts was pH and ionic strength dependent with the highest release at pH 8 (93%) and lowest release at pH 3 (0%) over the first hour. Interfacial denaturation methods indicated that vortex agitation over 120 s resulted in no change in the optical density of hGH/UH adducts compared with a substantial increase for hGH alone at pH 6.8. Real-time stability studies over 93 days demonstrated that hGH/UH adducts at both pH 3 and 7 with an excess of heparin produced the highest percent of active hGH remaining in the solution at 4 degrees C and 37 degrees C. The higher stability of hGH/UH adducts with excess heparin compared with the stoichiometric ratio was also confirmed by particle size measurements during storage. The biological activity of these adducts was comparable with hGH alone by weight-gain studies in hypophysectomized rats. The findings suggest the value of using hGH/heparin adducts to stabilize the protein.

Animals↗
PubMed1995

Kinetic and structural characterization of mutations of glycine 216 in alpha-lytic protease: a new target for engineering substrate specificity.

Gly216 in the active site of the broadly specific MA190 mutant of alpha-lytic protease has been found to be remarkably tolerant of amino acid substitutions. Side-chains as large as Trp can be accommodated within the substrate-binding pocket without abolishing catalysis, and have major effects upon the substrate specificity of the enzyme. Kinetic characterization of eleven enzymatically active mutants against a panel of eight substrates clearly revealed the functional consequences of the substitutions at position 216. To understand better the structural basis for their altered specificity, the GA216 + MA190 and GL216 + MA190 mutants have been crystallized both with and without a representative series of peptide boronic acid transition-state analog inhibitors. An empirical description and non-parametric statistical analysis of structural variation among these enzyme: inhibitor complexes is presented. The roles of active site plasticity and dynamics in alpha-lytic protease function and substrate preference are also addressed. The results strongly suggest that substrate specificity determination in alpha-lytic protease is a distributed property of the active site and substrate molecule.

Boron Compounds↗
PubMed2002

Rho-kinase inhibitors: pharmacomodulations on the lead compound Y-32885.

In order to specify structure-activity relationships we have synthesized new series of analogues of the Rho-kinase inhibitor (R)-(+)-N-(4-pyridyl)-4-(1-aminoethyl)benzamide (Y-32885). The structural modifications concerned the 1-aminoethyl, the pyridyl and the amide groups which are the main features of this lead compound. Our analogue derivatives were evaluated on GTPgammaS-induced contraction in permeabilized smooth-muscle and on the actin cytoskeleton. All the modifications result in a diminution or a loss of activity showing that interactions of Y-32885 with the catalytic domain of Rho-kinase seem to be particularly definite and sensitive to structural variations. The presence of a pyridine moiety and a basic amine group separated by a spacer bearing an amide function are of utmost importance.

Actins↗
PubMed1986

Protein dynamics investigated by neutron diffraction.

The most correct model of the molecular structure of a protein molecule is one which describes it as having a number of variable conformational states. These states differ in degree over a large spectrum of structural variation ranging from individual atomic vibrational motion to significant tertiary denaturation. The application of the neutron diffraction techniques discussed above dealt with two classes of conformational fluctuation, "protein breathing" and "regional melting." The utility of the neutron technique stems from the ability to locate hydrogen atoms and to discriminate between hydrogens and deuteriums. This latter attribute allows for performing H/D exchange experiments by identifying individual sites of exchange. With this information it has been possible to discern which regions of the protein molecule undergo regional melting. Protein breathing was explored by analyzing the rotational properties of side chain methyl groups. Such information clearly suggested that most of these groups reside in "staggered" (low energy) conformation in the time averaged structure and are not greatly affected by local structural packing. Together these two classes of conformational fluctuation span nearly the full range of all motions that might play a role in biological activity. Information about such motions can be obtained from other types of physicochemical methods, but in most cases the interpretation of the data is considerably less definitive than that which can be obtained from a neutron analysis.

Crystallography↗
PubMed2006

Antitumor benzothiazoles. 26.(1) 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (GW 610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon, and breast cancer cell lines.

A series of new 2-phenylbenzothiazoles has been synthesized on the basis of the discovery of the potent and selective in vitro antitumor properties of 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (8n; GW 610, NSC 721648). Synthesis of analogues substituted in the benzothiazole ring was achieved via the reaction of o-aminothiophenol disulfides with substituted benzaldehydes under reducing conditions. Compounds were evaluated in vitro in four human cancer cell lines, and compound 8n was found to possess exquisitely potent antiproliferative activity (GI(50) < 0.1 nM for MCF-7 and MDA 468). Potent and selective activity was also observed in the NCI 60 human cancer cell line panel. Structure-activity relationships established that the compound 8n stands on a pinnacle of potent activity, with most structural variations having a deactivating in vitro effect. Mechanistically, this new series of agents contrasts with the previously reported 2-(4-aminophenyl)benzothiazoles; compound 8n is not reliant on induction of CYP1A1 expression for antitumor activity.

Antineoplastic Agents↗
PubMed1999

Structure, specificity and CDR mobility of a class II restricted single-chain T-cell receptor.

Using NMR spectroscopy, we determined the solution structure of a single-chain T-cell receptor (scTCR) derived from the major histocompatibility complex (MHC) class II-restricted D10 TCR. The conformations of complementarity-determining regions (CDRs) 3beta and 1alpha and surface properties of 2alpha are different from those of related class I-restricted TCRs. We infer a conserved orientation for TCR V(alpha) domains in complexes with both class I and II MHC-peptide ligands, which implies that small structural variations in V(alpha) confer MHC class preference. High mobility of CDR3 residues relative to other CDR or framework residues (picosecond time scale) provides insight into immune recognition and selection mechanisms.

Amino Acid Sequence↗