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Acid Structures (acid + structure)
Kinds of Acid Structures Selected AbstractsRegulation of multidrug resistance 2 P-glycoprotein expression by bile salts in rats and in primary cultures of rat hepatocytesHEPATOLOGY, Issue 2 2000Seema Gupta Biliary phospholipid secretion is tightly coupled to the secretion of free cholesterol and bile salts. The secretion of phospholipids across the canalicular membrane of hepatocytes occurs via the multidrug resistance 2 (mdr2) P-glycoprotein (Pgp). The mechanism underlying the coupling of bile salt and phospholipid secretion has not been elucidated. The aims of this study were to determine the effects of bile acid structure on the expression of mdr2 in vitro and in vivo. Under optimal culture conditions, taurine-conjugated bile acids (50 ,mol/L) increased mdr2 messenger RNA (mRNA) levels in the following order: taurocholate (TCA) (288 ± 36%, P < .005) = taurodeoxycholate (TDCA) (276 ± 36%, P < .025) > taurochenodeoxycholate (TCDCA) (216 ± 34%, P < .025) > tauroursodeoxycholate (TUDCA) (175 ± 28%, P < .05) of control levels. The increase in mdr2 mRNA levels by TCA was both time and concentration dependent. Cholate feeding to rats with intact enterohepatic circulation increased mdr2 transcriptional activity by 4-fold and protein mass by 1.9-fold. Chronic biliary diversion (CBD) decreased mdr2 mRNA levels to 66 ± 9% (P < .025) of sham-operated controls. Intraduodenal infusion of TCA for 48 hours in CBD rats caused a significant increase in mdr2 mRNA levels (224%) as compared with CBD controls. A diet high in cholesterol (4%) decreased mdr2 mRNA levels to 57% ± 2 (P < .001) of pair-fed controls. Squalestatin (1 ,mol/L), an inhibitor of cholesterol biosynthesis, increased mdr2 mRNA levels by 8.8-fold (P < .005) in hepatocyte cultures after 24 hours. In conclusion, in the rat, bile acids up-regulated mdr2 transcriptional activity whereas cholesterol decreased mdr2 mRNA both in vitro and in vivo. [source] Direct-temperature mass spectrometric detection of volatile terpenoids and natural terpenoid polymersin fresh and artificially aged resinsJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 6 2003Dominique Scalarone Abstract Electron impact (EI) ionization and ammonia chemical ionization (NH3/CI) direct-temperature mass spectrometry (DTMS) was used to characterize five natural terpenoid resins: dammar, mastic, colophony, Manila copal and sandarac. Compositional differences were highlighted by the identification of low molecular mass compounds, ranging from di- to triterpenoids, and polymeric components, based on polycadinene and polycommunic acid. Photo-ageing processes occurring under accelerated indoor and outdoor exposure conditions were also investigated. NH3/CI and tetramethylammonium hydroxide EI were applied to increase the sensitivity towards highly oxidized molecules. Oxidation and cross-linking reactions were found to affect mostly triterpenoid resins and diterpenoid abietane and pimarane molecules. Oxidation proceeds through a radical mechanism, generally starting from conjugated double bonds. Oxygen atoms are incorporated in the terpenoid structures in the form of alcohols, ketones and carboxylic acids. Oxidized cadinene oligomers released by pyrolytic degradation of the polycadinene fraction of dammar were detected even in unaged samples. Evidence is given indicating the occurrence of cleavages in the cross-linked polycommunic structure of aged sandarac and Manila copal. Bond scissions produce oligomeric fragments based on the communic acid structure and sufficiently volatile to be desorbed at low temperature in DTMS measurements. Copyright © 2003 John Wiley & Sons, Ltd. [source] Stability and hydrolysis kinetics of spirosuccinimide type inhibitors of aldose reductase in aqueous solution and retardation of their hydrolysis by the target enzymeJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2008Masuo Kurono Abstract The stability and the hydrolysis kinetics of spirosuccinimide type aldose reductase (AR) inhibitors, SX-3030 (racemate) and its optical enantiomers (R - and S -isomers), were investigated in aqueous solution. The hydrolysis followed pseudo-first-order kinetics and showed significant pH dependence. Maximum solution stability was observed below pH 2.4, whereas the hydrolysis was gradually catalyzed by hydroxide ion at neutral to alkaline pH while the compounds exhibiting moderate pH-independent stability at acidic to neutral conditions (pH 4,7) to enable oral administration. A pK of 3.7 was obtained from the pH-rate profile, but this kinetically derived pK is approximately 2 pH units below the pK of the parent compounds, suggesting the presence of an acidic intermediate involved in the hydrolysis process. These findings, together with structural analysis, support the notion that the hydrolysis would proceed via nucleophilic attack of a water molecule or hydroxide ion on the scissile carbonyl bond of the succinimide ring to form a succinamic acid intermediate that has a ,-keto acid structure, followed by decarboxylation to give a racemized succinimide ring-opened product. On the other hand, the interconversion of the R - and S -isomers did not occur during hydrolysis; however, the hydrolysis of the R -isomer was markedly suppressed by the target enzyme AR whereas that of the S -isomer was not, indicating a high degree of complementarity of interacting surfaces between the R -isomer and the enzyme. The results in the present study could provide useful clues for facilitating the appropriate stabilization strategies as well as for evaluating the pharmacological effects on target tissues in vivo, and suggested that the R -isomer may be a suitable candidate as AR inhibitor. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1468,1483, 2008 [source] Motifs in nucleic acids: Molecular mechanics restraints for base pairing and base stackingJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2003Stephen C. Harvey Abstract In building and refining nucleic acid structures, it is often desirable to enforce particular base pairing and/or base stacking interactions. Energy-based modeling programs with classical molecular mechanics force fields do not lend themselves to the easy imposition of penalty terms corresponding to such restraints, because the requirement that two bases lie in or near the same plane (pairing) or that they lie in parallel planes (stacking) cannot be easily expressed in terms of traditional interactions involving two atoms (bonds), three atoms (angles), or four atoms (torsions). Here we derive expressions that define a collection of pseudobonds and pseudoangles through which molecular mechanics restraints for base pairing and stacking can be imposed. We have implemented these restraints into the JUMNA package for modeling DNA and RNA structures. JUMNA scripts can specify base pairing with a variety of standard geometries (Watson,Crick, Hoogsteen, wobble, etc.), or with user-defined geometries; they can also specify stacking arrangements. We have also implemented "soft-core" functions to modify van der Waals and electrostatic interactions to avoid steric conflicts in particularly difficult refinements where two backbones need to pass through one another. Test cases are presented to show the utility of the method. The restraints could be adapted for implementation in other molecular mechanics packages. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 1,9, 2003 [source] Molecular aspects on the interaction of protoberberine, benzophenanthridine, and aristolochia group of alkaloids with nucleic acid structures and biological perspectivesMEDICINAL RESEARCH REVIEWS, Issue 5 2007Motilal Maiti Abstract Alkaloids occupy an important position in chemistry and pharmacology. Among the various alkaloids, berberine and coralyne of the protoberberine group, sanguinarine of the benzophenanthridine group, and aristololactam-,- d -glucoside of the aristolochia group have potential to form molecular complexes with nucleic acid structures and have attracted recent attention for their prospective clinical and pharmacological utility. This review highlights (i) the physicochemical properties of these alkaloids under various environmental conditions, (ii) the structure and functional aspects of various forms of deoxyribonucleic acid (DNA) (B-form, Z-form, HL -form, protonated form, and triple helical form) and ribonucleic acid (RNA) (A-form, protonated form, and triple helical form), and (iii) the interaction of these alkaloids with various polymorphic DNA and RNA structures reported by several research groups employing various analytical techniques like absorbance, fluorescence, circular dichroism, and NMR spectroscopy; electrospray ionization mass spectrometry, thermal melting, viscosity, and DNase footprinting as well as molecular modeling and thermodynamic studies to provide detailed binding mechanism at the molecular level for structure,activity relationship. Nucleic acids binding properties of these alkaloids are interpreted in relation to their biological activity. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 5, 649,695, 2007 [source] Building of RNA and DNA double helices into electron densityACTA CRYSTALLOGRAPHICA SECTION D, Issue 6 2008Frantisek Pavelcik A method has been developed that automatically fits double-helical regions into the electron density of nucleic acid structures. Rigid fragments consisting of two Watson,Crick base pairs and three pairs of phosphate groups in the A-type or B-type conformation are positioned into the electron density by phased rotation and translation functions. The position and orientation of the localized double-helical fragments are determined by phased refinement. The method has been tested by building double-helical regions of nine RNA structures of variable crystallographic resolution and polynucleotide length and is available for free use. [source] X-ray-induced debromination of nucleic acids at the Br,K absorption edge and implications for MAD phasingACTA CRYSTALLOGRAPHICA SECTION D, Issue 8 2002E. Ennifar Multi-wavelength anomalous dispersion (MAD) using brominated derivatives is considered a common and convenient technique for solving chemically synthesized nucleic acid structures. Here, it is shown that a relatively moderate X-ray dose (of the order of 5 × 1015,photons,mm,2) can induce sufficient debromination to prevent structure determination. The decrease in bromine occupancy with radiation dose can be accounted for by a simple exponential, with an estimated rate constant at the absorption-peak wavelength, 7.4,(0.8),MGy, that is not significantly different from its value at the absorption-edge wavelength, 9.2,(2.6),MGy (the given e.s.d.s assess the relative closeness of the two values, not their absolute accuracy, which is probably worse). Chemically, these results (and others) are consistent with bromine cleavage resulting from direct photodissociation and/or from the action of free electrons, rather than from the action of hydroxyl radicals originating from water dissociation. The free bromine species (Br,) diffuse too quickly, even in amorphous ice around 100,K, to allow the determination of a diffusion coefficient. From a practical point of view, it is suggested that a single data collection with a crystal consisting of iodinated instead of brominated derivatives could provide both anomalous scattering and SIR phase information by the progressive cleavage of iodine. [source] Pyrazine Arotinoids with Inverse Agonist Activities on the Retinoid and Rexinoid ReceptorsCHEMBIOCHEM, Issue 7 2009José García Abstract RAR and RXR agonists: A collection of pyrazine-based RAR/RXR ligands were prepared by a series of palladium catalyzed cross-coupling reactions and characterized. Structure,activity relationships were elucidated. Retinoic acid receptor (RAR) ,/,-subtype-selective and retinoid X receptor (RXR) inverse agonist activities are described for pyrazine acrylic acid arotinoid, 14,d. Heterocyclic arotinoids derived from central-region dihalogenated pyrazine scaffolds have been synthesized by consecutive halogen and/or position-selective palladium-catalyzed cross-coupling reactions. Pyrazines were further functionalized as alkyl ethers or methylamines prior to the last Pd-catalyzed reactions. Transient transactivation studies with the retinoic acid receptor (RAR) ,, ,, and , subtypes and with retinoid X receptor (RXR) , revealed distinct agonist, antagonist, and inverse agonist activities for these compounds. Of interest are the RAR,,,-selective inverse agonists with pyrazine acrylic acid structures, in particular 14,c, which is RAR,-selective, and 14,d, a pan-RAR/RXR inverse agonist with more affinity for the RAR subtypes that enhance the interaction of RAR with cognate corepressors. 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