Synthesis, biochemical, and biological evaluation of C2 linkage derivatives of amino sugars, inhibitors of glucokinase from Trypanosoma cruzi.

Eighteen amino sugar analogues were screened against Trypanosoma cruzi glucokinase (TcGlcK), a potential drug-target of the protozoan parasite in order to assess for viable enzyme inhibition. The analogues were divided into three amino sugar scaffolds that included d-glucosamine (d-GlcN), d-mannosamine (d-ManN), and d-galactosamine (d-GalN); moreover, all but one of these compounds were novel. TcGlcK is an important metabolic enzyme that has a role in producing G6P for glycolysis and the pentose phosphate pathway (PPP).

Metabolomic Profile of Allantoic and Amniotic Fluid in Late-term Gestational Mares Characterized by H-nuclear Magnetic Resonance Spectroscopy.

The amniotic and allantoic fluid compartments in the mare serve essential roles throughout pregnancy and parturition. Although the global metabolomic profile of amniotic fluid in women has been extensively characterized, current data for equine fetal fluids are limited. Therefore, the goal of this study was to characterize the global metabolomic profile of equine allantoic and amniotic fluid through nuclear magnetic resonance spectroscopy.

Plasma metabolomic profiling of healthy pregnant mares and mares with experimentally induced placentitis.

Background: Metabolomics may represent an avenue for diagnosis of equine ascending placentitis.

Objectives: To characterise the plasma metabolomic profile in healthy mares and mares with induced ascending placentitis, with the goal of identifying metabolites with potential clinical value for early diagnosis of placentitis.

Study Design: Controlled in vivo experiment.

NMR Metabolomic Analysis of Skeletal Muscle, Heart, and Liver of Hatchling Loggerhead Sea Turtles () Experimentally Exposed to Crude Oil and/or Corexit.

We used nuclear magnetic spectroscopy (NMR) to evaluate the metabolic impacts of crude oil, Corexit 5900A, a dispersant, and a crude oil Corexit 5900A mixture exposure on skeletal muscle, heart, and liver physiology of hatchling loggerhead sea turtles (). Tissue samples were obtained from 22 seven-day-old hatchlings after a four day cutaneous exposure to environmentally relevant concentrations of crude oil, Corexit 5900A, a combination of crude oil and Corexit 9500A, or a seawater control. We identified 38 metabolites in the aqueous extracts of the liver, and 30 metabolites in both the skeletal and heart muscle aqueous extracts, including organic acids/osmolytes, energy compounds, amino acids, ketone bodies, nucleosides, and nucleotides.

Dynamics of dehaloperoxidase-hemoglobin A derived from NMR relaxation spectroscopy and molecular dynamics simulation.

Dehaloperoxidase-hemoglobin is the first hemoglobin identified with biologically-relevant oxidative functions, which include peroxidase, peroxygenase and oxidase activities. Herein we report a study of the protein backbone dynamics of DHP using heteronuclear NMR relaxation methods and molecular dynamics (MD) simulations to address the role of protein dynamics in switching from one function to another. The results show that DHP's backbone helical regions and turns have average order parameters of S = 0.

Evaluation of physical and chemical properties and their interactions in fat, oil, and grease (FOG) deposits.

Fat, oil and grease (FOG) blockages in sewer systems are a substantial problem in the United States. It has been estimated that over 50% of sewer overflows are a result of FOG blockages. In this work, a thorough laboratory study was undertaken to examine key variables that contribute to FOG deposit formation under controlled conditions.

Structure-based approach to the identification of a novel group of selective glucosamine analogue inhibitors of Trypanosoma cruzi glucokinase.

Glucokinase and hexokinase from pathogenic protozoa Trypanosoma cruzi are potential drug targets for antiparasitic chemotherapy of Chagas' disease. These glucose kinases phosphorylate d-glucose with co-substrate ATP and yield glucose 6-phosphate and are involved in essential metabolic pathways, such as glycolysis and the pentose phosphate pathway. An inhibitor class was conceived that is selective for T.

Chemical changes during anaerobic decomposition of hardwood, softwood, and old newsprint under mesophilic and thermophilic conditions.

The anaerobic decomposition of plant biomass is an important aspect of global organic carbon cycling. While the anaerobic metabolism of cellulose and hemicelluloses to methane and carbon dioxide are well-understood, evidence for the initial stages of lignin decomposition is fragmentary. The objective of this study was to look for evidence of chemical transformations of lignin in woody tissues [hardwood (HW), softwood (SW), and old newsprint (ONP)] after anaerobic decomposition using Klason and acid-soluble lignin, CuO oxidation, and 2D NMR.

Nonphotochemical base-catalyzed hydroxylation of 2,6-dichloroquinone by H2O2 occurs by a radical mechanism.

Kinetic and structural studies have shown that peroxidases are capable of the oxidation of 2,4,6-trichlorophenol (2,4,6-TCP) to 2,6-dichloro-1,4-benzoquinone (2,6-DCQ). Further reactions of 2,6-DCQ in the presence of H(2)O(2) and OH(-) yield 2,6-dichloro-3-hydroxy-1,4-benzoquinone (2,6-DCQOH). The reactions of 2,6-DCQ have been monitored spectroscopically [UV-visible and electron spin resonance (ESR)] and chromatographically.

Functional consequences of the creation of an Asp-His-Fe triad in a 3/3 globin.

The proximal side of dehaloperoxidase-hemoglobin A (DHP A) from Amphitrite ornata has been modified via site-directed mutagenesis of methionine 86 into aspartate (M86D) to introduce an Asp-His-Fe triad charge relay. X-ray crystallographic structure determination of the metcyano forms of M86D [Protein Data Bank (PDB) entry 3MYN ] and M86E (PDB entry 3MYM ) mutants reveal the structural origins of a stable catalytic triad in DHP A. A decrease in the rate of H(2)O(2) activation as well as a lowered reduction potential versus that of the wild-type enzyme was observed in M86D.

Photobactericidal porphyrin-cellulose nanocrystals: synthesis, characterization, and antimicrobial properties.

Adherence and survival of pathogenic bacteria on surfaces leading to concomitant transmission to new hosts significantly contributes to the proliferation of pathogens, which in turn considerably increases the threat to human health, particularly by antibiotic-resistant bacteria. Consequently, more research into effective surface disinfection and alternative materials (fabrics, plastics, or coatings) with antimicrobial and other bioactive characteristics is desirable. This report describes the synthesis and characterization of cellulose nanocrystals that were surface-modified with a cationic porphyrin.

Quantification of lignin-carbohydrate linkages with high-resolution NMR spectroscopy.

A quantitative approach to characterize lignin-carbohydrate complex (LCC) linkages using a combination of quantitative ¹³C NMR and HSQC 2D NMR techniques has been developed. Crude milled wood lignin (MWLc), LCC extracted from MWLc with acetic acid (LCC-AcOH) and cellulolytic enzyme lignin (CEL) preparations were isolated from loblolly pine (Pinus taeda) and white birch (Betula pendula) woods and characterized using this methodology on a routine 300 MHz NMR spectrometer and on a 950 MHz spectrometer equipped with a cryogenic probe. Structural variations in the pine and birch LCC preparations of different types (MWL, CEL and LCC-AcOH) were elucidated.

Synthesis, NMR characterization and divergent biological actions of 2'-hydroxy-ceramide/dihydroceramide stereoisomers in MCF7 cells.

A straightforward method for the simultaneous preparation of (2S,3R,2'R)- and (2S,3R,2'S)-2'-hydroxy-ceramides (2'-OHCer) from (2S,3R)-sphingosine acetonide precursors and racemic mixtures of 2-hydroxy fatty acids (2-OHFAs) is described. The obtained 2'-OH-C4-, -C6-, -C12-, -C16-Cer and 2'-OH-C6-dhCer pairs of diastereoisomers were characterized thoroughly by TLC, MS, NMR, and optical rotation. Dynamic and multidimensional NMR studies provided evidence that polar interfaces of 2'-OHCers are extended and more rigid than observed for the corresponding non-hydroxylated analogs.

Different modes of binding of mono-, di-, and trihalogenated phenols to the hemoglobin dehaloperoxidase from Amphitrite ornata.

The hemoglobin dehaloperoxidase (DHP), found in the coelom of the terebellid polychaete Amphitrite ornata, is a dual-function protein that has the characteristics of both hemoglobins and peroxidases. In addition to oxygen transport function, DHP readily oxidizes halogenated phenols in the presence of hydrogen peroxide. The peroxidase activity of DHP is high relative to that of wild-type myoglobin or hemoglobin, but the most definitive difference in DHP is a well-defined substrate-binding site in the distal pocket, which was reported for 4-iodophenol in the X-ray crystal structure of DHP.

NMR studies of the inclusion complex of cloprostenol sodium salt with beta-cyclodextrin in aqueous solution.

Purpose: Cloprostenol sodium salt (referred as cloprostenol) may be used for the synchronization of estrous cycles in farm animal species. Cyclodextrins (CDs) have potential as drug delivery systems through the formation of inclusion complexes between CDs and drugs. This is the first study of the inclusion complex of cloprostenol with beta-cyclodextrin (beta-CD) in aqueous solution using NMR and 3D molecular dynamics simulations.

Tailoring structure-function and targeting properties of ceramides by site-specific cationization.

In the course of our studies on compartment-specific lipid-mediated cell regulation, we identified an intimate connection between ceramides (Cers) and the mitochondria-dependent death-signaling pathways. Here, we report on a new class of cationic Cer mimics, dubbed ceramidoids, designed to act as organelle-targeted sphingolipids (SPLs), based on conjugates of Cer and dihydroceramide (dhCer) with pyridinium salts (CCPS and dhCCPS, respectively). Ceramidoids having the pyridinium salt unit (PSU) placed internally (alpha and gamma- CCPS) or as a tether (omega-CCPS) in the N-acyl moiety were prepared by N-acylation of sphingoid bases with different omega-bromo acids or pyridine carboxylic acid chlorides following capping with respective pyridines or alkyl bromides.

Structural study of irregular amino acid sequences in the heavy chain of Bombyx mori silk fibroin.

Recently, genetic studies have revealed the entire amino acid sequence of Bombyx mori silk fibroin. It is known from X-ray diffraction studies that the beta-sheet crystalline structure (silk II) of fibroin is composed of hexaamino acid sequences of GAGAGS. However, in the heavy chain of B.

Structural characterization of an intermolecular RNA-RNA interaction involved in the transcription regulation element of a bipartite plant virus.

The 34-nucleotide trans-activator (TA) located within the RNA-2 of Red clover necrotic mosaic virus folds into a simple hairpin. The eight-nucleotide TA loop base pairs with eight complementary nucleotides in the TA binding sequence (TABS) of the capsid protein subgenomic promoter on RNA-1 and trans-activates subgenomic RNA synthesis. Short synthetic oligoribonucleotide mimics of the RNA-1 TABS and the RNA-2 TA form a weak 1:1 bimolecular complex in vitro with a K(a) of 5.

Comparative studies on the delignification of pine kraft-anthraquinone pulp with hydrogen peroxide by binucleus Mn(IV) complex catalysis.

Pine kraft-anthraquinone (kraft-AQ) pulp was bleached in alkaline solution with hydrogen peroxide catalyzed by either [L(1)Mn(IV)(micro-O)(3)Mn(IV)L(1)](PF(6))(2)] (C1) or [LMn(IV)(2)(micro-O)(3)] (ClO(4))(2) (C2) at 60 and 80 degrees C for 120 min with a catalyst charge of 10 ppm on pulp. The resulting bleached pulp was hydrolyzed with cellulase to obtain insoluble and soluble residual lignins. The alkaline bleaching effluents were acidified to precipitate alkaline-soluble lignins.

Elucidation of the structures of residual and dissolved pine kraft lignins using an HMQC NMR technique.

Comparative studies on the structures of residual and dissolved lignins isolated from pine kraft pulp and pulping liquor have been undertaken using the (1)H-(13)C HMQC NMR technique, GPC, and sugar analysis to elucidate the reaction mechanisms in kraft pulping and the lignin reactivity. A modified procedure for the isolation of enzymatic residual lignins has resulted in an appreciable decrease in protein contaminants in the residual lignin preparations (N content < 0.2%).

Reaction mechanisms in delignification of pine Kraft-AQ pulp with hydrogen peroxide using Mn(IV)-Me4DTNE as catalyst.

Pine Kraft-AQ pulp was bleached with hydrogen peroxide catalyzed by [LMn(IV)(2) (mu-O)(3)](ClO(4))(2) at 80 degrees C for 120 min under optimum reaction conditions. The resulting bleached pulp was hydrolyzed with cellulase to obtain insoluble and soluble residual lignins. The alkaline effluent from the bleaching was acidified to precipitate alkaline soluble lignin.

Xanosporic acid, an intermediate in bacterial degradation of the fungal phototoxin cercosporin.

The red fungal perylenequinone phototoxin cercosporin is oxidized by Xanthomonas campestris pv zinniae to a non-toxic, unstable green metabolite xanosporic acid, identified via its lactone as 1,12-bis(2'R-hydroxypropyl)-4,9-dihydroxy-6,7-methylenedioxy-11-methoxy-3-oxaperylen-10H-10-one-2-carboxylic acid. Xanosporolactone was isolated in approximately 2:1 ratio of M:P atropisomers.

13C-NMR study of hypoglycemia-induced glycolytic changes in embryonic mouse heart.

Background: Glucose metabolites can be detected in embryonic mouse tissues using 13C-NMR spectroscopy. The advantage of this method is in its chemical specificity and the ability to follow metabolic changes.

Methods: In this study, CD-1 mice were mated and embryos excised on gestational day (GD) 10.