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Chemical Synthesis (chemical + synthesis)
Kinds of Chemical Synthesis Selected AbstractsModular Microreaction Systems for Homogeneously and Heterogeneously Catalyzed Chemical SynthesisHELVETICA CHIMICA ACTA, Issue 1 2005Daniel Until now, microreaction devices designed for a specific type of reaction were used mainly for highly exothermic, very fast reactions. Described is a modular microreaction system and its application to representative homogeneous and heterogeneous reactions important in organic synthesis. The modular microreaction system allows continuous flow processes to be optimized and employed effectively in the chemical laboratory. The modular microreaction systems proved also versatile for syntheses requiring moderate reaction times, thus extending their application to a large fraction of organic reactions. The use of the modular and cleanable microreaction systems to rapidly develop optimized reaction conditions provides an excellent basis for the development of many chemical transformations scalable from milligram to ton production quantities. [source] Chemical Synthesis of Nanocrystalline Strontium Bismuth Tantalate Powders Using Tantalum,Tartarate ComplexJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 2 2006Asit Baran Panda Nanocrystalline strontium bismuth tantalate (SrBi2Ta2O9; SBT) powders have been synthesized through complete dehydration of an aqueous solution mixture of tantalum tartarate, strontium salt of ethylenediaminetetraacetic acid, and bismuth,triethanolamine complex. Single-step calcination of the fluffy, mesoporous, carbonaceous dehydrated precursor mass at 700°C/2 h results in nanosized SBT powders, with average particle size ,15 nm. When palletized and sintered at 950°C/4 h these powders show a relative density of 97.6% of theoretical value, and a maximum dielectric constant value of 1387 at Tc (Curie temperature)=279°C, when measured at 100 kHz. [source] Chemical Synthesis of Triple-Labelled Three-Helix Bundle Binding Proteins for Specific Fluorescent Detection of Unlabelled ProteinCHEMBIOCHEM, Issue 6 2005Torun Engfeldt Abstract Site-specifically triple-labelled three-helix bundle affinity proteins (affibody molecules) have been produced by total chemical synthesis. The 58 aa affinity proteins were assembled on an automated peptide synthesizer, followed by manual on-resin incorporation of three different reporter groups. An orthogonal protection strategy was developed for the site-specific introduction of 5-(2-aminethylamino)-1-naphthalenesulfonic acid (EDANS) and 6-(7-nitrobenzofurazan-4-ylamino)-hexanoic acid (NBDX), constituting a donor/acceptor pair for fluorescence resonance energy transfer (FRET), and a biotin moiety, used for surface immobilization. Circular dichroism and biosensor studies of the synthetic proteins and their recombinant counterparts revealed that the synthetic proteins were folded and retained their binding specificities. The biotin-conjugated protein could be immobilized onto a streptavidin surface without loss of activity. The synthetic, doubly fluorescent-labelled affinity proteins were shown to function as fluorescent biosensors in an assay for the specific detection of unlabelled human IgG and IgA. [source] ChemInform Abstract: A Multigram Chemical Synthesis of the ,-Secretase Inhibitor LY411575 and Its Diastereoisomers.CHEMINFORM, Issue 10 2008Abdul H. Fauq Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Wet Chemical Synthesis of Pure LiNbO3 Powders from Simple Niobium Oxide Nb2O5.CHEMINFORM, Issue 9 2007Meinan Liu Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Silver(I) Fluoride and Related Compounds in Chemical Synthesis.CHEMINFORM, Issue 5 2003Wieland Tyrra Abstract For Abstract see ChemInform Abstract in Full Text. [source] ChemInform Abstract: Palladium-Catalyzed Reactions for Fine Chemical Synthesis.CHEMINFORM, Issue 50 2001Part 21. Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: Chemical Synthesis of Tin Oxide-Based Materials for Li-Ion Battery Anodes.CHEMINFORM, Issue 10 2001Jin Yong Kim Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] New Uses for the Burgess Reagent in Chemical Synthesis: Methods for the Facile and Stereoselective Formation of Sulfamidates, Glycosylamines, and SulfamidesCHEMISTRY - A EUROPEAN JOURNAL, Issue 22 2004K. C. Nicolaou Prof. Abstract Although the Burgess reagent (methoxycarbonylsulfamoyltriethylammonium hydroxide, inner salt) has found significant use in chemical synthesis as a dehydrating agent, almost no work has been directed towards its potential in other synthetic applications. As this article will detail, we have found that the Burgess reagent is remarkably effective at accomplishing a number of non-dehydrative synthetic tasks when applied to appropriate substrates, such as the formation of sulfamidates from 1,2-diols or epoxyalcohols, ,- and ,-glycosylamines from carbohydrates, and cyclic sulfamides from 1,2-aminoalcohols. Beyond delineating the power of these new reaction manifolds, we also describe the construction of a group of alternative Burgess-type reagents that extends the scope of these new reactions even further. [source] Molecular Design and Chemical Synthesis of a Highly Potent Epothilone,CHEMMEDCHEM, Issue 1 2006C. Nicolaou Prof. De,novo designed and synthesized methylthiopyrazole epothilone,B boasts a stunning biological profile against tumor cells, with activity at sub-nanomolar (IC50=0.06,nm) concentrations. [source] Metabolism of Deuterated erythro -Dihydroxy Fatty Acids in Saccharomyces cerevisiae: Enantioselective Formation and Characterization of HydroxylactonesHELVETICA CHIMICA ACTA, Issue 6 2008Leif-A. Abstract Epoxides of fatty acids are hydrolyzed by epoxide hydrolases (EHs) into dihydroxy fatty acids which are of particular interest in the mammalian leukotriene pathway. In the present report, the analysis of the configuration of dihydroxy fatty acids via their respective hydroxylactones is described. In addition, the biotransformation of (±)- erythro -7,8- and -3,4-dihydroxy fatty acids in the yeast Saccharomyces cerevisiae was characterized by GC/EI-MS analysis. Biotransformation of chemically synthesized (±)- erythro -7,8-dihydroxy(7,8- 2H2)tetradecanoic acid ((±)- erythro - 1) in the yeast S. cerevisiae resulted in the formation of 5,6-dihydroxy(5,6- 2H2)dodecanoic acid (6), which was lactonized into (5S,6R)-6-hydroxy(5,6- 2H2)dodecano-5-lactone ((5S,6R)- 4) with 86% ee and into erythro -5-hydroxy(5,6- 2H2)dodecano-6-lactone (erythro - 8). Additionally, the , -ketols 7-hydroxy-8-oxo(7- 2H1)tetradecanoic acid (9a) and 8-hydroxy-7-oxo(8- 2H1)tetradecanoic acid (9b) were detected as intermediates. Further metabolism of 6 led to 3,4-dihydroxy(3,4- 2H2)decanoic acid (2) which was lactonized into 3-hydroxy(3,4- 2H2)decano-4-lactone (5) with (3R,4S)- 5=88% ee. Chemical synthesis and incubation of (±)- erythro -3,4-dihydroxy(3,4- 2H2)decanoic acid ((±)- erythro - 2) in yeast led to (3S,4R)- 5 with 10% ee. No decano-4-lactone was formed from the precursors 1 or 2 by yeast. The enantiomers (3S,4R)- and (3R,4S)-3,4-dihydroxy(3- 2H1)nonanoic acid ((3S,4R)- and (3R,4S)- 3) were chemically synthesized and comparably degraded by yeast without formation of nonano-4-lactone. The major products of the transformation of (3S,4R)- and (3R,4S)- 3 were (3S,4R)- and (3R,4S)-3-hydroxy(3- 2H1)nonano-4-lactones ((3S,4R)- and (3R,4S)- 7), respectively. The enantiomers of the hydroxylactones 4, 5, and 7 were chemically synthesized and their GC-elution sequence on Lipodex®E chiral phase was determined. [source] Chemical synthesis and biosynthesis of the cyclotide family of circular proteinsIUBMB LIFE, Issue 9 2006Sunithi Gunasekera Abstract Cyclotides are a recently discovered class of proteins that have a characteristic head-to-tail cyclized backbone stabilized by a knotted arrangement of three disulfide bonds. They are exceptionally resistant to chemical, enzymatic and thermal treatments because of their unique structural scaffold. Cyclotides have a range of bio-activities, including uterotonic, anti-HIV, anti-bacterial and cytotoxic activity but their insecticidal properties suggest that their natural physiological role is in plant defense. They are genetically encoded as linear precursors and subsequently processed to produce mature cyclic peptides but the mechanism by which this occurs remains unknown. Currently most cyclotides are obtained via direct extraction from plants in the Rubiaceae and Violaceae families. To facilitate the screening of cyclotides for structure-activity studies and to exploit them in drug design or agricultural applications a convenient route for the synthesis of cyclotides is vital. In this review the current chemical, recombinant and biosynthetic routes to the production of cyclotides are discussed. iubmb Life, 58: 515-524, 2006 [source] Generating heat from conducting polypyrrole-coated PET fabricsADVANCES IN POLYMER TECHNOLOGY, Issue 3 2005Akif Kaynak Abstract Heating effects in polypyrrole-coated polyethyleneterephthalate (PET)-Lycra® fabrics were studied. Chemical synthesis was employed to coat the PET fabrics by polypyrrole using ferric chloride as oxidant and antraquinone- 2-sulfonic acid (AQSA) and naphthalene sulfonic acid (NSA) as dopants. The coated fabrics exhibited reasonable electrical stability, possessed high electrical conductivity, and were effective in heat generation. Surface resistance of polypyrrole-coated fabrics ranged from approximately 150 to 500 ,/square. Different connections between conductive fabrics and the power source were examined. When subjected to a constant voltage of 24 V, the current transmitted through the fabric decreased about 10% in 72 h. An increase in resistance of conductive fabrics subjected to constant voltage was observed. © 2005 Wiley Periodicals, Inc. Adv Polym Techn 24: 194,207, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.20040 [source] Biosynthesis of peptide fragments of eukaryotic GPCRs in Escherichia coli by directing expression into inclusion bodiesJOURNAL OF PEPTIDE SCIENCE, Issue 5 2010Leah S. Cohen Abstract Biosynthesis of peptides in heterologous systems is often a prerequisite to biophysical analyses. Large amounts of peptides, in particular portions of membrane proteins, are needed to optimize conditions for secondary and tertiary structure analysis. Chemical synthesis of these peptides is limited by their high hydrophobicity and also due to the need to incorporate isotopic labels for high resolution NMR analysis. In this protocol, we describe a method for the heterologous expression and purification of unlabeled and isotopically labeled peptide fragments of Ste2p, an integral membrane G protein-coupled receptor. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. [source] Chemical synthesis and electric properties of the conducting copolymer of aniline and o -aminophenolJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 23 2007Jing Zhang Abstract A copolymer, poly(aniline- co-o -aminophenol), was prepared chemically by using ammonium peroxydisulfate as an oxidant. The monomer concentration ratio of o -aminophenol to aniline strongly influences the copolymerization rate and properties of the copolymer. The optimum composition of a mixture for the chemical copolymerization consisted of 0.3 M aniline, 0.021 M o -aminophenol, 0.42 M ammonium peroxydisulfate, and 2 M H2SO4. The result of cyclic voltammograms in a potential region of ,0.20 to 0.80 V (vs.SCE) indicates that the electrochemical activity of the copolymer prepared under the optimum condition is similar to that of polyaniline in more acid solutions. However, the copolymer still holds the good electrochemical activity until pH 11.0. Therefore, the pH dependence of the electrochemical property of the copolymer is improved, compared with poly(aniline- co-o -aminophenol) prepared electrochemically, and is much better than that of polyaniline. The spectra of IR and 1H NMR confirm that o -aminophenol units are included in the copolymer chain, which play a key role in extending the usable pH region of the copolymer. The visible spectra of the copolymers show that a high concentration ratio of o -aminophenol to aniline in a mixture inhibits the chain growth. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5573,5582, 2007 [source] Chemical synthesis and biotinylation of the thrombospondin domain TSR2PROTEIN SCIENCE, Issue 5 2009Theresa K. Tiefenbrunn Abstract The type 1 repeat domain from thrombospondin has potent antiangiogenic activity and a structurally interesting fold, making it an attractive target for protein engineering. Chemical synthesis is an attractive approach for studying protein domains because it enables the use of unnatural amino acids for site-specific labeling and detailed structure-function analysis. Here, we demonstrate the first total chemical synthesis of the thrombospondin type 1 repeat domain by native chemical ligation. In addition to the natural domain, five sites for side chain modification were evaluated and two were found to be compatible with oxidative folding. Several challenges were encountered during peptide synthesis due to the functional complexity of the domain. These challenges were overcome by the use of new solid supports, scavengers, and the testing of multiple ligation sites. We also describe an unusual sequence-specific protecting group migration observed during cleavage resulting in +90 Da and +194 Da adducts. Synthetic access to this domain enables the synthesis of a number of variants that can be used to further our understanding of the biochemical interaction network of thrombospondin and provide insight into the structure and function of this important antitumorogenic protein domain. [source] Distribution of piperitone oxide stereoisomers in Mentha and Micromeria species and their chemical synthesesFLAVOUR AND FRAGRANCE JOURNAL, Issue 4 2007Olga Larkov Abstract Chiral GC,MS analyses of natural and synthetic trans- and cis- piperitone oxide were performed on an Rt- ,DEX-sm capillary column in order to clarify the stereochemistry of their enantiomeric forms. Only enantiomerically pure laevo-rotatory piperitone oxides, (1S,2S,4S)- trans- piperitone oxide and (1S,2S,4R)- cis- piperitone oxide, were detected by chiral analyses of Micromeria fruticosa (L.) Druce and Mentha longifolia L. The occurrence of the cis - and trans -piperitone oxides was dependent on the population of the species. In all cases (1S,2S,4S)- trans- piperitone oxide was detected together with (4S)-piperitone, while (1S,2S,4R)- cis- piperitone oxide was detected together with (4R)-piperitone in the plants analysed. The four stereoisomers of trans - and cis -piperitone oxide were obtained by alkaline epoxidation of both (4R)- and (4S)-piperitone. The formation of the 1,2-epoxide can take place on either side of the 1,4-substituted six-membered ring. Racemization at C4 was observed under alkaline epoxidation reaction conditions due to keto-enol tautomerism. Copyright © 2007 John Wiley & Sons, Ltd. [source] Influence of carbohydrates on stability of papain in aqueous tetrahydrofuran mixtureJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 1 2009András Szabó Abstract BACKGROUND: The use of enzymes in organic solvents has extended the scale of their practical applications. Papain has been widely used in chemical syntheses because of its broad substrate specificity. The aim of the present study was to improve the stability of papain in aqueous tetrahydrofuran (THF) by using different saccharides. The effects of these carbohydrates on the structure of papain were followed by means of circular dichroism (CD) and fluorescence spectroscopic measurements. RESULTS: In contrast with most organic solvents, 60% (i.e. 600 mL L,1) THF practically inactivated the enzyme within 30 min. Sugars protected papain from THF-induced inactivation in the sequence D -ribose > D -fructose > D -glucose > D -saccharose > D -raffinose. Ribose at 1.6 mol L,1 proved the most effective stabiliser: in 60% THF in the presence of ribose, papain preserved about 55% of its initial activity after 2 h. Fluorescence and near-UV CD spectroscopic measurements revealed local changes in the papain conformation. With decrease in the free amino group content of the enzyme, protein-carbohydrate interactions (Schiff base formation) were detected. CONCLUSION: These results demonstrate that the catalytic activity and stability of papain may be increased in aqueous THF by using different carbohydrates, when a more compact structure of the enzyme is formed. Copyright © 2008 Society of Chemical Industry [source] Biofilms,new designer biocatalysts for robust chemical syntheses?BIOTECHNOLOGY & BIOENGINEERING, Issue 6 2007Article first published online: 24 OCT 200 No abstract is available for this article. [source] Optimization of a Process Synthesis Superstructure Using an Ant Colony AlgorithmCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 3 2008B. Raeesi Abstract The optimization of chemical syntheses based on superstructure modeling is a perfect way for achieving the optimal plant design. However, the combinatorial optimization problem arising from this method is very difficult to solve, particularly for the entire plant. Relevant literature has focused on the use of mathematical programming approaches. Some research has also been conducted based on meta-heuristic algorithms. In this paper, two approaches are presented to optimize process synthesis superstructure. Firstly, mathematical formulation of a superstructure model is presented. Then, an ant colony algorithm is proposed for solving this nonlinear combinatorial problem. In order to ensure that all the constraints are satisfied, an adaptive, feasible bound for each variable is defined to limit the search space. Adaptation of these bounds is executed by the suggested bound updating rule. Finally, the capability of the proposed algorithm is compared with the conventional Branch and Bound method by a case study. [source] Analysis of oxycodol and noroxycodol stereoisomers in biological samples by capillary electrophoresisELECTROPHORESIS, Issue 10 2005Andrea Baldacci Abstract A capillary electrophoresis (CE) method for the separation of the diastereoisomers of 6-oxycodol (6OCOL) and nor-6-oxycodol (N6OCOL), the 6-keto-reduced metabolites of oxycodone (OCOD) and noroxycodone (NOCOD), respectively, is reported and employed to assess the stereoselectivity of these metabolic steps in vivo, in vitro, and in chemical synthesis. CE in an untreated fused-silica capillary with acidic buffers containing 2-hydroxypropyl-,-cyclodextrin, randomly sulfated ,-cyclodextrin, or single isomer heptakis(2,3-diacetyl-6-sulfato)-,-cyclodextrin (HDAS-,-CD) is shown to permit the simultaneous separation of the stereoisomers of 6OCOL and N6OCOL. A 100 mM phosphate buffer of pH 2.0 containing 2.05% w/v HDAS-,-CD provides a medium for rapid analysis and unambiguous identification of these stereoisomers in solid-phase extracts of (i) urines stemming from patients under pharmacotherapy with OCOD, (ii) incubations of OCOD and NOCOD with human liver cytosol and the human liver S9 fraction, and (iii) after chemical synthesis from OCOD and NOCOD using NaBH4. In all cases, ,-N6OCOL is shown to be the predominant stereoisomer of N6OCOL. For 6OCOL, the same is true for in vitro formation and for chemical synthesis. In urine, however, ,-6OCOL is observed to be excreted in a higher amount than ,-6OCOL. For the urinary ,-/,-isomer ratio of 6OCOL and N6OCOL, there are no differences between the data obtained for nonhydrolyzed and enzymatically hydrolyzed urines. The data document the stereoselectivity of the 6-keto-reduction of OCOD and NOCOD in man. [source] Microautosamplers for discrete sample injection and dispensationELECTROPHORESIS, Issue 9 2005Chun-Wei Huang Abstract Microfluidic systems show considerable potential for use in the continuous reaction and analysis of biosamples for various applications, such as drug screening and chemical synthesis. Typically, microfluidic chips are externally connected with large-scale autosamplers to inject specific volumes of discrete samples in the continuous monitoring and analysis of multiple samples. This paper presents a novel microelectromechanical system (MEMS)-based autosampler capable of performing the discrete injection and dispensation of variable-volume samples. This microdevice can be integrated with other microfluidic devices to facilitate the continuous monitoring and analysis of multiple biosamples. By means of electroosmotic focusing and switching controlled by the direct application of electric sources on specific fluid reservoirs, a precise sample volume can be injected into the specified outlet port. Fluorescence dye images verify the performance of the developed device. An injection-and-washing scheme is developed to prevent cross-contamination during the continuous injection of different samples. This approach renders feasible the injection of several discrete samples using a single microchip. Compared to its large-scale counterparts, the developed microautosampler is compact in size, has low fabrication costs, is straightforward to control, and most importantly, is readily integrated with other microfluidic devices (e.g., microcapillary electrophoresis chips) to form a microfluidic system capable of the continuous monitoring and analysis of bioreactions. The proposed microautosampler could be promising towards realizing the micrototal analysis system (,-TAS) concept. [source] Assessment of the sensitivity of the computational programs DEREK, TOPKAT, and MCASE in the prediction of the genotoxicity of pharmaceutical moleculesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2004Ronald D. Snyder Abstract Computational models are currently being used by regulatory agencies and within the pharmaceutical industry to predict the mutagenic potential of new chemical entities. These models rely heavily, although not exclusively, on bacterial mutagenicity data of nonpharmaceutical-type molecules as the primary knowledge base. To what extent, if any, this has limited the ability of these programs to predict genotoxicity of pharmaceuticals is not clear. In order to address this question, a panel of 394 marketed pharmaceuticals with Ames Salmonella reversion assay and other genetic toxicology findings was extracted from the 2000,2002 Physicians' Desk Reference and evaluated using MCASE, TOPKAT, and DEREK, the three most commonly used computational databases. These evaluations indicate a generally poor sensitivity of all systems for predicting Ames positivity (43.4,51.9% sensitivity) and even poorer sensitivity in prediction of other genotoxicities (e.g., in vitro cytogenetics positive; 21.3,31.9%). As might be expected, all three programs were more highly predictive for molecules containing carcinogenicity structural alerts (i.e., the so-called Ashby alerts; 61% ± 14% sensitivity) than for those without such alerts (12% ± 6% sensitivity). Taking all genotoxicity assay findings into consideration, there were 84 instances in which positive genotoxicity results could not be explained in terms of structural alerts, suggesting the possibility of alternative mechanisms of genotoxicity not relating to covalent drug-DNA interaction. These observations suggest that the current computational systems when applied in a traditional global sense do not provide sufficient predictivity of bacterial mutagenicity (and are even less accurate at predicting genotoxicity in tests other than the Salmonella reversion assay) to be of significant value in routine drug safety applications. This relative inability of all three programs to predict the genotoxicity of drugs not carrying obvious DNA-reactive moieties is discussed with respect to the nature of the drugs whose positive responses were not predicted and to expectations of improving the predictivity of these programs. Limitations are primarily a consequence of incomplete understanding of the fundamental genotoxic mechanisms of nonstructurally alerting drugs rather than inherent deficiencies in the computational programs. Irrespective of their predictive power, however, these programs are valuable repositories of structure-activity relationship mutagenicity data that can be useful in directing chemical synthesis in early drug discovery. Environ. Mol. Mutagen. 43:143,158, 2004. © 2004 Wiley-Liss, Inc. [source] An assay system for the detection of phospholipase C activityEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 10 2003Markus Durban Abstract Phospholipase C (PLC, EC 3.1.4.3) enzymes specifically hydrolyze the C-O-P-bond in phospholipids, yielding sn -1, 2(2, 3)-diglycerides and a phosphate residue bearing the corresponding head group. Biochemical characterization of PLC requires methods for determination of activity. During characterization and purification, proteins are separated by polyacrylamide gel electrophoresis (PAGE). For direct identification and visualization of PLC, a new assay for activity staining in native and renatured SDS-PAGE is described. Incubation of a gel containing an active PLC in the presence of ,-naphthylphosphorylcholine leads to ,-naphthol formation. This reacts with the diazonium salt Fast Red, forming a red dye which allows clear determination of PLC purity, molecular weight and substrate specificity. The assay was verified using commercially available PC-PLC and new PC-PLC-producing Bacillus cereus strains. The substrate ,-NPC was prepared by chemical synthesis at an overall yield of 12%. [source] The First Mimetic of the Transketolase ReactionEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 5 2006Mark E. B. Smith Abstract Although the biocatalytic formation of acyclic ,,,,-dihydroxy ketones by transketolase is well documented in the literature, there is currently no one-pot chemical synthesis of these dihydroxy ketones available. Here, we report preliminary results of an atom-efficient one-pot synthesis of ,,,,-dihydroxy ketones in water by a mimic of the transketolase reaction. The formation of a quaternary ammonium enolate is postulated in this tertiary-amine-mediated carbon,carbon bond-forming reaction. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] The First Chemical Synthesis of UDP[6- 3H]-,- D -galactofuranoseEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 14 2005Karina Mariño Abstract Galactofuranose metabolism is a good target for the development of novel chemotherapeutic agents for the treatment of some microbial infections. This is a valid objective because galactofuranose is absent in mammals. Two enzymes are involved in the biosynthesis of molecules containing galactofuranose: a mutase, which catalyzes the interconversion of UDP-Galp and UDP-Galf, and D -galactofuranosyltransferases. The mechanism of action of the mutase and its inhibition is currently being investigated, whereas studies on the galactofuranosyltransferases have been hampered by the lack of a labeled galactofuranose nucleotide. In the present work we describe the chemical synthesis of UDP-,- D -[6- 3H]Galf and we prove its effectiveness for incorporation of radioactive galactofuranose into a natural acceptor. This is the first report on the chemical synthesis of a labeled donor of galactofuranose with the potential for studying the galactofuranosyltransferases independently from the UDP-Galp mutase. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Recombinant expression of an insulin-like peptide 3 (INSL3) precursor and its enzymatic conversion to mature human INSL3FEBS JOURNAL, Issue 18 2009Xiao Luo Insulin-like peptide 3 (INSL3), which is primarily expressed in the Leydig cells of the testes, is a member of the insulin superfamily of peptide hormones. One of its primary functions is to initiate and mediate descent of the testes of the male fetus via interaction with its G protein-coupled receptor, RXFP2. Study of the peptide has relied upon chemical synthesis of the separate A- and B-chains and subsequent chain recombination. To establish an alternative approach to the preparation of human INSL3, we designed and recombinantly expressed a single-chain INSL3 precursor in Escherichia coli cells. The precursor was solubilized from the inclusion body, purified almost to homogeneity by immobilized metal-ion affinity chromatography and refolded efficiently in vitro. The refolded precursor was subsequently converted to mature human INSL3 by sequential endoproteinase Lys-C and carboxypeptidase B treatment. CD spectroscopic analysis and peptide mapping showed that the refolded INSL3 possessed an insulin-like fold with the expected disulfide linkages. Recombinant human INSL3 demonstrated full activity in stimulating cAMP activity in RXFP2-expressing cells. Interestingly, the activity of the single-chain precursor was comparable with that of the mature two-chain INSL3, suggesting that the receptor-binding region within the mid- to C-terminal of B-chain is maintained in an active conformation in the precursor. This study not only provides an efficient approach for mature INSL3 preparation, but also resulted in the acquisition of a useful single-chain template for additional structural and functional studies of the peptide. [source] Immunobiological activities of a chemically synthesized lipid A of Porphyromonas gingivalisFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 4 2000Tomohiko Ogawa Abstract A synthetic lipid A of Porphyromonas gingivalis strain 381 (compound PG-381), which is similar to its natural lipid A, demonstrated no or very low endotoxic activities as compared to Escherichia coli -type synthetic lipid A (compound 506). On the other hand, compound PG-381 had stronger hemagglutinating activities on rabbit erythrocytes than compound 506. Compound PG-381 also induced mitogenic responses in spleen cells from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, as well as LPS-responsive C3H/HeN mice. The addition of polymyxin B resulted in the inhibition of mitogenic activities, however, compound 506 did not show these capacities. Additionally, compound PG-381 showed a lower level of activity in inducing cytokine production in peritoneal macrophages and gingival fibroblasts from C3H/HeN mice, but not C3H/HeJ mice, in comparison to compound 506. Thus, this study demonstrates that the chemical synthesis of lipid A, mimicking the natural lipid A portion of LPS from P. gingivalis, confirms its low endotoxic potency and immunobiological activity. [source] Molecular basis of antibiotic resistance and ,-lactamase inhibition by mechanism-based inactivators: perspectives and future directionsFEMS MICROBIOLOGY REVIEWS, Issue 3 2000Christian Therrien Abstract Antibacterial chemotherapy is particularly striking in the family of penicillins and cephalosporins. Over 40 structurally different ,-lactam molecules are available in 73 formulations and the majority of them are currently prescribed for medical use in hospitals. ,-Lactams are well tolerated by humans with few side effects. They interact very specifically with their bacterial target, the d -alanyl- d -alanine carboxypeptidase-transpeptidase usually referred to as dd -peptidase. The outstanding number of ,-lactamases produced by bacteria represent a serious threat to the clinical utility of ,-lactams. The discovery of ,-lactamase inhibitors was thought to solve, in part, the problem of resistance. Unfortunately, bacteria have evolved new mechanisms of resistance to overcome the inhibitory effects of ,-lactamase inactivators. Here, we summarize the diversified mechanistic features of class A ,-lactamases interactions with mechanism-based inhibitors using available microbiological, kinetic and structural data for the prototype TEM ,-lactamases. A brief historical overview of the strategies developed to counteract ,-lactamases will be presented followed by a short description of the chemical events which lead to the inactivation of TEM ,-lactamase by inhibitors from different classes. Finally, an update on the clinical prevalence of natural and inhibitor-resistant enzyme mutants, the total chemical synthesis to design and synthesize a new structure and produced a broad spectrum ,-lactamase inhibitor that mimics the ,-lactam ring, but does not contain it is discussed. [source] Novel terpenyl esters from Australian finger lime (Citrus australasica) peel extractFLAVOUR AND FRAGRANCE JOURNAL, Issue 3 2009Estelle Delort Abstract The volatile constituents of the peel solvent extract of the Australian finger lime Citrus australasica were analysed by GC,MS. Besides limonene, isomenthone was a major component, which is rare in Citrus species. Six new terpenyl esters were also identified and confirmed by chemical synthesis: citronellyl 2-methylbutanoate; 1,8(10)- p -menthadien-9-yl propanoate; 1,8(10)- p -menthadien-9-yl 2-methylbutanoate; 1,8(10)- p -menthadien-9-yl 3-methylbutanoate; 1- p -menthen-9-yl 2-methylbutanoate; and 1- p -menthen-9-yl 3-methylbutanoate. To the best of our knowledge, the last four compounds have never before been identified in a natural product extract. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||||||||