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Sample records for acyl imines catalyzed

  1. Rhodium-catalyzed asymmetric hydrogenation of unprotected NH imines assisted by a thiourea.

    Zhao, Qingyang; Wen, Jialin; Tan, Renchang; Huang, Kexuan; Metola, Pedro; Wang, Rui; Anslyn, Eric V; Zhang, Xumu

    2014-08-04

    Asymmetric hydrogenation of unprotected NH imines catalyzed by rhodium/bis(phosphine)-thiourea provided chiral amines with up to 97% yield and 95% ee. (1)H NMR studies, coupled with control experiments, implied that catalytic chloride-bound intermediates were involved in the mechanism through a dual hydrogen-bonding interaction. Deuteration experiments proved that the hydrogenation proceeded through a pathway consistent with an imine. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Rh(III)-catalyzed olefination of N-sulfonyl imines: synthesis of ortho-olefinated benzaldehydes.

    Zhang, Tao; Wu, Lamei; Li, Xingwei

    2013-12-20

    Rh(III)-catalyzed olefination of N-sulfonyl imines using acrylates and styrenes has been achieved for the synthesis of ortho-olefinated benaldehydes. This reaction proceeds via a chelation assisted C-H olefination/in situ hydrolysis process.

  3. Highly selective formation of imines catalyzed by silver nanoparticles supported on alumina

    Mielby, Jerrik Jørgen; Poreddy, Raju; Engelbrekt, Christian

    2014-01-01

    The oxidative dehydrogenation of alcohols to aldehydes catalyzed by Ag nanoparticles supported on Al2O3 was studied. The catalyst promoted the direct formation of imines by tandem oxidative dehydrogenation and condensation of alcohols and amines. The reactions were performed under mild conditions......-2 in the gas phase. The use of an efficient and selective Ag catalyst for the oxidative dehydrogenation of alcohol in the presence of amines gives a new green reaction protocol for imine synthesis. (C) 2014, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B...... and afforded the imines in high yield (up to 99%) without any byproducts other than H2O. The highest activity was obtained over 5 wt% Ag/Al2O3 in toluene with air as oxidant. The reactions were also performed under oxidant-free conditions where the reaction was driven to the product side by the production of H...

  4. An Efficient Synthesis of Substituted Quinolines via Indium(III) Chloride Catalyzed Reaction of Imines with Alkynes

    Zhu, Mei; Fu, Weijun; Xun, Chen; Zou, Guanglong

    2012-01-01

    An efficient synthetic method for the preparation of quinolines through indium(III) chloride-catalyzed tandem addition-cyclization-oxidation reactions of imines with alkynes was developed. The processes can provide a diverse range of quinoline derivatives in good yields from simple imines and alkynes

  5. Autoinduced catalysis and inverse equilibrium isotope effect in the frustrated Lewis pair catalyzed hydrogenation of imines.

    Tussing, Sebastian; Greb, Lutz; Tamke, Sergej; Schirmer, Birgitta; Muhle-Goll, Claudia; Luy, Burkhard; Paradies, Jan

    2015-05-26

    The frustrated Lewis pair (FLP)-catalyzed hydrogenation and deuteration of N-benzylidene-tert-butylamine (2) was kinetically investigated by using the three boranes B(C6F5)3 (1), B(2,4,6-F3-C6H2)3 (4), and B(2,6-F2-C6H3)3 (5) and the free activation energies for the H2 activation by FLP were determined. Reactions catalyzed by the weaker Lewis acids 4 and 5 displayed autoinductive catalysis arising from a higher free activation energy (2 kcal mol(-1)) for the H2 activation by the imine compared to the amine. Surprisingly, the imine reduction using D2 proceeded with higher rates. This phenomenon is unprecedented for FLP and resulted from a primary inverse equilibrium isotope effect. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Transition Metal Catalyzed Synthesis of Carboxylic Acids, Imines, and Biaryls

    Santilli, Carola; Madsen, Robert

    the carboxylate.  Manganese catalyzed radical Kumada-type reaction between aryl halidesand aryl Grignard reagents. The reaction between aryl halides and aryl Grignard reagents catalyzed by MnCl2 has been extended to several methyl-substituted aryl iodide reagents byperforming the reaction at 120 ˚C in a microwave...... oven (Scheme ii). A limitation of the heterocoupling process is the concomitant dehalogenation of the aryl halide and homocoupling of the Grignard reagent leading low to moderate yields of the desired heterocoupling product. The mechanism of the cross-coupling process was investigated by performing two...

  7. Dehydrogenative Synthesis of Imines from Alcohols and Amines Catalyzed by a Ruthenium N-Heterocyclic Carbene Complex

    Maggi, Agnese; Madsen, Robert

    2012-01-01

    A new method for the direct synthesis of imines from alcohols and amines is described where hydrogen gas is liberated. The reaction is catalyzed by the ruthenium N-heterocyclic carbene complex [RuCl2(IiPr)(p-cymene)] in the presence of the ligand DABCO and molecular sieves. The imination can...... be applied to a variety of primary alcohols and amines and can be combined with a subsequent addition reaction. A deuterium labeling experiment indicates that the catalytically active species is a ruthenium dihydride. The reaction is believed to proceed by initial dehydrogenation of the alcohol...

  8. Rhodium(III)-catalyzed three-component reaction of imines, alkynes, and aldehydes through C-H activation.

    Huang, Ji-Rong; Song, Qiang; Zhu, Yu-Qin; Qin, Liu; Qian, Zhi-Yong; Dong, Lin

    2014-12-15

    An efficient rhodium(III)-catalyzed tandem three-component reaction of imines, alkynes and aldehydes through CH activation has been developed. High stereo- and regioselectivity, as well as good yields were obtained in most cases. The simple and atom-economical approach offers a broad scope of substrates, providing polycyclic skeletons with potential biological properties. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Asymmetric Chemoenzymatic Reductive Acylation of Ketones by a Combined Iron-Catalyzed Hydrogenation-Racemization and Enzymatic Resolution Cascade

    El-Sepelgy, Osama; Brzozowska, Aleksandra; Rueping, Magnus

    2017-01-01

    . By merging the iron-catalyzed redox reactions with enantioselective enzymatic acylations a wide range of benzylic, aliphatic and (hetero)aromatic ketones, as well as diketones, were reductively acylated. The corresponding products were isolated with high

  10. o-Naphthoquinone-Catalyzed Aerobic Oxidation of Amines to (Ket)imines: A Modular Catalyst Approach.

    Goriya, Yogesh; Kim, Hun Young; Oh, Kyungsoo

    2016-10-07

    A modular aerobic oxidation of amines to imines has been achieved using an ortho-naphthoquinone (o-NQ) catalyst. The cooperative catalyst system of o-NQ and Cu(OAc) 2 enabled the formation of homocoupled imines from benzylamines, while the presence of TFA helped the formation of cross-coupled imines in excellent yields. The current mild aerobic oxidation protocol could also be applied to the oxidation of secondary amines to imines or ketimines with the help of cocatalyst, Ag 2 CO 3 , with excellent yields.

  11. α,β-Unsaturated imines via Ru-catalyzed coupling of allylic alcohols and amines.

    Rigoli, Jared W; Moyer, Sara A; Pearce, Simon D; Schomaker, Jennifer M

    2012-03-07

    A convenient synthesis of α,β-unsaturated imines requiring only an allylic alcohol, an amine and a Ru catalyst has been developed. The use of large excesses of oxidant and the purification of sensitive intermediates can be avoided.

  12. Cholinesterase catalyzed hydrolysis of O-acyl derivatives of serotonin

    Makhaeva, G.F.; Suvorov, N.N.; Ginodman, L.N.; Antonov, V.K.; AN SSSR, Moscow. Inst. Bioorganicheskoj Khimii)

    1977-01-01

    Hydrolysis of O acyl serotonin derivatives containing the residues of monocarbon dicarbon and amino acids under the effect of horse serum butyryl cholinesterase and bull erythrocytic acetylcholinesterase has been studied. It has been established, that acetylcholinesterase hydrolizes O acetylserotonin only; butyrylcholinesterase hydrolizes all the compounds investigated, except for 5,5'-terephthaloildioxytriptamine. The kinetic parameters of hydrolysis were determined. O acyl serotonin derivatives turned out good substrates of butylrylcholinesterase; serotonin and 5.5'-terephtaloildioxytriptamine are effective competitine inhibitors of the enzyme. Estimating of resistance of O acyl serotonin derivatines to blood cholinesterase effect under physiological conditions shows that the compounds investigated with the exception of 5,5'-terephthaloildioxytriptamine must be quickly hydrolyzed under butyrylcholinesterase action. 5,5'-terephthaloildioxytriptamine is suggested as a radioprotective preparation with the prolonged effect, which agrees with the biological test results

  13. Lipase-catalyzed biodiesel synthesis with different acyl acceptors

    Ognjanović Nevena D.

    2008-01-01

    Full Text Available Biodiesel is an alternative fuel for diesel engine that is environmentally acceptable. Conventionally, biodiesel is produced by transesterification of triglycerides and short alcohols in the presence of an acid or an alkaline catalyst. There are several problems associated with this kind of production that can be resolved by using lipase as the biocatalyst. The aim of the present work was to investigate novel acyl acceptors for biodiesel production. 2-Propanol and n-butanol have a less negative effect on lipase stability, and they also improve low temperature properties of the fuel. However, excess alcohol leads to inactivation of the enzyme, and glycerol, a major byproduct, can block the immobilized enzyme, resulting in low enzymatic activity. This problem was solved by using methyl acetate as acyl acceptor. Triacetylglycerol is produced instead of glycerol, and it has no negative effect on the activity of the lipase.

  14. Copper(II)-catalyzed exo and enantioselective cycloadditions of azomethine imines.

    Sibi, Mukund P; Rane, Digamber; Stanley, Levi M; Soeta, Takahiro

    2008-07-17

    A strategy for exo and enantioselective 1,3-dipolar cycloaddition of azomethine imines to 2-acryloyl-3-pyrazolidinone is described. The corresponding cycloadducts are isolated with high diastereoselectivities (up to >96:4 exo/endo) and enantioselectivities (up to 98% ee).

  15. In(OTf)3 catalyzed allylation reaction of imines with tetraallyltin

    Xiao Ning Wei; Ling Yan Liu; Bing Wang; Wei Xing Chang; Jing Li

    2009-01-01

    In the presence of catalytic amount of In(OTf)3 (10 mol%), a series of aldimines reacted with tetraallyltin in a 2:1 molar ratio to afford the corresponding homoallylic amines in good yields. The good atom efficiency was achieved under mild reaction conditions and a new protocol (allyl)4Sn/In(OTf)3 for simple imines was developed.

  16. The isomerization of allylrhodium intermediates in the rhodium-catalyzed nucleophilic allylation of cyclic imines.

    Hepburn, Hamish B; Lam, Hon Wai

    2014-10-20

    Allylrhodium species generated from potassium allyltrifluoroborates can undergo isomerization by 1,4-rhodium(I) migration to give more complex isomers, which then react with cyclic imines to provide products with up to three new stereochemical elements. High enantioselectivities are obtained using chiral diene-rhodium complexes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Ruthenium(III Chloride Catalyzed Acylation of Alcohols, Phenols, and Thiols in Room Temperature Ionic Liquids

    Mingzhong Cai

    2009-09-01

    Full Text Available Ruthenium(III chloride-catalyzed acylation of a variety of alcohols, phenols, and thiols was achieved in high yields under mild conditions (room temperature in the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]. The ionic liquid and ruthenium catalyst can be recycled at least 10 times. Our system not only solves the basic problem of ruthenium catalyst reuse, but also avoids the use of volatile acetonitrile as solvent.

  18. Asymmetric Chemoenzymatic Reductive Acylation of Ketones by a Combined Iron-Catalyzed Hydrogenation-Racemization and Enzymatic Resolution Cascade

    El-Sepelgy, Osama

    2017-02-28

    A general and practical process for the conversion of prochiral ketones into the corresponding chiral acetates has been realized. An iron carbonyl complex is reported to catalyze the hydrogenation-dehydrogenation-hydrogenation of prochiral ketones. By merging the iron-catalyzed redox reactions with enantioselective enzymatic acylations a wide range of benzylic, aliphatic and (hetero)aromatic ketones, as well as diketones, were reductively acylated. The corresponding products were isolated with high yields and enantioselectivities. The use of an iron catalyst together with molecular hydrogen as the hydrogen donor and readily available ethyl acetate as acyl donor make this cascade process highly interesting in terms of both economic value and environmental credentials.

  19. Erbium trifluoromethanesulfonate-catalyzed Friedel–Crafts acylation using aromatic carboxylic acids as acylating agents under monomode-microwave irradiation

    Tran, Phuong Hoang; Hansen, Poul Erik; Nguyen, Hai Truong

    2015-01-01

    Erbium trifluoromethanesulfonate is found to be a good catalyst for the Friedel–Crafts acylation of arenes containing electron-donating substituents using aromatic carboxylic acids as the acylating agents under microwave irradiation. An effective, rapid and waste-free method allows the preparation...... of a wide range of aryl ketones in good yields and in short reaction times with minimum amounts of waste...

  20. Preparation of 5-acyl- and 5-aryl-substituted 1-(benzyloxy)pyrazoles via directed ortho-lithiation/transmetalation and palladium catalyzed cross- coupling

    Kristensen, Jesper Langgaard; Begtrup, M.; Vedsø, P.

    1998-01-01

    Palladium(0) catalyzed cross-coupling of 1-(benzyloxy)pyrazol-5-ylzinc halides 3a,b, prepared by transmetalation of 1-(benzyloxy)-5-lithiopyrazole (2), with acyl chlorides produced 5 acyl-1-(benzyloxy)pyrazoles 4a-d in high yields. Similar coupling of the pyrazol-5-ylzinc halide with amino-, hydr...

  1. Copper(II)/amine synergistically catalyzed enantioselective alkylation of cyclic N-acyl hemiaminals with aldehydes.

    Sun, Shutao; Mao, Ying; Lou, Hongxiang; Liu, Lei

    2015-07-07

    The first catalytic asymmetric alkylation of N-acyl quinoliniums with aldehydes has been described. A copper/amine synergistic catalytic system has been developed, allowing the addition of functionalized aldehydes to a wide range of electronically varied N-acyl quinoliniums in good yields with excellent enantiocontrol. The synergistic catalytic system was also effective for N-acyl dihydroisoquinoliniums and β-caboliniums, demonstrating the general applicability of the protocol in the enantioselective alkylation of diverse cyclic N-acyl hemiaminals.

  2. Pilot batch production of specific-structured lipids by lipase-catalyzed interesterification: preliminary study on incorporation and acyl migration

    Xu, Xuebing; Balchen, Steen; Høy, Carl-Erik

    1998-01-01

    Effects of water content, reaction time and their relationships in the production of two types of specific-structured lipids (sn-MLM- and sn-LML-types: L-long chain fatty acids; M-medium chain fatty acids) by lipase-catalyzed interesterification in a solvent-free system were studied...... of two totally position-opposed lipids can be observed. Presumably these are caused by the different chain length of the fatty acids. The relationships between reaction time and water content are inverse and give a quantitative prediction of incorporation and acyl migration in selected reaction...

  3. Toward Green Acylation of (Heteroarenes: Palladium-Catalyzed Carbonylation of Olefins to Ketones

    Jie Liu

    2017-11-01

    Full Text Available Green Friedel–Crafts acylation reactions belong to the most desired transformations in organic chemistry. The resulting ketones constitute important intermediates, building blocks, and functional molecules in organic synthesis as well as for the chemical industry. Over the past 60 years, advances in this topic have focused on how to make this reaction more economically and environmentally friendly by using green acylating conditions, such as stoichiometric acylations and catalytic homogeneous and heterogeneous acylations. However, currently well-established methodologies for their synthesis either produce significant amounts of waste or proceed under harsh conditions, limiting applications. Here, we present a new protocol for the straightforward and selective introduction of acyl groups into (hetero­arenes without directing groups by using available olefins with inexpensive CO. In the presence of commercial palladium catalysts, inter- and intramolecular carbonylative C–H functionalizations take place with good regio- and chemoselectivity. Compared to classical Friedel–Crafts chemistry, this novel methodology proceeds under mild reaction conditions. The general applicability of this methodology is demonstrated by the direct carbonylation of industrial feedstocks (ethylene and diisobutene as well as of natural products (eugenol and safrole. Furthermore, synthetic applications to drug molecules are showcased.

  4. Uncovering Key Structural Features of an Enantioselective Peptide-Catalyzed Acylation Utilizing Advanced NMR Techniques

    Procházková, Eliška; Kolmer, A.; Ilgen, J.; Schwab, M.; Kaltschnee, L.; Fredersdorf, M.; Schmidts, V.; Wende, R. C.; Schreiner, P. R.; Thiele, C. M.

    2016-01-01

    Roč. 55, č. 51 (2016), s. 15754-15759 ISSN 1433-7851 Institutional support: RVO:61388963 Keywords : conformational analysis * enantioselective acylations * NMR spectroscopy * pure shift NMR * RDCs Subject RIV: CC - Organic Chemistry Impact factor: 11.994, year: 2016

  5. Theoretical study on the nitration of methane by acyl nitrate catalyzed by H-ZSM5 zeolite.

    Silva, Alexander Martins; Nascimento, Marco Antonio Chaer

    2008-09-25

    A theoretical study on the nitration of methane by acyl nitrate catalyzed by HZSM-5 zeolite is reported. The zeolite was represented by a "double ring" 20T cluster. The calculations were performed at the DFT/X3LYP/6-31G** and MP2/6-31G** levels. The first step of the mechanism involves the protonation of the acyl nitrate by the zeolite and the formation of a nitronium-like ion. The reaction proceeds through a concerted step with the attack of the methane molecule by the nitronium-like ion and the simultaneous transfer of a proton from the methane molecule to the zeolite, thus reconstructing the acidic site. The activation energies for the first and second steps of this reaction are, respectively, 14.09 and 10.14 kcal/mol at X3LYP/6-31G** level and 16.68 and 13.85 kcal/mol at the MP2/6-31G**.

  6. Acid catalyzed solvent free synthesis of new 1-acyl-4-benzhydryl substituted pyrazoles

    Sher, M.; Kausar, T.; Riaz, N.; Sharif, A.

    2016-01-01

    A convenient, cost effective and environmentally benign methodology has been developed, which delivered fourteen new 1-acyl-4-benzhyrdyl substituted pyrazole derivatives under solvent free conditions. Target compounds were synthesized in good to excellent yields simply by grinding reactants in a pestle and mortar with catalytic amount of conc. H/sub 2/SO/sub 4/. All the newly formed compounds were fully characterized with the help of detailed spectroscopic techniques including FTIR, NMR and GC-MS. (author)

  7. Oxidative N-Heterocyclic Carbene-Catalyzed γ-Carbon Addition of Enals to Imines: Mechanistic Studies and Access to Antimicrobial Compounds.

    Zheng, Peng-Cheng; Cheng, Jiajia; Su, Shihu; Jin, Zhichao; Wang, Yu-Huang; Yang, Song; Jin, Lin-Hong; Song, Bao-An; Chi, Yonggui Robin

    2015-07-06

    The reaction mechanism of the γ-carbon addition of enal to imine under oxidative N-heterocyclic carbene catalysis is studied experimentally. The oxidation, γ-carbon deprotonation, and nucleophilic addition of γ-carbon to imine were found to be facile steps. The results of our study also provide highly enantioselective access to tricyclic sulfonyl amides that exhibit interesting antimicrobial activities against X. oryzae, a bacterium that causes bacterial disease in rice growing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. A chiral Brønsted acid-catalyzed highly enantioselective Mannich-type reaction of α-diazo esters with in situ generated N-acyl ketimines.

    Unhale, Rajshekhar A; Sadhu, Milon M; Ray, Sumit K; Biswas, Rayhan G; Singh, Vinod K

    2018-04-03

    A chiral phosphoric acid-catalyzed asymmetric Mannich-type reaction of α-diazo esters with in situ generated N-acyl ketimines, derived from 3-hydroxyisoindolinones has been demonstrated in this communication. A variety of isoindolinone-based α-amino diazo esters bearing a quaternary stereogenic center were afforded in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). Furthermore, the synthetic utility of the products has been depicted by the hydrogenation of the diazo moiety of adducts.

  9. A Novel Glucosylation Reaction on Anthocyanins Catalyzed by Acyl-Glucose–Dependent Glucosyltransferase in the Petals of Carnation and Delphinium[C][W

    Matsuba, Yuki; Sasaki, Nobuhiro; Tera, Masayuki; Okamura, Masachika; Abe, Yutaka; Okamoto, Emi; Nakamura, Haruka; Funabashi, Hisakage; Takatsu, Makoto; Saito, Mikako; Matsuoka, Hideaki; Nagasawa, Kazuo; Ozeki, Yoshihiro

    2010-01-01

    Glucosylation of anthocyanin in carnations (Dianthus caryophyllus) and delphiniums (Delphinium grandiflorum) involves novel sugar donors, aromatic acyl-glucoses, in a reaction catalyzed by the enzymes acyl-glucose–dependent anthocyanin 5(7)-O-glucosyltransferase (AA5GT and AA7GT). The AA5GT enzyme was purified from carnation petals, and cDNAs encoding carnation Dc AA5GT and the delphinium homolog Dg AA7GT were isolated. Recombinant Dc AA5GT and Dg AA7GT proteins showed AA5GT and AA7GT activities in vitro. Although expression of Dc AA5GT in developing carnation petals was highest at early stages, AA5GT activity and anthocyanin accumulation continued to increase during later stages. Neither Dc AA5GT expression nor AA5GT activity was observed in the petals of mutant carnations; these petals accumulated anthocyanin lacking the glucosyl moiety at the 5 position. Transient expression of Dc AA5GT in petal cells of mutant carnations is expected to result in the transfer of a glucose moiety to the 5 position of anthocyanin. The amino acid sequences of Dc AA5GT and Dg AA7GT showed high similarity to glycoside hydrolase family 1 proteins, which typically act as β-glycosidases. A phylogenetic analysis of the amino acid sequences suggested that other plant species are likely to have similar acyl-glucose–dependent glucosyltransferases. PMID:20971893

  10. Cp*Co(III) Catalyzed Site-Selective C-H Activation of Unsymmetrical O-Acyl Oximes: Synthesis of Multisubstituted Isoquinolines from Terminal and Internal Alkynes.

    Sun, Bo; Yoshino, Tatsuhiko; Kanai, Motomu; Matsunaga, Shigeki

    2015-10-26

    The synthesis of isoquinolines by site-selective C-H activation of O-acyl oximes with a Cp*Co(III) catalyst is described. In the presence of this catalyst, the C-H activation of various unsymmetrically substituted O-acyl oximes selectively occurred at the sterically less hindered site, and reactions with terminal as well as internal alkynes afforded the corresponding products in up to 98 % yield. Whereas the reactions catalyzed by the Cp*Co(III) system proceeded with high site selectivity (15:1 to 20:1), use of the corresponding Cp*Rh(III) catalysts led to low selectivities and/or yields when unsymmetrical O-acyl oximes and terminal alkynes were used. Deuterium labeling studies indicate a clear difference in the site selectivity of the C-H activation step under Cp*Co(III) and Cp*Rh(III) catalysis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. A General and Selective Rhodium-Catalyzed Reduction of Amides, N-Acyl Amino Esters, and Dipeptides Using Phenylsilane.

    Das, Shoubhik; Li, Yuehui; Lu, Liang-Qiu; Junge, Kathrin; Beller, Matthias

    2016-05-17

    This article describes a selective reduction of functionalized amides, including N-acyl amino esters and dipeptides, to the corresponding amines using simple [Rh(acac)(cod)]. The catalyst shows excellent chemoselectivity in the presence of different sensitive functional moieties. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Quantitation of acyl migration during lipase-catalyzed acidolysis, and of the regioisomers of structured triacylglycerols formed

    Mu, Huiling; Kurvinen, J.P.; Kallio, H.

    2001-01-01

    degradation, and ranged from 39.0 to 48.7% and 0.6 to 9.3%, respectively. Quantitation of triacylglycerol molecular species was performed by ammonia negative ion chemical ionization (NICI) mass spectrometry (MS). The proportion of ACN (acyl carbon number) 34 species that contained one C-18 fatty acid and two...... C-8:0, in samples analyzed, varied from 12.5 to 23.2%. The selected regioisomers MLM and MML within the ACN 34 species group were quantified by NICI tandem MS (MS/MS) and were in the range of 97.1 to 98.4% and 1.6 to 2.9%, respectively. There was no correlation between the level of acyl migration...

  13. Highly efficient and regioselective acylation of pharmacologically interesting cordycepin catalyzed by lipase in the eco-friendly solvent 2-methyltetrahydrofuran.

    Chen, Zhi-Gang; Zhang, Dan-Ni; Cao, Lin; Han, Yong-Bin

    2013-04-01

    A total of nine lipases and three proteases were tested for enzymatic regioselective acylation(s) of cordycepin with vinyl acetate in organic media. The highest conversion with better initial reaction rate was achieved with immobilized Candida antarctica lipase B (Novozym 435). An eco-friendly solvent 2-methyltetrahydrofuran (MeTHF) was thought to be the most suitable reaction medium. Novozym 435 was found to be a useful biocatalyst for the 25-g scale syntheses of cordycepin acetate (96.2% isolated yield), and the biocatalyst displayed excellent regioselectivity and high operational stability during the transformation. The 5'-substituted cordycepin derivative was the sole detectable product from each acylation reaction. Novozym 435 could be recycled for the synthesis of cordycepin derivative on a 25-g scale and 63% of its original activity was maintained after being reused for 7 batches. MeTHF could be considered as an eco-friendly solvent for the large scale use in biotransformation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Well-defined silica-supported zirconium–imido complexes mediated heterogeneous imine metathesis

    Hamzaoui, Bilel

    2016-02-15

    Upon prolonged thermal exposure under vacuum, a well-defined single-site surface species [(≡Si-O-)Zr(NEt2)3] (1) evolves into an ethylimido complex [(≡Si-O-)Zr(=NEt)NEt2] (2). Reactions of 2 with an imine substrate result in imido/imine (=NRi, R: Et, Ph) exchange (metathesis) with the formation of [(≡Si-O-)Zr(=NPh)NEt2] (3). Compounds 2 and 3 effectively catalyze imine/imine cross-metathesis and are thus considered as the first heterogeneous catalysts active for imine metathesis. © The Royal Society of Chemistry 2016.

  15. Well-defined silica-supported zirconium–imido complexes mediated heterogeneous imine metathesis

    Hamzaoui, Bilel; Pelletier, Jeremie; Abou-Hamad, Edy; Basset, Jean-Marie

    2016-01-01

    Upon prolonged thermal exposure under vacuum, a well-defined single-site surface species [(≡Si-O-)Zr(NEt2)3] (1) evolves into an ethylimido complex [(≡Si-O-)Zr(=NEt)NEt2] (2). Reactions of 2 with an imine substrate result in imido/imine (=NRi, R: Et, Ph) exchange (metathesis) with the formation of [(≡Si-O-)Zr(=NPh)NEt2] (3). Compounds 2 and 3 effectively catalyze imine/imine cross-metathesis and are thus considered as the first heterogeneous catalysts active for imine metathesis. © The Royal Society of Chemistry 2016.

  16. Two bifunctional enzymes from the marine protist Thraustochytrium roseum: biochemical characterization of wax ester synthase/acyl-CoA:diacylglycerol acyltransferase activity catalyzing wax ester and triacylglycerol synthesis.

    Zhang, Nannan; Mao, Zejing; Luo, Ling; Wan, Xia; Huang, Fenghong; Gong, Yangmin

    2017-01-01

    Triacylglycerols (TAGs) and wax esters (WEs) are important neutral lipids which serve as energy reservoir in some plants and microorganisms. In recent years, these biologically produced neutral lipids have been regarded as potential alternative energy sources for biofuel production because of the increased interest on developing renewable and environmentally benign alternatives for fossil fuels. In bacteria, the final step in TAG and WE biosynthetic pathway is catalyzed by wax ester synthase/acyl coenzyme A (acyl-CoA):diacylglycerol acyltransferase (WS/DGAT). This bifunctional WS/DGAT enzyme is also a key enzyme in biotechnological production of liquid WE via engineering of plants and microorganisms. To date, knowledge about this class of biologically and biotechnologically important enzymes is mainly from biochemical characterization of WS/DGATs from Arabidopsis, jojoba and some bacteria that can synthesize both TAGs and WEs intracellularly, whereas little is known about WS/DGATs from eukaryotic microorganisms. Here, we report the identification and characterization of two bifunctional WS/DGAT enzymes (designated TrWSD4 and TrWSD5) from the marine protist Thraustochytrium roseum . Both TrWSD4 and TrWSD5 comprise a WS-like acyl-CoA acyltransferase domain and the recombinant proteins purified from Escherichia coli Rosetta (DE3) have substantial WS and lower DGAT activity. They exhibit WS activity towards various-chain-length saturated and polyunsaturated acyl-CoAs and fatty alcohols ranging from C 10 to C 18 . TrWSD4 displays WS activity with the lowest K m value of 0.14 μM and the highest k cat / K m value of 1.46 × 10 5  M -1  s -1 for lauroyl-CoA (C 12:0 ) in the presence of 100 μM hexadecanol, while TrWSD5 exhibits WS activity with the lowest K m value of 0.96 μM and the highest k cat / K m value of 9.83 × 10 4  M -1  s -1 for decanoyl-CoA (C 10:0 ) under the same reaction condition. Both WS/DGAT enzymes have the highest WS activity at 37 and 47

  17. Stereoselective Reduction of Imines with Trichlorosilane Using Solid-Supported Chiral Picolinamides

    Sílvia D. Fernandes

    2016-09-01

    Full Text Available The stereoselective reduction of imines with trichlorosilane catalyzed by chiral Lewis bases is a well-established procedure for the synthesis of enantio-enriched amines. Five supported cinchona-based picolinamides have been prepared and their activity tested in a model reaction. The comparison of different supporting materials revealed that polystyrene gave better results than silica in terms of stereoselectivity. The applicability of the solid-supported catalyst of choice to the reduction of different imines was also demonstrated. Additionally, for the first time, a catalytic reactor containing a polymer-immobilized chiral picolinamide has been employed for the stereoselective reduction of imines with trichlorosilane under continuous flow conditions.

  18. Nickel-Catalyzed C–CN Bond Formation via Decarbonylative Cyanation of Esters, Amides, and Intramolecular Recombination Fragment Coupling of Acyl Cyanides

    Chatupheeraphat, Adisak; Liao, Hsuan-Hung; Lee, Shao-Chi; Rueping, Magnus

    2017-01-01

    An efficient nickel-catalyzed decarbonylative cyanation reaction which allows the direct functional-group interconversion of readily available esters into the corresponding nitriles was developed. This reaction successfully offers access to structurally diverse nitriles with high efficiency and excellent functional-group tolerance and provides a good alternative to classical synthetic pathways from diazonium salts or organic halide compounds.

  19. Nickel-Catalyzed C–CN Bond Formation via Decarbonylative Cyanation of Esters, Amides, and Intramolecular Recombination Fragment Coupling of Acyl Cyanides

    Chatupheeraphat, Adisak

    2017-08-07

    An efficient nickel-catalyzed decarbonylative cyanation reaction which allows the direct functional-group interconversion of readily available esters into the corresponding nitriles was developed. This reaction successfully offers access to structurally diverse nitriles with high efficiency and excellent functional-group tolerance and provides a good alternative to classical synthetic pathways from diazonium salts or organic halide compounds.

  20. Formation of enamines by alkylation of imines

    Heiszwolf, G.J.; Kloosterziel, H.

    1966-01-01

    cf. CA 64, 12473c. With ice-cooling, 1 equiv. alkylating agent was added to one equiv. of the imine in 1M soln. in a solvent in the presence of NaH to give both N- and C-alkylated products. The following summarizes the date (imine, solvent, alkylating agent, % unreacted imine, % N-alkylated product,

  1. Ligand-Controlled Chemoselective C(acyl)–O Bond vs C(aryl)–C Bond Activation of Aromatic Esters in Nickel Catalyzed C(sp2)–C(sp3) Cross-Couplings

    Chatupheeraphat, Adisak

    2018-02-20

    A ligand-controlled and site-selective nickel catalyzed Suzuki-Miyaura cross-coupling reaction with aromatic esters and alkyl organoboron reagents as coupling partners was developed. This methodology provides a facile route for C(sp2)-C(sp3) bond formation in a straightforward fashion by successful suppression of the undesired β-hydride elimination process. By simply switching the phosphorus ligand, the ester substrates are converted into the alkylated arenes and ketone products, respectively. The utility of this newly developed protocol was demonstrated by its wide substrate scope, broad functional group tolerance and application in the synthesis of key intermediates for the synthesis of bioactive compounds. DFT studies on the oxidative addition step helped rationalizing this intriguing reaction chemoselectivity: whereas nickel complexes with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative addition step leading to the alkylated product via a decarbonylative process, nickel complexes with monodentate phosphorus ligands favor activation of the C(acyl)-O bond, which later generates the ketone product.

  2. Preparation of poly (imine imine ketone) s microshells

    Cui Yi; Luo Xuan; Fan Yongheng; Zhang Lin; Liu Lei; Lin Runxiong

    2010-01-01

    Large diameter (0.6 ∼ 2.0 mm) microshells of poly (imine imine ketone) s (PIIKs) were prepared by micro-liquid technique and double-layer latex technique. A double T-channel droplet generator was designed and developed for the fabrication of PIIKs microshells of controlled size continuously. Manipulative conditions of the diameter and thickness of shells were studied, and the effect of density mismatch on shell quality was discussed. Phase separation during the preparation process affects the morphology of shells. Spinodal phase separation tends to occur at the outer surface of the shells, while binodal phase separation at the inner surface. The diameters of PIIKs shells were measured, 88% of which vary in ± 5% of the average diameter. The sphericity is better than 99%. (authors)

  3. Thermophilic Coenzyme B12-Dependent Acyl Coenzyme A (CoA) Mutase from Kyrpidia tusciae DSM 2912 Preferentially Catalyzes Isomerization of (R)-3-Hydroxybutyryl-CoA and 2-Hydroxyisobutyryl-CoA.

    Weichler, Maria-Teresa; Kurteva-Yaneva, Nadya; Przybylski, Denise; Schuster, Judith; Müller, Roland H; Harms, Hauke; Rohwerder, Thore

    2015-07-01

    The recent discovery of a coenzyme B12-dependent acyl-coenzyme A (acyl-CoA) mutase isomerizing 3-hydroxybutyryl- and 2-hydroxyisobutyryl-CoA in the mesophilic bacterium Aquincola tertiaricarbonis L108 (N. Yaneva, J. Schuster, F. Schäfer, V. Lede, D. Przybylski, T. Paproth, H. Harms, R. H. Müller, and T. Rohwerder, J Biol Chem 287:15502-15511, 2012, http://dx.doi.org/10.1074/jbc.M111.314690) could pave the way for a complete biosynthesis route to the building block chemical 2-hydroxyisobutyric acid from renewable carbon. However, the enzyme catalyzes only the conversion of the stereoisomer (S)-3-hydroxybutyryl-CoA at reasonable rates, which seriously hampers an efficient combination of mutase and well-established bacterial poly-(R)-3-hydroxybutyrate (PHB) overflow metabolism. Here, we characterize a new 2-hydroxyisobutyryl-CoA mutase found in the thermophilic knallgas bacterium Kyrpidia tusciae DSM 2912. Reconstituted mutase subunits revealed highest activity at 55°C. Surprisingly, already at 30°C, isomerization of (R)-3-hydroxybutyryl-CoA was about 7,000 times more efficient than with the mutase from strain L108. The most striking structural difference between the two mutases, likely determining stereospecificity, is a replacement of active-site residue Asp found in strain L108 at position 117 with Val in the enzyme from strain DSM 2912, resulting in a reversed polarity at this binding site. Overall sequence comparison indicates that both enzymes descended from different prokaryotic thermophilic methylmalonyl-CoA mutases. Concomitant expression of PHB enzymes delivering (R)-3-hydroxybutyryl-CoA (beta-ketothiolase PhaA and acetoacetyl-CoA reductase PhaB from Cupriavidus necator) with the new mutase in Escherichia coli JM109 and BL21 strains incubated on gluconic acid at 37°C led to the production of 2-hydroxyisobutyric acid at maximal titers of 0.7 mM. Measures to improve production in E. coli, such as coexpression of the chaperone MeaH and repression of

  4. Catalytic asymmetric diels-alder reaction of quinone imine ketals: a site-divergent approach.

    Hashimoto, Takuya; Nakatsu, Hiroki; Maruoka, Keiji

    2015-04-07

    The catalytic asymmetric Diels-Alder reaction of quinone imine ketals with diene carbamates catalyzed by axially chiral dicarboxylic acids is reported herein. A variety of primary and secondary alkyl-substituted quinone derivatives which have not been applied in previous asymmetric quinone Diels-Alder reactions could be employed using this method. More importantly, we succeeded in developing a strategy to divert the reaction site in unsymmetrical 3-alkyl quinone imine ketals from the inherently favored unsubstituted C=C bond to the disfavored alkyl-substituted C=C bond. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Quantum chemical study of penicillin: Reactions after acylation

    Li, Rui; Feng, Dacheng; Zhu, Feng

    The density functional theory methods were used on the model molecules of penicillin to determine the possible reactions after their acylation on ?-lactamase, and the results were compared with sulbactam we have studied. The results show that, the acylated-enzyme tetrahedral intermediate can evolves with opening of ?-lactam ring as well as the thiazole ring; the thiazole ring-open products may be formed via ?-lactam ring-open product or from tetrahedral intermediate directly. Those products, in imine or enamine form, can tautomerize via hydrogen migration. In virtue of the water-assisted, their energy barriers are obviously reduced.

  6. Imine-based [2]catenanes in water.

    Caprice, Kenji; Pupier, Marion; Kruve, Anneli; Schalley, Christoph A; Cougnon, Fabien B L

    2018-02-07

    We report the efficient condensation of imine-based macrocycles from dialdehyde A and aliphatic diamines B n in pure water. Within the libraries, we identified a family of homologous amphiphilic [2]catenanes, whose self-assembly is primarily driven by the hydrophobic effect. The length and odd-even character of the diamine alkyl linker dictate both the yield and the conformation of the [2]catenanes, whose particular thermodynamic stability further shifts the overall equilibrium in favour of imine condensation. These findings highlight the role played by solvophobic effects in the self-assembly of complex architectures.

  7. The alkylation of imine anions formation of enamines

    Heiszwolf, G.J.; Kloosterziel, H.

    1970-01-01

    The ambident anions derived from imines were alkylated using a variety of solvents and alkylating agents. Under reactive conditions enamines (N-alkylation) are formed as the main products instead of the usually obsd. homologous imines (C-alkylation). The influence of the type of imine, solvent, and

  8. Acylation of Therapeutic Peptides

    Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard

    ) , which promotes intestinal growth and is used to treat bowel disorders such as inflammatory bowel diseases and short bowel syndrome, and the 32 amino acid salmon calcitonin (sCT), which lowers blood calcium and is employed in the treatment of post-menopausal osteoporosis and hypercalcemia. The two...... peptides are similar in size and structure, but oppositely charged at physiological pH. Both peptides were acylated with linear acyl chains of systematically increasing length, where sCT was furthermore acylated at two different positions on the peptide backbone. For GLP-2, we found that increasing acyl...... remained optimal overall. The results indicate that rational acylation of GLP-2 can increase its in vitro intestinal absorption, alone or in combination with permeation enhancers, and are consistent with the initial project hypothesis. For sCT, an unpredicted effect of acylation largely superseded...

  9. THE LATEST ADVANCEMENTS IN THE ACYLATION REACTIONS VIA CROSS-DEHYDROGENATIVE COUPLING AND/OR METAL CATALYSTS

    Soykan Ağar

    2017-12-01

    Full Text Available There are quite many examples in the scientific literature regarding the acylation reactions, especially the metal-catalyzed acylation reactions, metal-free acylation reactions, metal-catalyzed acylation via cross-dehydrogenative coupling (CDC reactions and metal-free acylation via cross-dehydrogenative coupling (CDC reactions. In this review paper, the most important examples of these domains were brought together and their mechanisms were exhibited in a clear, chronological format. Following these, the best example study towards green chemistry with a metal-free and high-yielding route was mentioned and discussed to demonstrate what has achieved in this field regarding the new acylation reaction mechanisms using the advantages of cross-dehydrogenative coupling (CDC reactions. The most prominent studies regarding these domains have been examined thoroughly and the latest progress in this field was explained in detail.

  10. A soluble fatty acyl-acyl carrier protein synthetase from the bioluminescent bacterium Vibrio harveyi.

    Byers, D M; Holmes, C G

    1990-01-01

    An enzyme catalyzing the ligation of long chain fatty acids to bacterial acyl carrier protein (ACP) has been detected and partially characterized in cell extracts of the bioluminescent bacterium Vibrio harveyi. Acyl-ACP synthetase activity (optimal pH 7.5-8.0) required millimolar concentrations of ATP and Mg2+ and was slightly activated by Ca2+, but was inhibited at high ionic strength and by Triton X-100. ACP from either Escherichia coli (apparent Km = 20 microM) or V. harveyi was used as a substrate. Of the [14C]fatty acids tested as substrates (8-18 carbons), a preference for fatty acids less than or equal to 14 carbons in length was observed. Vibrio harveyi acyl-ACP synthetase appears to be a soluble hydrophilic enzyme on the basis of subcellular fractionation and Triton X-114 phase partition assay. The enzyme was not coinduced with luciferase activity or light emission in vivo during the late exponential growth phase in liquid culture. Acyl-ACP synthetase activity was also detected in extracts from the luminescent bacterium Vibrio fischeri, but not Photobacterium phosphoreum. The cytosolic nature and enzymatic properties of V. harveyi acyl-ACP synthetase indicate that it may have a different physiological role than the membrane-bound activity of E. coli, which has been implicated in phosphatidylethanolamine turnover. Acyl-ACP synthetase activity in V. harveyi could be involved in the intracellular activation and elongation of exogenous fatty acids that occurs in this species or in the reactivation of free myristic acid generated by luciferase.

  11. Production of specific-structured lipids by enzymatic interesterification: elucidation of acyl migration by response surface design

    Xu, Xuebing; Skands, Anja; Høy, Carl-Erik

    1998-01-01

    Production of specific-structured lipids (SSL) by lipase-catalyzed interesterification has been attracting more and more attention recently. However, it was found that acyl migration occurs during the reaction and causes the production of by-products. In this paper, the elucidation of acyl...

  12. Chemoselective organocatalytic aerobic oxidation of primary amines to secondary imines.

    Wendlandt, Alison E; Stahl, Shannon S

    2012-06-01

    Biomimetic aerobic oxidation of primary benzylic amines has been achieved by using a quinone catalyst. Excellent selectivity is observed for primary, unbranched benzylic amines relative to secondary/tertiary amines, branched benzylic amines, and aliphatic amines. The exquisite selectivity for benzylic amines enables oxidative self-sorting within dynamic mixtures of amines and imines to afford high yields of cross-coupled imine products.

  13. Characterization of a structurally and functionally diverged acyl-acyl carrier protein desaturase from milkweed seed.

    Cahoon, E B; Coughlan, S J; Shanklin, J

    1997-04-01

    A cDNA for a structurally variant acyl-acyl carrier protein (ACP) desaturase was isolated from milkweed (Asclepias syriaca) seed, a tissue enriched in palmitoleic (16:1delta9)* and cis-vaccenic (18:1delta11) acids. Extracts of Escherichia coli that express the milkweed cDNA catalyzed delta9 desaturation of acyl-ACP substrates, and the recombinant enzyme exhibited seven- to ten-fold greater specificity for palmitoyl (16:0)-ACP and 30-fold greater specificity for myristoyl (14:0)-ACP than did known delta9-stearoyl (18:0)-ACP desaturases. Like other variant acyl-ACP desaturases reported to date, the milkweed enzyme contains fewer amino acids near its N-terminus compared to previously characterized delta9-18:0-ACP desaturases. Based on the activity of an N-terminal deletion mutant of a delta9-18:0-ACP desaturase, this structural feature likely does not account for differences in substrate specificities.

  14. Acyl-Lipid Metabolism

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2013-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:23505340

  15. Plant Acyl-CoA:Lysophosphatidylcholine Acyltransferases (LPCATs) Have Different Specificities in Their Forward and Reverse Reactions*

    Lager, Ida; Yilmaz, Jenny Lindberg; Zhou, Xue-Rong; Jasieniecka, Katarzyna; Kazachkov, Michael; Wang, Peng; Zou, Jitao; Weselake, Randall; Smith, Mark A.; Bayon, Shen; Dyer, John M.; Shockey, Jay M.; Heinz, Ernst; Green, Allan; Banas, Antoni; Stymne, Sten

    2013-01-01

    Acyl-CoA:lysophosphatidylcholine acyltransferase (LPCAT) enzymes have central roles in acyl editing of phosphatidylcholine (PC). Plant LPCAT genes were expressed in yeast and characterized biochemically in microsomal preparations of the cells. Specificities for different acyl-CoAs were similar for seven LPCATs from five different species, including species accumulating hydroxylated acyl groups in their seed oil, with a preference for C18-unsaturated acyl-CoA and low activity with palmitoyl-CoA and ricinoleoyl (12-hydroxyoctadec-9-enoyl)-CoA. We showed that Arabidopsis LPCAT1 and LPCAT2 enzymes catalyzed the acylation and de-acylation of both sn positions of PC, with a preference for the sn-2 position. When acyl specificities of the Arabidopsis LPCATs were measured in the reverse reaction, sn-2-bound oleoyl, linoleoyl, and linolenoyl groups from PC were transferred to acyl-CoA to a similar extent. However, a ricinoleoyl group at the sn-2-position of PC was removed 4–6-fold faster than an oleoyl group in the reverse reaction, despite poor utilization in the forward reaction. The data presented, taken together with earlier published reports on in vivo lipid metabolism, support the hypothesis that plant LPCAT enzymes play an important role in regulating the acyl-CoA composition in plant cells by transferring polyunsaturated and hydroxy fatty acids produced on PC directly to the acyl-CoA pool for further metabolism or catabolism. PMID:24189065

  16. Enhanced reactivities toward amines by introducing an imine arm to the pincer ligand: Direct coupling of two amines to form an imine without oxidant

    He, Lipeng

    2012-07-23

    Dehydrogenative homocoupling of primary alcohols to form esters and coupling of amines to form imines was accomplished using a class of novel pincer ruthenium complexes. The reactivities of the ruthenium pincer complexes for the direct coupling of amines to form imines were enhanced by introducing an imine arm to the pincer ligand. Selective oxidation of benzylamines to imines was achieved using aniline derivatives as the substrate and solvent. © 2012 American Chemical Society.

  17. Enhanced reactivities toward amines by introducing an imine arm to the pincer ligand: Direct coupling of two amines to form an imine without oxidant

    He, Lipeng; Chen, Tao; Gong, Dirong; Lai, Zhiping; Huang, Kuo-Wei

    2012-01-01

    Dehydrogenative homocoupling of primary alcohols to form esters and coupling of amines to form imines was accomplished using a class of novel pincer ruthenium complexes. The reactivities of the ruthenium pincer complexes for the direct coupling of amines to form imines were enhanced by introducing an imine arm to the pincer ligand. Selective oxidation of benzylamines to imines was achieved using aniline derivatives as the substrate and solvent. © 2012 American Chemical Society.

  18. Nickel-Catalyzed Synthesis of Primary Aryl and Heteroaryl Amines via C–O Bond Cleavage

    Yue, Huifeng

    2017-03-13

    A nickel-catalyzed protocol for the conversion of aryl and heteroaryl alcohol derivatives to primary and secondary aromatic amines via C(sp2)-O bond cleavage is described. The new amination protocol can be applied to a range of substrates bearing diverse functional groups and uses readily available benzophenone imines as an effective nitrogen source.

  19. Nickel-Catalyzed Synthesis of Primary Aryl and Heteroaryl Amines via C–O Bond Cleavage

    Yue, Huifeng; Guo, Lin; Liu, Xiangqian; Rueping, Magnus

    2017-01-01

    A nickel-catalyzed protocol for the conversion of aryl and heteroaryl alcohol derivatives to primary and secondary aromatic amines via C(sp2)-O bond cleavage is described. The new amination protocol can be applied to a range of substrates bearing diverse functional groups and uses readily available benzophenone imines as an effective nitrogen source.

  20. Ceria-Based Mixed Oxide Supported Nano-Gold as an Efficient and Durable Heterogeneous Catalyst for Oxidative Dehydrogenation of Amines to Imines Using Molecular Oxygen

    Bashir Ahmad Dar

    2012-06-01

    Full Text Available The present work is intended to determine the catalytic activity of Mixed Oxide supported gold for aerobic oxidative dehydrogenation of amines to imines using Ceria as a main constituent of the each support. The model catalysts Au/CeO2:TiO2 Au/CeO2:SiO2, Au/CeO2:ZrO2 and Au/CeO2:Al2Os were prepared by deposition co-precipitation method and deposition of gold was determined by EDEX analysis. The supported nano-gold catalyzes the dehydrogenation of secondary amines to imines without loss of activity. On recycling good amount of product yield is obtained. Oxidation of secondary amines to imines is carried at 100˚C and almost 90 % conversion was obtained with >99% selectivity. © 2012 BCREC UNDIP. All rights reservedReceived: 26th December 2011; Revised: 7th June 2012; Accepted: 13rd June 2012[How to Cite: B.A. Dar, M. Sharma, B. Singh. (2012. Ceria-Based Mixed Oxide Supported Nano-Gold as an Efficient and Durable Heterogeneous Catalyst for Oxidative Dehydrogenation of Amines to Imines Using Molecular Oxygen. Bulletin of Chemical Reaction Engineering & Catalysis, 7(1: 79-84.  doi:10.9767/bcrec.7.1.1257.79-84][How to Link / DOI: http://dx.doi.org/10.9767/bcrec.7.1.1257.79-84 ] | View in 

  1. Fatty acyl-CoA reductases of birds

    Hellenbrand Janine

    2011-12-01

    Full Text Available Abstract Background Birds clean and lubricate their feathers with waxes that are produced in the uropygial gland, a holocrine gland located on their back above the tail. The type and the composition of the secreted wax esters are dependent on the bird species, for instance the wax ester secretion of goose contains branched-chain fatty acids and unbranched fatty alcohols, whereas that of barn owl contains fatty acids and alcohols both of which are branched. Alcohol-forming fatty acyl-CoA reductases (FAR catalyze the reduction of activated acyl groups to fatty alcohols that can be esterified with acyl-CoA thioesters forming wax esters. Results cDNA sequences encoding fatty acyl-CoA reductases were cloned from the uropygial glands of barn owl (Tyto alba, domestic chicken (Gallus gallus domesticus and domestic goose (Anser anser domesticus. Heterologous expression in Saccharomyces cerevisiae showed that they encode membrane associated enzymes which catalyze a NADPH dependent reduction of acyl-CoA thioesters to fatty alcohols. By feeding studies of transgenic yeast cultures and in vitro enzyme assays with membrane fractions of transgenic yeast cells two groups of isozymes with different properties were identified, termed FAR1 and FAR2. The FAR1 group mainly synthesized 1-hexadecanol and accepted substrates in the range between 14 and 18 carbon atoms, whereas the FAR2 group preferred stearoyl-CoA and accepted substrates between 16 and 20 carbon atoms. Expression studies with tissues of domestic chicken indicated that FAR transcripts were not restricted to the uropygial gland. Conclusion The data of our study suggest that the identified and characterized avian FAR isozymes, FAR1 and FAR2, can be involved in wax ester biosynthesis and in other pathways like ether lipid synthesis.

  2. Fatty acyl-CoA reductases of birds

    2011-01-01

    Background Birds clean and lubricate their feathers with waxes that are produced in the uropygial gland, a holocrine gland located on their back above the tail. The type and the composition of the secreted wax esters are dependent on the bird species, for instance the wax ester secretion of goose contains branched-chain fatty acids and unbranched fatty alcohols, whereas that of barn owl contains fatty acids and alcohols both of which are branched. Alcohol-forming fatty acyl-CoA reductases (FAR) catalyze the reduction of activated acyl groups to fatty alcohols that can be esterified with acyl-CoA thioesters forming wax esters. Results cDNA sequences encoding fatty acyl-CoA reductases were cloned from the uropygial glands of barn owl (Tyto alba), domestic chicken (Gallus gallus domesticus) and domestic goose (Anser anser domesticus). Heterologous expression in Saccharomyces cerevisiae showed that they encode membrane associated enzymes which catalyze a NADPH dependent reduction of acyl-CoA thioesters to fatty alcohols. By feeding studies of transgenic yeast cultures and in vitro enzyme assays with membrane fractions of transgenic yeast cells two groups of isozymes with different properties were identified, termed FAR1 and FAR2. The FAR1 group mainly synthesized 1-hexadecanol and accepted substrates in the range between 14 and 18 carbon atoms, whereas the FAR2 group preferred stearoyl-CoA and accepted substrates between 16 and 20 carbon atoms. Expression studies with tissues of domestic chicken indicated that FAR transcripts were not restricted to the uropygial gland. Conclusion The data of our study suggest that the identified and characterized avian FAR isozymes, FAR1 and FAR2, can be involved in wax ester biosynthesis and in other pathways like ether lipid synthesis. PMID:22151413

  3. Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear factor-4{alpha}.

    Hertz, Rachel; Kalderon, Bella; Byk, Tamara; Berman, Ina; Za'tara, Ghadeer; Mayer, Raphael; Bar-Tana, Jacob

    2005-07-01

    Hepatocyte nuclear factor-4alpha (HNF-4alpha) activity is modulated by natural and xenobiotic fatty acid and fatty acyl-CoA ligands as a function of their chain length, unsaturation, and substitutions. The acyl-CoA site of HNF-4alpha is reported here to consist of the E-F domain, to bind long-chain acyl-CoAs but not the respective free acids, and to catalyze the hydrolysis of bound fatty acyl-CoAs. The free acid pocket, previously reported in the x-ray structure of HNF-4alpha E-domain, entraps fatty acids but excludes acyl-CoAs. The acyl-CoA and free acid sites are distinctive and noncongruent. Free fatty acid products of HNF-4alpha thioesterase may exchange with free acids entrapped in the fatty acid pocket of HNF-4alpha. Cross-talk between the acyl-CoA and free fatty acid binding sites is abrogated by high affinity, nonhydrolyzable acyl-CoA ligands of HNF-4alpha that inhibit its thioesterase activity. Hence, HNF-4alpha transcriptional activity is controlled by its two interrelated acyl ligands and two binding sites interphased in tandem by the thioesterase activity. The acyl-CoA/free-acid and receptor/enzyme duality of HNF-4alpha extends the paradigm of nuclear receptors.

  4. Hydride, hydrogen, proton, and electron affinities of imines and their reaction intermediates in acetonitrile and construction of thermodynamic characteristic graphs (TCGs) of imines as a "molecule ID card".

    Zhu, Xiao-Qing; Liu, Qiao-Yun; Chen, Qiang; Mei, Lian-Rui

    2010-02-05

    A series of 61 imines with various typical structures were synthesized, and the thermodynamic affinities (defined as enthalpy changes or redox potentials in this work) of the imines to abstract hydride anions, hydrogen atoms, and electrons, the thermodynamic affinities of the radical anions of the imines to abstract hydrogen atoms and protons, and the thermodynamic affinities of the hydrogen adducts of the imines to abstract electrons in acetonitrile were determined by using titration calorimetry and electrochemical methods. The pure heterolytic and homolytic dissociation energies of the C=N pi-bond in the imines were estimated. The polarity of the C=N double bond in the imines was examined using a linear free-energy relationship. The idea of a thermodynamic characteristic graph (TCG) of imines as an efficient "Molecule ID Card" was introduced. The TCG can be used to quantitatively diagnose and predict the characteristic chemical properties of imines and their various reaction intermediates as well as the reduction mechanism of the imines. The information disclosed in this work could not only supply a gap of thermodynamics for the chemistry of imines but also strongly promote the fast development of the applications of imines.

  5. Iridium‐Catalyzed Condensation of Amines and Vicinal Diols to Substituted Piperazines

    Lorentz-Petersen, Linda Luise Reeh; Nordstrøm, Lars Ulrik Rubæk; Madsen, Robert

    2012-01-01

    is believed to involve dehydrogenation of the 1,2‐diol to the α‐hydroxy aldehyde, which condenses with the amine to form the α‐hydroxy imine. The latter rearranges to the corresponding α‐amino carbonyl compound, which then reacts with another amine followed by reduction of the resulting imine.......A straightforward procedure is described for the synthesis of piperazines from amines and 1,2‐diols. The heterocyclization is catalyzed by [Cp*IrCl2]2 and sodium hydrogen carbonate and can be achieved with either toluene or water as solvent. The transformation does not require any stoichiometric...

  6. An Efficient and Green Procedure for the Preparation of Acylals from ...

    An Efficient and Green Procedure for the Preparation of Acylals from Aldehydes Catalyzed by Alum [KAl(SO 4 ) 2 .12H 2 O] ... South African Journal of Chemistry ... mild reaction conditions, short reaction times and excellent yields, and offers a green synthetic solution by avoiding toxic catalysts and hazardous solvents.

  7. Purification of specific structured lipids by distillation: Effects on acyl migration

    Xu, Xuebing; Skands, A.; Adler-Nissen, Jens

    2001-01-01

    The cause and effects of acyl migration during the purification of specific structured lipids by distillation were studied in a conventional batch deodorizer with stripping steam. The mixture of specific structured lipids produced by lipase-catalyzed acidolysis between rapeseed oil and capric acid...... influenced the rate of acyl migration, and their combinations made the effect more severe. However, diacylglycerols were found to be the main reason for acyl migration. In the distillation of the specific structured lipid product mixture, distillation temperature and time were the main factors to determine...... the degree of acyl migration and the extent of separation of free fatty acids. The results indicate that more efficient separation technology should be used to improve the quality of the purified structured lipids. in order to reduce the distillation temperature, vacuum should be made as low as possible...

  8. Asymmetric and symmetric bolaform supra-amphiphiles: formation of imine bond influenced by aggregation.

    Wang, Guangtong; Wu, Guanglu; Wang, Zhiqiang; Zhang, Xi

    2014-02-18

    A series of bolaform supra-amphilphiles with different symmetries were fabricated through dynamic benzoic imine bond formation. The pH dependence of imine formations of these supra-amphiphiles were characterazied. We found that the extent of the imine formation of these supra-amphiphies were different. The supra-amphiphiles with a poorer symmetry always exhibited a lower imine formation at a given pH. Therefore, the varied extent of imine bond formation indicate the different aggregations of these supra-amphilphiles, which are controlled by the molecular symmetry of the supra-amphiphiles.

  9. Enhanced Ionic Conductivity of Poly(Ethylene Imine) Phosphate

    Senadeera, G.K.R.; Careem, M.A.; Skaarup, Steen

    1996-01-01

    The conductivity of mixtures of phosphoric acid with poly(ethylene imine) has been studied, and it was found that the conductivity of such mixtures with high acid content can be enhanced by the addition of highly dispersed silica (fumed silica). At the same time, silica addition increases the sti...

  10. Reactions of ethyl diazoacetate catalyzed by methylrhenium trioxide

    Zhu, Z.; Espenson, H. [Iowa State Univ., Ames, IA (United States)

    1995-11-03

    Methylrhenium trioxide (CH{sub 3}ReO{sub 3} or MTO) has found wise use in catalysis, including the epoxidation and metathesis of olefins, aldehyde olefination, and oxygen transfer. Extensive reports have now appeared in the area of MTO-catalyzed substrate oxidations with hydrogen peroxide. Certain catalytic applications of MTO for organic reactions that do not utilize peroxide have now been realized. In particular, a catalytic amount of MTO with ethyl diazoacetate (EDA) will convert aromatic imines to aziridines and convert aldehydes and ketones to epoxides. The aziridine preparation proceeds in high yields under anaerobic conditions more conveniently than with existing methods. Compounds with a three-membered heterocyclic ring can be obtained with the EDA/MTO catalytic system. Aromatic imines undergo cycloaddition reactions to give aziridines under mild conditions.

  11. Visible-light-promoted and one-pot synthesis of phenanthridines and quinolines from aldehydes and O-acyl hydroxylamine.

    An, Xiao-De; Yu, Shouyun

    2015-06-05

    A one-pot synthesis of phenanthridines and quinolines from commercially available or easily prepared aldehydes has been reported. O-(4-Cyanobenzoyl)hydroxylamine was utilized as the nitrogen source to generate O-acyl oximes in situ with aldehydes catalyzed by Brønsted acid. O-Acyl oximes were then subjected to visible light photoredox catalyzed cyclization via iminyl radicals to furnish aza-arenes. A variety of phenanthridines and quinolines have been prepared assisted by Brønsted acid and photocatalyst under visible light at room temperature with satisfactory yields.

  12. Cloning and characterization of human very-long-chain acyl-CoA dehydrogenase cDNA, chromosomal assignment of the gene and identification in four patients of nine different mutations within the VLCAD gene

    Andresen, B S; Bross, P; Vianey-Saban, C

    1996-01-01

    Very-long-chain acyl-CoA dehydrogenase (VLCAD) is one of four straight-chain acyl-CoA dehydrogenase (ACD) enzymes, which are all nuclear encoded mitochondrial flavoproteins catalyzing the initial step in fatty acid beta-oxidation. We have used the very fast, Rapid Amplification of cDNA Ends (RACE...

  13. Enantioselective N-Heterocyclic Carbene Catalysis via the Dienyl Acyl Azolium.

    Gillard, Rachel M; Fernando, Jared E M; Lupton, David W

    2018-04-16

    Herein we report the enantioselective N-heterocyclic carbene catalyzed (4+2) annulation of the dienyl acyl azolium with enolates. The reaction exploits readily accessible acyl fluorides and TMS enol ethers to give a range of highly enantio- and diastereo-enriched cyclohexenes (most >97:3 er and >20:1 dr). The reaction was found to require high nucleophilicity NHC catalysts with mechanistic studies supporting a stepwise 1,6-addition/β-lactonization. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Photoaffinity Labeling of Developing Jojoba Seed Microsomal Membranes with a Photoreactive Analog of Acyl-Coenzyme A (Acyl-CoA) (Identification of a Putative Acyl-CoA:Fatty Alcohol Acyltransferase.

    Shockey, J. M.; Rajasekharan, R.; Kemp, J. D.

    1995-01-01

    Jojoba (Simmondsia chinensis, Link) is the only plant known that synthesizes liquid wax. The final step in liquid wax biosynthesis is catalyzed by an integral membrane enzyme, fatty acyl-coenzyme A (CoA):fatty alcohol acyltransferase, which transfers an acyl chain from acyl-CoA to a fatty alcohol to form the wax ester. To purify the acyltransferase, we have labeled the enzyme with a radioiodinated, photoreactive analog of acyl-CoA, 12-[N-(4-azidosalicyl)amino] dodecanoyl-CoA (ASD-CoA). This molecule acts as an inhibitor of acyltransferase activity in the dark and as an irreversible inhibitor upon exposure to ultraviolet light. Oleoyl-CoA protects enzymatic activity in a concentration-dependent manner. Photolysis of microsomal membranes with labeled ASD-CoA resulted in strong labeling of two polypeptides of 57 and 52 kD. Increasing concentrations of oleoyl-CoA reduced the labeling of the 57-kD polypeptide dramatically, whereas the labeling of the 52-kD polypeptide was much less responsive to oleoyl-CoA. Also, unlike the other polypeptide, the labeling of the 57-kD polypeptide was enhanced considerably when photolyzed in the presence of dodecanol. These results suggest that a 57-kD polypeptide from jojoba microsomes may be the acyl-CoA:fatty alcohol acyltransferase.

  15. A combined mechanistic and computational study of the gold(I)-catalyzed formation of substituted indenes.

    Nun, Pierrick; Gaillard, Sylvain; Poater, Albert; Cavallo, Luigi; Nolan, Steven P

    2011-01-07

    Substituted indenes can be prepared after a sequence [1,3] O-acyl shift-hydroarylation-[1,3] O-acyl shift. Each step is catalyzed by a cationic NHC-Gold(I) species generated in situ after reaction between [(IPr)AuOH] and HBF(4)·OEt(2). This interesting silver-free way is fully supported by a computational study justifying the formation of each intermediate.

  16. An efficient and green synthesis of 1-indanone and 1-tetralone via intramolecular Friedel-Crafts acylation reaction

    Tran, Phuong Hoang; Huynh, Vy Hieu; Hansen, Poul Erik

    2015-01-01

    Metal-triflate-catalyzed intramolecular Friedel–Crafts acylation of 3-arylpropanoic and 4-arylbutanoic acids in triflate-anion ionic liquids under monomodal microwave irradiation is reported. The environmentally benign synthetic procedure allows the formation of cyclic ketones in good yields with...

  17. Synthesis and biological evaluation of triazole-containing N-acyl homoserine lactones as quorum sensing modulators

    Stacy, Danielle M.; Le Quement, Sebastian T.; Hansen, Casper L.

    2013-01-01

    triazole-containing analogs of natural N-acyl l-homoserine lactone (AHL) signals as non-native QS agonists and antagonists in Gram-negative bacteria. We synthesized 72 triazole derivatives of five broad structure types in high yields and purities using efficient Cu(i)-catalyzed azide–alkyne couplings...

  18. High Pressure Diels Alder Reactions of 1-Vinyl-2,2,6-trimethylcyclohexene Catalyzed by Chiral Lewis Acids; An Enantioselective Route to a Drimane Sesquiterpene Precursor.

    Knol, Joop; Meetsma, Auke; Feringa, Bernard

    1995-01-01

    The Diels Alder reaction of 1-vinyl-2,2,6-trimethylcyclohexene and 3-((E)-3-(methoxycarbonyl)propenoyl)-1,3-oxazolidin-2-one under high pressure, catalyzed by a chiral bis-imine copper(II) complex, yields a drimane sesquiterpene precursor in a highly regio- and diastereoselective manner with

  19. Pyridine synthesis by reactions of allyl amines and alkynes proceeding through a Cu(OAc)2 oxidation and Rh(III)-catalyzed N-annulation sequence.

    Kim, Dong-Su; Park, Jung-Woo; Jun, Chul-Ho

    2012-11-28

    A new methodology has been developed for the synthesis of pyridines from allyl amines and alkynes, which involves sequential Cu(II)-promoted dehydrogenation of the allylamine and Rh(III)-catalyzed N-annulation of the resulting α,β-unsaturated imine and alkyne.

  20. Unexpected Reaction Pathway for butyrylcholinesterase-catalyzed inactivation of “hunger hormone” ghrelin

    Yao, Jianzhuang; Yuan, Yaxia; Zheng, Fang; Zhan, Chang-Guo

    2016-02-01

    Extensive computational modeling and simulations have been carried out, in the present study, to uncover the fundamental reaction pathway for butyrylcholinesterase (BChE)-catalyzed hydrolysis of ghrelin, demonstrating that the acylation process of BChE-catalyzed hydrolysis of ghrelin follows an unprecedented single-step reaction pathway and the single-step acylation process is rate-determining. The free energy barrier (18.8 kcal/mol) calculated for the rate-determining step is reasonably close to the experimentally-derived free energy barrier (~19.4 kcal/mol), suggesting that the obtained mechanistic insights are reasonable. The single-step reaction pathway for the acylation is remarkably different from the well-known two-step acylation reaction pathway for numerous ester hydrolysis reactions catalyzed by a serine esterase. This is the first time demonstrating that a single-step reaction pathway is possible for an ester hydrolysis reaction catalyzed by a serine esterase and, therefore, one no longer can simply assume that the acylation process must follow the well-known two-step reaction pathway.

  1. Organocatalyzed α-Sulfenylation of carbonyl compounds using N-formly/Acyl Sulfenmides

    Noh, Hyeon Wan; Lee, Chan; Jang, Hye Young

    2017-01-01

    α-Sulfenylation of aldehydes and ketones using N-formyl and N-acyl sulfenamides, prepared by Cu-catalyzed aerobic coupling of amides and thiols, was achieved in the presence of cyclic secondary amine⋅HCl catalysts. To obtain various sulfur-functionalized carbonyl compounds, sulfenamides containing aromatic and aliphatic organosulfur were investigated. As carbonyl compounds, cyclic and acyclic ketones, 1,3-dicarbonyl compounds, and aldehydes were investigated, affording the desired α-sulfenylation products in good yields

  2. Organocatalyzed α-Sulfenylation of carbonyl compounds using N-formly/Acyl Sulfenmides

    Noh, Hyeon Wan; Lee, Chan; Jang, Hye Young [Dept. of Energy Systems Research, Ajou University, Suwon (Korea, Republic of)

    2017-03-15

    α-Sulfenylation of aldehydes and ketones using N-formyl and N-acyl sulfenamides, prepared by Cu-catalyzed aerobic coupling of amides and thiols, was achieved in the presence of cyclic secondary amine⋅HCl catalysts. To obtain various sulfur-functionalized carbonyl compounds, sulfenamides containing aromatic and aliphatic organosulfur were investigated. As carbonyl compounds, cyclic and acyclic ketones, 1,3-dicarbonyl compounds, and aldehydes were investigated, affording the desired α-sulfenylation products in good yields.

  3. Mechanism of Intramolecular Rhodium- and Palladium-Catalyzed Alkene Alkoxyfunctionalizations

    Vummaleti, Sai V. C.; Alghamdi, Miasser; Poater, Albert; Falivene, Laura; Scaranto, Jessica; Beetstra, Dirk J.; Morton, Jason G.; Cavallo, Luigi

    2015-01-01

    Density functional theory calculations have been used to investigate the reaction mechanism for the [Rh]-catalyzed intramolecular alkoxyacylation ([Rh] = [RhI(dppp)+] (dppp, 1,3-bis(diphenylphosphino)propane) and [Pd]/BPh3 dual catalytic system assisted intramolecular alkoxycyanation ([Pd] = Pd-Xantphos) using acylated and cyanated 2-allylphenol derivatives as substrates, respectively. Our results substantially confirm the proposed mechanism for both [Rh]- and [Pd]/ BPh3-mediated alkoxyfunctionalizations, offering a detailed geometrical and energetical understanding of all the elementary steps. Furthermore, for the [Rh]-mediated alkoxyacylation, our observations support the hypothesis that the quinoline group of the substrate is crucial to stabilize the acyl metal complex and prevent further decarbonylation. For [Pd]/BPh3-catalyzed alkoxycyanation, our findings clarify how the Lewis acid BPh3 cocatalyst accelerates the only slow step of the reaction, corresponding to the oxidative addition of the cyanate O-CN bond to the Pd center. © 2015 American Chemical Society.

  4. Mechanism of Intramolecular Rhodium- and Palladium-Catalyzed Alkene Alkoxyfunctionalizations

    Vummaleti, Sai V. C.

    2015-11-13

    Density functional theory calculations have been used to investigate the reaction mechanism for the [Rh]-catalyzed intramolecular alkoxyacylation ([Rh] = [RhI(dppp)+] (dppp, 1,3-bis(diphenylphosphino)propane) and [Pd]/BPh3 dual catalytic system assisted intramolecular alkoxycyanation ([Pd] = Pd-Xantphos) using acylated and cyanated 2-allylphenol derivatives as substrates, respectively. Our results substantially confirm the proposed mechanism for both [Rh]- and [Pd]/ BPh3-mediated alkoxyfunctionalizations, offering a detailed geometrical and energetical understanding of all the elementary steps. Furthermore, for the [Rh]-mediated alkoxyacylation, our observations support the hypothesis that the quinoline group of the substrate is crucial to stabilize the acyl metal complex and prevent further decarbonylation. For [Pd]/BPh3-catalyzed alkoxycyanation, our findings clarify how the Lewis acid BPh3 cocatalyst accelerates the only slow step of the reaction, corresponding to the oxidative addition of the cyanate O-CN bond to the Pd center. © 2015 American Chemical Society.

  5. Cytochrome c catalyzes the in vitro synthesis of arachidonoyl glycine

    McCue, Jeffrey M.; Driscoll, William J.; Mueller, Gregory P.

    2008-01-01

    Long chain fatty acyl glycines are an emerging class of biologically active molecules that occur naturally and produce a wide array of physiological effects. Their biosynthetic pathway, however, remains unknown. Here we report that cytochrome c catalyzes the synthesis of N-arachidonoyl glycine (NAGly) from arachidonoyl coenzyme A and glycine in the presence of hydrogen peroxide. The identity of the NAGly product was verified by isotope labeling and mass analysis. Other heme-containing proteins, hemoglobin and myoglobin, were considerably less effective in generating arachidonoyl glycine as compared to cytochrome c. The reaction catalyzed by cytochrome c in vitro points to its potential role in the formation of NAGly and other long chain fatty acyl glycines in vivo

  6. Reversal of diastereofacial selectivity in hydride reductions of N-tert-butanesulfinyl imines.

    Colyer, John T; Andersen, Neil G; Tedrow, Jason S; Soukup, Troy S; Faul, Margaret M

    2006-09-01

    A variety of N-tert-butanesulfinyl imines were reduced with NaBH4 in THF containing 2% water to provide the corresponding secondary sulfinamides in high yield and diastereoselectivity. By using the same sulfinyl imine starting materials and changing the reductant to L-Selectride, the stereoselectivity could be efficiently reversed to afford the opposite product diastereomer in high yield and selectivity.

  7. Generation of fatty acids by an acyl esterase in the bioluminescent system of Photobacterium phosphoreum

    Carey, L.M.; Rodriguez, A.; Meighen, E.

    1984-01-01

    The fatty acid reductase complex from Photobacterium phosphoreum has been discovered to have a long chain ester hydrolase activity associated with the 34K protein component of the complex. This protein has been resolved from the other components (50K and 58K) of the fatty acid reductase complex with a purity of > 95% and found to catalyze the transfer of acyl groups from acyl-CoA primarily to thiol acceptors with a low level of transfer to glycerol and water. Addition of the 50K protein of the complex caused a dramatic change in specificity increasing the transfer to oxygen acceptors. The acyl-CoA hydrolase activity increased almost 10-fold, and hence free fatty acids can be generated by the 34K protein when it is present in the fatty acid reductase complex. Hydrolysis of acyl-S-mercaptoethanol and acyl-1-glycerol and the ATP-dependent reduction of the released fatty acids to aldehyde for the luminescent reaction were also demonstrated for the reconstituted fatty acid reductase complex, raising the possibility that the immediate source of fatty acids for this reaction in vivo could be the membrane lipids and/or the fatty acid synthetase system

  8. Stearoyl-Acyl Carrier Protein and Unusual Acyl-Acyl Carrier Protein Desaturase Activities Are Differentially Influenced by Ferredoxin1

    Schultz, David J.; Suh, Mi Chung; Ohlrogge, John B.

    2000-01-01

    Acyl-acyl carrier protein (ACP) desaturases function to position a single double bond into an acyl-ACP substrate and are best represented by the ubiquitous Δ9 18:0-ACP desaturase. Several variant acyl-ACP desaturases have also been identified from species that produce unusual monoenoic fatty acids. All known acyl-ACP desaturase enzymes use ferredoxin as the electron-donating cofactor, and in almost all previous studies the photosynthetic form of ferredoxin rather than the non-photosynthetic form has been used to assess activity. We have examined the influence of different forms of ferredoxin on acyl-ACP desaturases. Using combinations of in vitro acyl-ACP desaturase assays and [14C]malonyl-coenzyme A labeling studies, we have determined that heterotrophic ferredoxin isoforms support up to 20-fold higher unusual acyl-ACP desaturase activity in coriander (Coriandrum sativum), Thunbergia alata, and garden geranium (Pelargonium × hortorum) when compared with photosynthetic ferredoxin isoforms. Heterotrophic ferredoxin also increases activity of the ubiquitous Δ9 18:0-ACP desaturase 1.5- to 3.0-fold in both seed and leaf extracts. These results suggest that ferredoxin isoforms may specifically interact with acyl-ACP desaturases to achieve optimal enzyme activity and that heterotrophic isoforms of ferredoxin may be the in vivo electron donor for this reaction. PMID:11027717

  9. Stearoyl-acyl carrier protein and unusual acyl-acyl carrier protein desaturase activities are differentially influenced by ferredoxin.

    Schultz, D J; Suh, M C; Ohlrogge, J B

    2000-10-01

    Acyl-acyl carrier protein (ACP) desaturases function to position a single double bond into an acyl-ACP substrate and are best represented by the ubiquitous Delta9 18:0-ACP desaturase. Several variant acyl-ACP desaturases have also been identified from species that produce unusual monoenoic fatty acids. All known acyl-ACP desaturase enzymes use ferredoxin as the electron-donating cofactor, and in almost all previous studies the photosynthetic form of ferredoxin rather than the non-photosynthetic form has been used to assess activity. We have examined the influence of different forms of ferredoxin on acyl-ACP desaturases. Using combinations of in vitro acyl-ACP desaturase assays and [(14)C]malonyl-coenzyme A labeling studies, we have determined that heterotrophic ferredoxin isoforms support up to 20-fold higher unusual acyl-ACP desaturase activity in coriander (Coriandrum sativum), Thunbergia alata, and garden geranium (Pelargonium x hortorum) when compared with photosynthetic ferredoxin isoforms. Heterotrophic ferredoxin also increases activity of the ubiquitous Delta9 18:0-ACP desaturase 1.5- to 3.0-fold in both seed and leaf extracts. These results suggest that ferredoxin isoforms may specifically interact with acyl-ACP desaturases to achieve optimal enzyme activity and that heterotrophic isoforms of ferredoxin may be the in vivo electron donor for this reaction.

  10. Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme.

    Wang, Nan; Rudolf, Jeffrey D; Dong, Liao-Bin; Osipiuk, Jerzy; Hatzos-Skintges, Catherine; Endres, Michael; Chang, Chin-Yuan; Babnigg, Gyorgy; Joachimiak, Andrzej; Phillips, George N; Shen, Ben

    2018-06-04

    Acyl-coenzyme A (CoA) ligases catalyze the activation of carboxylic acids via a two-step reaction of adenylation followed by thioesterification. Here, we report the discovery of a non-adenylating acyl-CoA ligase PtmA2 and the functional separation of an acyl-CoA ligase reaction. Both PtmA1 and PtmA2, two acyl-CoA ligases from the biosynthetic pathway of platensimycin and platencin, are necessary for the two steps of CoA activation. Gene inactivation of ptmA1 and ptmA2 resulted in the accumulation of free acid and adenylate intermediates, respectively. Enzymatic and structural characterization of PtmA2 confirmed its ability to only catalyze thioesterification. Structural characterization of PtmA2 revealed it binds both free acid and adenylate substrates and undergoes the established mechanism of domain alternation. Finally, site-directed mutagenesis restored both the adenylation and complete CoA activation reactions. This study challenges the currently accepted paradigm of adenylating enzymes and inspires future investigations on functionally separated acyl-CoA ligases and their ramifications in biology.

  11. Interesterification of rapeseed oil catalyzed by tin octoate

    Galia, Alessandro; Centineo, Alessio; Saracco, Guido; Schiavo, Benedetto; Scialdone, Onofrio

    2014-01-01

    The interesterification of rapeseed oil was performed for the first time by using tin octoate as Lewis acid homogeneous catalysts and methyl or ethyl acetate as acyl acceptors in a batch reactor, within the temperature range 393–483 K. The yields in fatty acid ethyl esters (FAEE) and triacetin (TA) after 20 h of reaction time increased from 8% and 2%–to 61% and 22%, respectively, when the reaction temperature increased from 423 to 483 K. An optimum value of 40 for the acyl acceptor to oil molar ratio was found to be necessary to match good fatty acid alkyl ester yields with high enough reaction rate. The rate of generation of esters was significantly higher when methyl acetate was used as acyl acceptor instead of its ethyl homologue. The collected results suggest that tin octoate can be used as effective catalyst for the interesterification of rapeseed oil with methyl or ethyl acetate being highly soluble in the reaction system, less expensive than enzymes and allowing the operator to work under milder conditions than supercritical interesterification processes. - Highlights: • We study the interesterification of rapeseed oil catalyzed by tin(II) octoate. • Tin(II) octoate is an effective homogeneous catalyst at 483 K. • The acyl acceptor to oil molar ratio must be optimized. • Higher rate of reaction is obtained with methyl acetate as acyl acceptor

  12. Supercritical CO2 as a reaction medium for synthesis of capsaicin analogues by lipase-catalyzed transacylation of capsaicin.

    Kobata, Kenji; Kobayashi, Mamiko; Kinpara, Sachiyo; Watanabe, Tatsuo

    2003-09-01

    Capsaicin analogues having different acyl moiety were synthesized by lipase-catalyzed transacylation of capsaicin with a corresponding acyl donor in supercritical CO2 as a reaction medium. Transacylation with methyl tetradecanoate using Novozym 435 as a catalyst gave vanillyl tetradecanamide in a 54% yield at 80 degrees C and 19 MPa over 72 h. Vanillyl (Z)-9-octadecenamide, olvanil, was synthesized from triolein in a 21% yield over 7 d.

  13. NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones.

    Takaki, Ken; Hino, Makoto; Ohno, Akira; Komeyama, Kimihiro; Yoshida, Hiroto; Fukuoka, Hiroshi

    2017-01-01

    Thiazolium carbene-catalyzed reactions of 1,2-diketones and 1,2,3-triketones with enones and ynones have been investigated. The diketones gave α,β-double acylation products via unique Breslow intermediates isolable as acid salts, whereas the triketones formed stable adducts with the NHC instead of the coupling products.

  14. NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones

    Ken Takaki

    2017-08-01

    Full Text Available Thiazolium carbene-catalyzed reactions of 1,2-diketones and 1,2,3-triketones with enones and ynones have been investigated. The diketones gave α,β-double acylation products via unique Breslow intermediates isolable as acid salts, whereas the triketones formed stable adducts with the NHC instead of the coupling products.

  15. Acyl-CoA metabolism and partitioning

    Grevengoed, Trisha J; Klett, Eric L; Coleman, Rosalind A

    2014-01-01

    Long-chain fatty acyl-coenzyme As (CoAs) are critical regulatory molecules and metabolic intermediates. The initial step in their synthesis is the activation of fatty acids by one of 13 long-chain acyl-CoA synthetase isoforms. These isoforms are regulated independently and have different tissue...

  16. Acylated flavone glycosides from Veronica

    Albach, Dirk C.; Grayer, Renée J.; Jensen, Søren Rosendal

    2003-01-01

    A survey of the flavonoid glycosides of selected taxa in the genus Veronica yielded two new acylated 5,6,7,3',4'-pentahydroxyflavone (6-hydroxyluteolin) glycosides and two rare allose-containing acylated 5,7,8,4'-tetrahydroxyflavone (isoscutellarein) glycosides. The new compounds were isolated from...

  17. A Convenient Synthesis of Conjugated Acetylenic Ketones by Copper(l)-Catalyzed under Microwave Irradiation

    WANG JinXian; WEI BangGuo; ZHAO LianBiao; HU YuLai; KANG LiQing

    2001-01-01

    @@ Alkynyl ketones are useful precursors and intermediates in synthetic organic chemistry1 and has evoked considerable interest. A number of methods for the synthesis of conjugated acetylenic ketones involve the reaction a metal acetylide with an acyl chlorides or another carboxylic acid derivative have been developed 2. Recently, the synthesis of α, β-conjugated acetylenic ketones catalyzed by Pd(Ⅱ) or by copper(Ⅰ)pd(Ⅱ) reaction of 1-alkynes and acyl chlorides have been described. The acylation of terminal alkynes by acyl chlorides in the presence of catalytic amounts copper(Ⅰ) salts leading to α, β-conjugated acetylenic ketones has also been reported. However, many of these reactions suffer from lack of high pressure (17 atm), long reaction time (30 h)and require low temperatures (-78℃). Our work involves the synthesis of conjugated acetylenic ketones via the reaction of terminal alkynes with aroyl chlorides in the presence of cuprous iodide under microwave irradiation conditions.

  18. Occurrence of cyclic imines in European commercial seafood and consumers risk assessment

    Rambla-Alegre, Maria; Miles, Christopher O.; de la Iglesia, Pablo

    2018-01-01

    Cyclic imines constitute a quite recently discovered group of marine biotoxins that act on neural receptors and that bioaccumulate in seafood. They are grouped together due to the imino group functioning as their common pharmacore, responsible for acute neurotoxicity in mice. Cyclic imines (CIs...... countries (Italy, Portugal, Slovenia, Spain, Ireland, Norway, The Netherlands and Denmark) were obtained over 2 years. Emerging cyclic imine concentrations in all the samples were analysed on a LC-3200QTRAP and LC-HRMS QExactive mass spectrometer. In shellfish, two CIs, pinnatoxin G (PnTX-G) and 13...

  19. Semi-catalytic reduction of secondary amides to imines and aldehydes.

    Lee, Sun-Hwa; Nikonov, Georgii I

    2014-06-21

    Secondary amides can be reduced by silane HSiMe2Ph into imines and aldehydes by a two-stage process involving prior conversion of amides into iminoyl chlorides followed by catalytic reduction mediated by the ruthenium complex [Cp(i-Pr3P)Ru(NCCH3)2]PF6 (1). Alkyl and aryl amides bearing halogen, ketone, and ester groups were converted with moderate to good yields under mild reaction conditions to the corresponding imines and aldehydes. This procedure does not work for substrates bearing the nitro-group and fails for heteroaromatic amides. In the case of cyano substituted amides, the cyano group is reduced to imine.

  20. Thermal, structural and electrochemical properties of new aliphatic-aromatic imine with piperazine moieties blended with titanium dioxide

    Różycka, Anna; Fryń, Patryk; Iwan, Agnieszka; Bogdanowicz, Krzysztof Artur; Filapek, Michal; Górska, Natalia; Dąbczyński, Paweł; Rysz, Jakub; Pociecha, Damian; Hreniak, Agnieszka; Marzec, Monika

    2018-02-01

    A new piperazine imine, (7E)-N-((4-((E)-(4-hexadecylphenylimino)methyl)piperazin-1-yl)methylene)-4-dodecylbenzenamine, has been synthesized by the condensation of 1,4-piperazinedicarboxaldehyde with 4-hexadecylaniline. The imine was characterized by cyclic voltammetry, Fourier transform middle-infrared absorption spectroscopy and X-ray diffraction. Thermal properties of imine was analyzed by differential scanning calorimetry method during first and second heating scan at 10 and 20 °C/min. Texture of imine was investigated by polarized optical microscopy and atomic force microscopy. Furthermore, imine was blended with titanium dioxide in anatase form and fully characterized by the same methods. Piperazine imine and its mixture with titanium dioxide exhibited only a transition from crystal to isotropic state. Imine exhibits two-step reduction wave attributed to one-electron transfer in each step as was found by cyclic voltammetry. Both titanium dioxide and poly(3-hexylthiophene) change the electrochemical properties of piperazine imine, however, in different ways. Studied imine blended with titanium dioxide exhibited higher value of energy band gap than pure piperazine imine and lower Eg than pure poly(3-hexylthiophene).

  1. An insight on acyl migration in solvent-free ethanolysis of model triglycerides using Novozym 435.

    Sánchez, Daniel Alberto; Tonetto, Gabriela Marta; Ferreira, María Luján

    2016-02-20

    In this work, the ethanolysis of triglycerides catalyzed by immobilized lipase was studied, focusing on the secondary reaction of acyl migration. The catalytic tests were performed in a solvent-free reaction medium using Novozym 435 as biocatalyst. The selected experimental variables were biocatalyst loading (5-20mg), reaction time (30-90min), and chain length of the fatty acids in triglycerides with and without unsaturation (short (triacetin), medium (tricaprylin) and long (tripalmitin/triolein)). The formation of 2-monoglyceride by ethanolysis of triglycerides was favored by long reaction times and large biocatalyst loading with saturated short- to medium-chain triglycerides. In the case of long-chain triglycerides, the formation of this monoglyceride was widely limited by acyl migration. In turn, acyl migration increased the yield of ethyl esters and minimized the content of monoglycerides and diglycerides. Thus, the enzymatic synthesis of biodiesel was favored by long-chain triglycerides (which favor the acyl migration), long reaction times and large biocatalyst loading. The conversion of acylglycerides made from long-chain fatty acids with unsaturation was relatively low due to limitations in their access to the active site of the lipase. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Friedel-Crafts Acylation with Amides

    Raja, Erum K.; DeSchepper, Daniel J.; Nilsson Lill, Sten O.; Klumpp, Douglas A.

    2012-01-01

    Friedel-Crafts acylation has been known since the 1870s and it is an important organic synthetic reaction leading to aromatic ketone products. Friedel-Crafts acylation is usually done with carboxylic acid chlorides or anhydrides while amides are generally not useful substrates in these reactions. Despite being the least reactive carboxylic acid derivative, we have found a series of amides capable of providing aromatic ketones in good yields (55–96%, 17 examples). We propose a mechanism involving diminished C-N resonance through superelectrophilic activation and subsequent cleavage to acyl cations. PMID:22690740

  3. Identification of quinone imine containing glutathione conjugates of diclofenac in rat bile.

    Waldon, Daniel J; Teffera, Yohannes; Colletti, Adria E; Liu, Jingzhou; Zurcher, Danielle; Copeland, Katrina W; Zhao, Zhiyang

    2010-12-20

    High-resolution accurate MS with an LTQ-Orbitrap was used to identify quinone imine metabolites derived from the 5-hydroxy (5-OH) and 4 prime-hydroxy (4'-OH) glutathione conjugates of diclofenac in rat bile. The initial quinone imine metabolites formed by oxidation of diclofenac have been postulated to be reactive intermediates potentially involved in diclofenac-mediated hepatotoxicity; while these metabolites could be formed using in vitro systems, they have never been detected in vivo. This report describes the identification of secondary quinone imine metabolites derived from 5-OH and 4'-OH diclofenac glutathione conjugates in rat bile. To verify the proposed structures, the diclofenac quinone imine GSH conjugate standards were prepared synthetically and enzymatically. The novel metabolite peaks displayed the identical retention times, accurate mass MS/MS spectra, and the fragmentation patterns as the corresponding authentic standards. The formation of these secondary quinone metabolites occurs only under conditions where bile salt homeostasis was experimentally altered. Standard practice in biliary excretion experiments using bile duct-cannulated rats includes infusion of taurocholic acid and/or other bile acids to replace those lost due to continuous collection of bile; for this experiment, the rats received no replacement bile acid infusion. High-resolution accurate mass spectrometry data and comparison with chemically and enzymatically prepared quinone imines of diclofenac glutathione conjugates support the identification of these metabolites. A mechanism for the formation of these reactive quinone imine containing glutathione conjugates of diclofenac is proposed.

  4. Visible Light Induced Green Transformation of Primary Amines to Imines Using a Silicate Supported Anatase Photocatalyst

    Sifani Zavahir

    2015-01-01

    Full Text Available Catalytic oxidation of amine to imine is of intense present interest since imines are important intermediates for the synthesis of fine chemicals, pharmaceuticals, and agricultural chemicals. However, considerable efforts have been made to develop efficient methods for the oxidation of secondary amines to imines, while little attention has until recently been given to the oxidation of primary amines, presumably owing to the high reactivity of generated imines of primary amines that are easily dehydrogenated to nitriles. Herein, we report the oxidative coupling of a series of primary benzylic amines into corresponding imines with dioxygen as the benign oxidant over composite catalysts of TiO2 (anatase-silicate under visible light irradiation of λ > 460 nm. Visible light response of this system is believed to be as a result of high population of defects and contacts between silicate and anatase crystals in the composite and the strong interaction between benzylic amine and the catalyst. It is found that tuning the intensity and wavelength of the light irradiation and the reaction temperature can remarkably enhance the reaction activity. Water can also act as a green medium for the reaction with an excellent selectivity. This report contributes to the use of readily synthesized, environmentally benign, TiO2 based composite photocatalyst and solar energy to realize the transformation of primary amines to imine compounds.

  5. Visible light induced green transformation of primary amines to imines using a silicate supported anatase photocatalyst.

    Zavahir, Sifani; Zhu, Huaiyong

    2015-01-26

    Catalytic oxidation of amine to imine is of intense present interest since imines are important intermediates for the synthesis of fine chemicals, pharmaceuticals, and agricultural chemicals. However, considerable efforts have been made to develop efficient methods for the oxidation of secondary amines to imines, while little attention has until recently been given to the oxidation of primary amines, presumably owing to the high reactivity of generated imines of primary amines that are easily dehydrogenated to nitriles. Herein, we report the oxidative coupling of a series of primary benzylic amines into corresponding imines with dioxygen as the benign oxidant over composite catalysts of TiO2 (anatase)-silicate under visible light irradiation of λ > 460 nm. Visible light response of this system is believed to be as a result of high population of defects and contacts between silicate and anatase crystals in the composite and the strong interaction between benzylic amine and the catalyst. It is found that tuning the intensity and wavelength of the light irradiation and the reaction temperature can remarkably enhance the reaction activity. Water can also act as a green medium for the reaction with an excellent selectivity. This report contributes to the use of readily synthesized, environmentally benign, TiO2 based composite photocatalyst and solar energy to realize the transformation of primary amines to imine compounds.

  6. Structural organization of the human short-chain acyl-CoA dehydrogenase gene

    Corydon, M J; Andresen, B S; Bross, P

    1997-01-01

    Short-chain acyl-CoA dehydrogenase (SCAD) is a homotetrameric mitochondrial flavoenzyme that catalyzes the initial reaction in short-chain fatty acid beta-oxidation. Defects in the SCAD enzyme are associated with failure to thrive, often with neuromuscular dysfunction and elevated urinary excretion...... shown to be associated with ethylmalonic aciduria. From analysis of 18 unrelated Danish families, we show that the four SCAD gene polymorphisms constitute five allelic variants of the SCAD gene, and that the 625A variant together with the less frequent variant form of the three other polymorphisms (321C....... The evolutionary relationship between SCAD and five other members of the acyl-CoA dehydrogenase family was investigated by two independent approaches that gave similar phylogenetic trees....

  7. Regiospecific synthesis of new fatty N-acyl trihalomethylated pyrazoline derivatives from fatty acid methyl esters (FAMEs)

    Beck, Paulo; Santos, Juliane M. dos; D' Oca, Marcelo G. M.; Piovesan, Luciana A., E-mail: lpiovesan@gmail.com [Universidade Federal do Rio Grande (UFRS), RS (Brazil). Escola de Quimica e Alimentos; Kuhn, Bruna L.; Moreira, Dayse N.; Flores, Alex F.C.; Martins, Marcos A.P. [Universidade Federal de Santa Maria (UFSM), RS (Brazil). Dept. de Quimica

    2012-11-15

    A series of new fatty N-acyl trihalomethylated pyrazoline derivatives from fatty acid methyl esters was synthesized by the cyclo condensation of respective fatty hydrazides with 4-alkoxy- 1,1,1-trial omethyl-3-alquen-2-ones. Efficient and regiospecific cyclizations catalyzed by BF{sub 3}-MeOH gave the desired products in good to excellent yields and at high purity. (author)

  8. Synthesis, Characterisation and DFT Calculations of Azo-Imine Dyes

    Sevil Özkınalı

    2017-11-01

    Full Text Available In this study, azo dyes containing an imine group were synthesised by coupling p-hydroxybenzylidene aniline with the diazonium salts of p-toluidine, 4-aminophenol, aniline, p-chloroaniline, p-fluoroaniline, and p-nitroaniline. The compounds were characterised by melting point, elemental, UV-Vis and IR analyses as well as 1H-NMR and 13C-NMR spectroscopies. Moreover, the experimental data were supplemented with density functional theory (DFT calculations. The experimental data on FT-IR and UV–Vis spectra of the compounds were compared with theoretical results. The DFT calculations were performed to obtain the ground state geometries of the compounds using the B3LYP hybrid functional level with 6-311++g(2d,2p basis set. Frontier molecular orbital energies, band gap energies and some chemical reactivity parameters, such as chemical hardness and electronegativity, were calculated and compared with experimental values. A significant correlation was observed between the dipole moment and polarities of the solvents and the absorption wavelength of the compounds.

  9. ASSOCIATION OF BRANCHED POLYETHYLENE IMINE WITH SURFACTANTS IN AQUEOUS SOLUTION

    Ismael C. Bellettini

    2015-07-01

    Full Text Available Three polymer-surfactant systems comprised of branched polyethylene imine (PEI with an anionic surfactant (sodium dodecylsulfate; SDS, a cationic surfactant (tetradecyltrimethylammonium bromide; TTAB, and a zwitterionic surfactant (N-tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate; SB3-14 were studied based on the properties of surface tension, pyrene fluorescence emission, dynamic light scattering, pH, and zeta potential measurements. The critical aggregation concentration (cac and polymer saturation point (psp were determined for all three systems. The effect of these surfactants on the physico-chemical characteristics (diameter and surface charge of the complexes formed was determined. Polymer-surfactant interactions occurred in all of the systems studied, with the strongest interactions, electrostatic in nature, occurring in the SDS-PEI system. After the neutralization of the polymer charges with the addition of the surfactant, the hydrophobic effect started to control the interlacing of the polymer chains. For the PEI-TTAB system, a very dense film was formed at surfactant concentrations above 2.0 mmol L-1. In this case, the bromide counter-ion interacted with both the positively-charged PEI and the head of the surfactant, which is responsible for the formation of double layer coordination complexes. For the system composed of PEI and the zwitterionic surfactant, less cooperative associations occurred in comparison with the other systems.

  10. Thermally Stable Heterocyclic Imines as New Potential Nonlinear Optical Materials

    Nesterov, Volodymyr V.; Antipin, Mikhail Y.; Nesterov, Vladimir N.; Moore, Craig E.; Cardelino, Beatriz H.; Timofeeva, Tatiana V.

    2004-01-01

    In the course of a search for new thermostable acentric nonlinear optical crystalline materials, several heterocyclic imine derivatives were designed, with the general structure D-pi-A(D'). Introduction of a donor amino group (D') into the acceptor moiety was expected to bring H-bonds into their crystal structures, and so to elevate their melting points and assist in an acentric molecular packing. Six heterocycle-containing compounds of this type were prepared, single crystals were grown for five of them, and these crystals were characterized by X-ray analysis. A significant melting temperature elevation was found for all of the synthesized compounds. Three of the compounds were also found to crystallize in acentric space groups. One of the acentric compounds is built as a three-dimensional H-bonded molecular network. In the other two compounds, with very similar molecular structure, the molecules form one-dimensional H-bonded head-to-head associates (chains). These chains are parallel in two different crystallographic directions and form very unusual interpenetrating chain patterns in an acentric crystal. Two of the compounds crystallized with centrosymmetric molecular packing.

  11. Muoniated acyl and thioacyl radicals

    McKenzie, Iain; Brodovitch, Jean-Claude; Ghandi, Khashayar; Percival, Paul W.

    2006-01-01

    The product of the reaction of muonium with tert-butylisocyanate was previously assigned as the muoniated tert-butylaminyl radical (I. McKenzie, J.-C. Brodovitch, K. Ghandi, S. Kecman, P. W. Percival, Physica B 326 (2003) 76). This assignment is incorrect since the muon and 14 N hyperfine-coupling constants (hfcc) of this radical would have the opposite sign, which is in conflict with the experimental results. The radical is now reassigned as the muoniated N-tert-butylcarbamoyl radical, based on the similarities between the experimental muon and 14 N hfcc and hfcc calculated at the UB3LYP/6-311G(d,p)//UB3LYP/EPR-III level. The large zero-point energy in the N-Mu bond results in the dissociation barrier of the muoniated N-tert-butylcarbamoyl radical being above the combined energy of the reactants, in contrast to the N-tert-butylcarbamoyl radical where the dissociation barrier lies below the combined energy of the reactants. The reaction of muonium with tert-butylisothiocyanate produced both conformers of the muoniated N-tert-butylthiocarbamoyl radical and their assignment was based on the similarities between the experimental and calculated muon hfcc. These are the first acyl and thioacyl radicals to be directly detected by muon spin spectroscopy

  12. Muoniated acyl and thioacyl radicals

    McKenzie, Iain [TRIUMF and Department of Chemistry, 8888 University Drive, Simon Fraser University, Burnaby B.C., V5A 1S6 (Canada); Brodovitch, Jean-Claude [TRIUMF and Department of Chemistry, 8888 University Drive, Simon Fraser University, Burnaby B.C., V5A 1S6 (Canada); Ghandi, Khashayar [TRIUMF and Department of Chemistry, 8888 University Drive, Simon Fraser University, Burnaby B.C., V5A 1S6 (Canada); Percival, Paul W. [TRIUMF and Department of Chemistry, 8888 University Drive, Simon Fraser University, Burnaby B.C., V5A 1S6 (Canada)]. E-mail: percival@sfu.ca

    2006-03-31

    The product of the reaction of muonium with tert-butylisocyanate was previously assigned as the muoniated tert-butylaminyl radical (I. McKenzie, J.-C. Brodovitch, K. Ghandi, S. Kecman, P. W. Percival, Physica B 326 (2003) 76). This assignment is incorrect since the muon and {sup 14}N hyperfine-coupling constants (hfcc) of this radical would have the opposite sign, which is in conflict with the experimental results. The radical is now reassigned as the muoniated N-tert-butylcarbamoyl radical, based on the similarities between the experimental muon and {sup 14}N hfcc and hfcc calculated at the UB3LYP/6-311G(d,p)//UB3LYP/EPR-III level. The large zero-point energy in the N-Mu bond results in the dissociation barrier of the muoniated N-tert-butylcarbamoyl radical being above the combined energy of the reactants, in contrast to the N-tert-butylcarbamoyl radical where the dissociation barrier lies below the combined energy of the reactants. The reaction of muonium with tert-butylisothiocyanate produced both conformers of the muoniated N-tert-butylthiocarbamoyl radical and their assignment was based on the similarities between the experimental and calculated muon hfcc. These are the first acyl and thioacyl radicals to be directly detected by muon spin spectroscopy.

  13. Production of structured lipids: acyl migration during enzymatic interesterification and downstream processing

    Xu, Xuebing

    1997-01-01

    Production of structured lipids by lipase-catalyzed interesterification attracts great interests recently. Structured lipids are defined, in this article, as triacylglycerols which contain both medium or short chain fatty acids and long chain fatty acids, each groups locating specifically in the sn......-2 position or sn-1,3 positions of glycerol backbone. These kinds of lipids are reported to be promising for both enteral and parenteral nutrition. However, acyl migration occurs in the reaction stage and downstream purification process. This side-reaction causes by-products which are harmful...

  14. Interaction of gamma-glutamyltranspeptidase with clofibryl-S-acyl-glutathione in vitro and in vivo in rat.

    Grillo, M P; Benet, L Z

    2001-08-01

    Clofibric acid (CA) is metabolized to chemically reactive acylating products that can transacylate glutathione to form clofibryl-S-acyl-glutathione (CA-SG) in vitro and in vivo. We investigated the first step in the degradation of CA-SG to the mercapturic acid conjugate, clofibryl-S-acyl-N-acetylcysteine (CA-SNAC), which is catalyzed by gamma-glutamyltranspeptidase (gamma-GT). After gamma-GT mediated cleavage of glutamate from CA-SG, the product clofibryl-S-acyl-cysteinylglycine (CA-S-CG) should undergo an intramolecular rearrangement reaction [Tate, S. S. (1975) FEBS Lett. 54, 319-322] to form clofibryl-N-acyl-cysteinylglycine (CA-N-CG). We performed in vitro studies incubating CA-SG with gamma-GT to determine the products formed, and in vivo studies examining the products excreted in urine after dosing rats with CA-SG or CA. Thus, CA-SG (0.1 mM) was incubated with gamma-GT (0.1 unit/mL) in buffer (pH 7.4, 25 degrees C) and analyzed for products formed by reversed-phase HPLC and electrospray mass spectrometry (ESI/MS). Results showed that CA-SG is degraded completely after 6 h of incubation leading to the formation of two products, CA-N-CG and its disulfide, with no detection of CA-S-CG thioester. After 36 h of incubation, only the disulfide remained in the incubation. Treatment of the disulfide with dithiothreitol led to the reappearance of CA-N-CG. ESI/LC/MS analysis of urine (16 h) extracts of CA-SG-dosed rats (200 mg/kg, iv) showed that CA-SG is degraded to CA-N-CG, CA-N-acyl-cysteine (CA-N-C) and their respective S-methylated products. The mercapturic acid conjugate (CA-SNAC) was found as a minor product. Analysis of urine extracts from CA-dosed rats (200 mg/kg, ip) resulted in the detection of clofibryl-N-acyl-cysteine (CA-N-C), but no evidence for the formation of CA-SNAC was obtained. These in vitro and in vivo experiments indicate that gamma-GT mediated degradation of clofibryl-S-acyl-glutathione leads primarily to the formation and excretion of clofibryl-N-acyl

  15. Syntheses of Azo-Imine Derivatives from Vanillin as an Acid Base Indicator

    Bambang Purwono

    2013-05-01

    Full Text Available Preparations of azo, imine and azo-imine derivatives from vanillin as an indicator of acid-base titration have been carried out. The azo derivative of 4-hydroxy-3-methoxy-5-(phenylazobenzaldehyde 2 was produced by diazotitation reaction of vanillin in 37.04% yield. The azo product was then refluxed with aniline in ethanol to yield azo-imine derivatives, 2-methoxy-6-(phenylazo-4-((phenyliminomethylphenol 1 in 82.21% yield. The imine derivative, 2-methoxy-4-((phenyliminomethyl-phenol 3 was obtained by refluxing of vanillin and aniline mixture in ethanol solvent and produced 82.17% yield. The imine product was then reacted with benzenediazonium chloride salt. However, the products indicated hydrolyzed product of 4-hydroxy-3-methoxy-5-(phenylazobenzaldehyde 2 in 22.15% yield. The 2-methoxy-4-((phenyliminomethylphenol 2 could be used as an indicator for titration of NaOH by H2C2O4 with maximum concentration of H2C2O4 0.1 M while the target compound 1 could be used as titration indicator for titration of NaOH with H2C2O4 with same result using phenolphthalein indicator.

  16. Sequential one-pot synthesis of imidazoles and 2H-imidazolones from β-ketoamines, acylating agents and ammonium acetate

    Jalani, Hitesh B.; Venkateswararao, Edda; Manickam, Manoj; Jung, Sang Hun [College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon (Korea, Republic of)

    2016-12-15

    An efficient, practical, straight forward, and transition metal-free three-component synthesis of diversely substituted imidazoles and 2H-imidazolones from β-ketoamines, acylating agents, and ammonium acetate has been described herein. This approach involves [3+1+1] cyclization through consecutive formation of three C–N bonds as a sequence of initial amidation of β-ketoamines with acylating agent, β-iminoketoamide formation with ammonia, and acid catalyzed concomitant cyclodehydration to afford the imidazoles and 2H-imidazolones. This methodology has advantages such as single flask operation, readily available starting materials, mild conditions, broad functional groups tolerance, and simple work-up procedure.

  17. Parameters affecting incorporation and by-product formation during the production of structured phospholipids by lipase-catalyzed acidolysis in solvent free system

    Vikbjerg, Anders Falk; Mu, Huiling; Xu, Xuebing

    2005-01-01

    By-product formation is a serious problem in the lipase-catalyzed acyl exchange of phospholipids (PL). By-products are formed due to parallel hydrolysis reactions and acyl migration in the reaction system. A clear elucidation of these side reactions is important for practical operation in order...... to minimize by-products during reaction. In the present study we examined the Lipozyme RM IM-catalyzed acidolysis for the production of structured phospholipids between phosphatidylcholine (PC) and caprylic acid in the solvent free system. A five-factor response surface design was used to evaluate...

  18. Catalyzing RE Project Development

    Anderson, Kate; Elgqvist, Emma; Walker, Andy; Cutler, Dylan; Olis, Dan; DiOrio, Nick; Simpkins, Travis

    2016-09-01

    This poster details how screenings done with REopt - NREL's software modeling platform for energy systems integration and optimization - are helping to catalyze the development of hundreds of megawatts of renewable energy.

  19. RuO4-mediated oxidation of secondary amines 2. imines as main reaction intermediates

    Florea Cristina A.

    2017-01-01

    Full Text Available Oxidation by RuO4 (generated in situ from RuO2 and NaIO4 of secondary amines such as Bn–NH–CH2R (1; R=H, Me gave complex reaction mixtures, but mainly amides. In the presence of cyanide, the leading products were α-aminonitriles. Comparison of the oxidation products of 1 with those from the corresponding imines PhCH=N–CH2R and Bn–N=CH–R showed that formation of the indicated imines is the first main step in the oxidation of 1. A detailed mechanism is proposed.

  20. Development of an activity-based probe for acyl-protein thioesterases

    Garland, Megan; Schulze, Christopher J.; Foe, Ian T.; van der Linden, Wouter A.; Child, Matthew A.

    2018-01-01

    Protein palmitoylation is a dynamic post-translational modification (PTM) important for cellular functions such as protein stability, trafficking, localization, and protein-protein interactions. S-palmitoylation occurs via the addition of palmitate to cysteine residues via a thioester linkage, catalyzed by palmitoyl acyl transferases (PATs), with removal of the palmitate catalyzed by acyl protein thioesterases (APTs) and palmitoyl-protein thioesterases (PPTs). Tools that target the regulators of palmitoylation–PATs, APTs and PPTs–will improve understanding of this essential PTM. Here, we describe the synthesis and application of a cell-permeable activity-based probe (ABP) that targets APTs in intact mammalian cells and the parasite Toxoplasma gondii. Using a focused library of substituted chloroisocoumarins, we identified a probe scaffold with nanomolar affinity for human APTs (HsAPT1 and HsAPT2) and synthesized a fluorescent ABP, JCP174-BODIPY TMR (JCP174-BT). We use JCP174-BT to profile HsAPT activity in situ in mammalian cells, to detect an APT in T. gondii (TgPPT1). We show discordance between HsAPT activity levels and total protein concentration in some cell lines, indicating that total protein levels may not be representative of APT activity in complex systems, highlighting the utility of this probe. PMID:29364904

  1. Selectivity control in pd-catalyzed c-h functionalization reactions

    Flores Gaspar, Areli

    2013-01-01

    Benzocyclobutenones are an intriguing four-membered ring ketone. In the present thesis, we have developed a new protocol for selectively preparing benzocyclobutenones through intramolecular acylation of aryl bromides via palladium catalyzed C-H bond functionalization reactions based on rac-BINAP ligand. We also found that a subtle modification on the ligand backbone lead to a new catalytic manifold for preparing configurationally-pure styrene derivatives, when using dcpp (bis-dicyclohexylphos...

  2. Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency

    Andresen, B S; Olpin, S; Poorthuis, B J

    1999-01-01

    Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyop......Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence...... of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting......-phenotype relationship is in sharp contrast to what has been observed in medium-chain acyl-CoA dehydrogenase deficiency, in which no correlation between genotype and phenotype can be established....

  3. Acylated flavonol glycosides from Larix needles

    Niemann, Gerard J.

    2006-01-01

    Kaempferol-3-p-coumarylglucoside (KCG) was isolated from ether fractions of acetone-extracted freeze-dried needles of all larch species investigated. In each case, KCG was found as one of the main flavonoids, whereas often a variety of closely related, acylated flavonoids was present in either

  4. Veronica: Acylated flavone glycosides as chemosystematic markers

    Albach, Dirk C.; Grayer, Renée J.; Kite, Geoffrey C.

    2005-01-01

    HPLC/DAD and LCeMS of an extract of Veronica spicata subgenus Pseudolysimachium, Plantaginaceae) revealed the presence of six 6-hydroxyluteolin glycosides acylated with phenolic acids, three of which are new compounds and which we called spicosides. A flavonoid survey of seven more species...

  5. Internal catalysis in imine formation from acetone and acetone-d6 and conformationally constrained derivatives of N,N-dimethyl-1,3-propanediamine

    Hine, J.; Li, W.S.

    1975-01-01

    The kinetics of the reactions of 3-exo-dimethylaminomethyl-2-endo-norbornanamine (1), cis-2-(dimethylaminomethyl)cyclohexylamine (2), and 3-endo-dimethylaminomethyl-2-endo-norbornanamine (3) with acetone, and of these three diamines, neopentylamine, and 2-endo-norbornanamine with acetone-d 6 to give imines were studied at 35 0 and various pH's by use of hydroxylamine to capture the imines as they are formed. Acetone-d 6 was more reactive than acetone in the reactions with hydroxylamine alone as well as in the reactions with each of the diamines; the average k/sup D//k/sup H/ was 1.2. The rate constants for the monoprotonated diamines were so large relative to those for the unprotonated diamines that reliable values for the latter could not be obtained. The dominant reaction mechanism appears to be a reversible formation of the carbinolamine derived from the tertiary-protonated form of the monoprotonated diamine followed by rate-controlling internal acid-catalyzed formation of the iminium ion. The rate constants are compared with those obtained as a by-product of deuterium exchange studies of reactions of 1, 2, 3, and five other monoprotonated diamines by the same mechanism. The comparisons show that structural features that destabilize conformations in which the two amino groups are far apart may decrease the reactivity by relative stabilization []of a cyclic hydrogen-bonded form of the monoprotonated diamine as well as increasing the reactivity by relative stabilization of the transition state. Freezing the H 2 N--C--C--CH 2 NMe 2 dihedral angle of 1,3-diamines at values near 0, 60, and 120 0 does not give large differences in reactivity. Comparison of the rate constants for reactions of unprotonated neopentylamine and 2-endo-norbornanamine with those obtained previously for amines of the type XCH 2 CH 2 NH 2 gives no evidence for steric hindrance. (auth)

  6. Thermally Induced Denitrogenative Annulation for the Synthesis of Dihydroquinolinimines and Chroman-4-imines.

    Chou, Chih-Hung; Chen, Ying-Yu; Rajagopal, Basker; Tu, Hsiu-Chung; Chen, Kuan-Lin; Wang, Sheng-Fu; Liang, Chien-Fu; Tyan, Yu-Chang; Lin, Po-Chiao

    2016-03-04

    A rapid growth in synthetic methods for the preparation of diverse organic molecules using N-sulfonyl-1,2,3-triazoles is of great interest in organic synthesis. Transition metals are generally used to activate the α-imino diazo intermediates. Metal-free methods have not been studied in detail, but can be a good complement to transition metal catalysis in the mild reaction conditions. We herein report a novel method for the preparation of 2,3-dihydroquinolin-4-imine and chroman-4-imine analogs from their corresponding N-sulfonyl-1,2,3-triazoles in the absence of metal catalysts. To achieve intramolecular annulation, the introduction of an electron-donating group is required at the meta position of N-sulfonyl-1,2,3-triazole methyl anilines. The inclusion of tailored substituents on the aniline moieties and nitrogen atoms enhances the nucleophilicity of the phenyl π-electrons, thus allowing them to undergo a Friedel-Crafts-type reaction with the highly electrophilic ketenimines. This metal-free method was carefully optimized to generate a variety of dihydroquinolin-4-imines and chroman-4-imines in moderate-to-good yields. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Asymmetric aza-Diels-Alder reaction of Danishefsky's diene with imines in a chiral reaction medium

    Pégot Bruce

    2006-09-01

    Full Text Available Abstract The asymmetric aza-Diels-Alder reaction of chiral imines with Danishefsky's diene in chiral ionic liquids provides the corresponding cycloadduct with moderate to high diastereoselectivity. The reaction has proved to perform better at room temperature in ionic liquids without either Lewis acid catalyst or organic solvent. Chiral ionic liquids are recycled while their efficiency is preserved.

  8. An entry to a chiral dihydropyrazole scaffold: enantioselective [3 + 2] cycloaddition of nitrile imines.

    Sibi, Mukund P; Stanley, Levi M; Jasperse, Craig P

    2005-06-15

    We have developed a versatile strategy to access dihydropyrazoles in highly enantioenriched form. Dipolar cycloaddition of electron-deficient acceptors and in situ-generated nitrile imines proceeds with high regio- and enantioselectivity using 10 mol % chiral Lewis acid catalyst. A variety of dihydropyrazoles that incorporate functionality for further manipulation have been prepared.

  9. Functionalized Poly(propylene imine) Dendrimers as Novel Phase Transfer Catalyst in Supercritical Cabon Dioxide

    Goetheer, E.L.V.; Baars, M.W.P.L.; Broeke, van den L.J.P.; Meijer, E.W.; Keurentjes, J.T.F.

    2000-01-01

    Perfluoro-functionalized poly(propylene imine) dendrimers have been used as reactive extractants for anionic species and as phase transfer catalysts for two types of reactions. Different generations of dendrimers have been used for applications in carbon dioxide. First, the reactive extraction of

  10. Rhodium Catalyzed Decarbonylation

    Garcia Suárez, Eduardo José; Kahr, Klara; Riisager, Anders

    2017-01-01

    Rhodium catalyzed decarbonylation has developed significantly over the last 50 years and resulted in a wide range of reported catalyst systems and reaction protocols. Besides experimental data, literature also includes mechanistic studies incorporating Hammett methods, analysis of kinetic isotope...

  11. A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H-furanones

    Jubi John

    2014-06-01

    Full Text Available A facile route towards highly functionalized 3(2H-furanones via a sequential Mannich addition–palladium catalyzed ring closing has been elaborated. The reaction of 4-chloroacetoacetate esters with imines derived from aliphatic and aromatic aldehydes under palladium catalysis afforded 4-substituted furanones in good to excellent yields. 4-Hydrazino-3(2H-furanones could also be synthesized from diazo esters in excellent yields by utilising the developed strategy. We could also efficiently transform the substituted furanones to aza-prostaglandin analogues.

  12. Fatty Acyl Chains of Mycobacterium marinum Lipooligosaccharides

    Rombouts, Yoann; Alibaud, Laeticia; Carrère-Kremer, Séverine; Maes, Emmanuel; Tokarski, Caroline; Elass, Elisabeth; Kremer, Laurent; Guérardel, Yann

    2011-01-01

    We have recently established the fine structure of the glycan backbone of lipooligosaccharides (LOS-I to LOS-IV) isolated from Mycobacterium marinum, a close relative of Mycobacterium tuberculosis. These studies culminated with the description of an unusual terminal N-acylated monosaccharide that confers important biological functions to LOS-IV, such as macrophage activation, that may be relevant to granuloma formation. It was, however, also suggested that the lipid moiety was required for LOSs to exert their immunomodulatory activity. Herein, using highly purified LOSs from M. marinum, we have determined through a combination of mass spectrometric and NMR techniques, the structure and localization of the fatty acids composing the lipid moiety. The occurrence of two distinct polymethyl-branched fatty acids presenting specific localizations is consistent with the presence of two highly related polyketide synthases (Pks5 and Pks5.1) in M. marinum and presumably involved in the synthesis of these fatty acyl chains. In addition, a bioinformatic search permitted us to identify a set of enzymes potentially involved in the biosynthesis or transfer of these lipids to the LOS trehalose unit. These include MMAR_2343, a member of the Pap (polyketide-associated protein) family, that acylates trehalose-based glycolipids in M. marinum. The participation of MMAR_2343 to LOS assembly was demonstrated using a M. marinum mutant carrying a transposon insertion in the MMAR_2343 gene. Disruption of MMAR_2343 resulted in a severe LOS breakdown, indicating that MMAR_2343, hereafter designated PapA4, fulfills the requirements for LOS acylation and assembly. PMID:21803773

  13. Acylation Reactions over Zeolites and Mesoporous Catalysts

    Voláková, Martina; Vitvarová, Dana; Čejka, Jiří

    2009-01-01

    Roč. 2, č. 6 (2009), s. 486-499 ISSN 1864-5631 R&D Projects: GA ČR GA104/07/0383; GA ČR GD203/08/H032; GA MPO FT-TA5/005 Institutional research plan: CEZ:AV0Z40400503 Keywords : acylation * ketones * mesoporous materials * shape-selectivity * zeolites Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.767, year: 2009

  14. Profuse and Selective Growth in vitro of Rat Spinal Axons on a Micro-Patterned Poly (ethylene imine) Grid

    Mouveroux, J

    2001-01-01

    To distribute neurites (axons) along a surface and to guide them towards specific point targets we cultured spinal cord explants on coverslips printed with a micro-patterned grid of poly (ethylene imine) (PEI) lanes...

  15. Docking, synthesis and bioassay studies of imine derivatives as potential inhibitors for dengue NS2B/ NS3 serine protease

    Neni Frimayanti

    2017-11-01

    Full Text Available Objective: To search imine derivatives as new active agents against dengue type 2 NS2B/NS3 using molecular docking, since there is no effective vaccine against flaviviral infections. Methods: In this research, molecular docking was performed for a series of imine derivatives and the information obtained from the docking studies was used to explore the binding modes of these imine derivatives with dengue type 2 NS2B/NS3 serine protease. A set of imine were synthesized and bioassay study of the inhibitory activities of these compounds was then performed. Results: The results indicated that MY8 and MY4 have the ability to inhibit DEN2 NS2B/NS3 proteolytic activity. Conclusions: These two compounds were chosen as the reference for the next stage in drug design as new inhibitor agents against NS2B/NS3.

  16. An efficient protocol for the synthesis of highly sensitive indole imines utilizing green chemistry: optimization of reaction conditions.

    Nisar, Bushra; Rubab, Syeda Laila; Raza, Abdul Rauf; Tariq, Sobia; Sultan, Ayesha; Tahir, Muhammad Nawaz

    2018-04-11

    Novel and highly sensitive indole-based imines have been synthesized. Their synthesis has been compared employing a variety of protocols. Ultimately, a convenient, economical and high yielding set of conditions employing green chemistry have been designed for their synthesis.

  17. Purification, crystallization and preliminary crystallographic analysis of very-long-chain acyl-CoA dehydrogenase from Caenorhabditis elegans

    Li, Zhijie; Zhai, Yujia; Fang, Junnan; Zhou, Qiangjun; Geng, Yunqi; Sun, Fei

    2010-01-01

    Very-long-chain acyl-CoA dehydrogenase from Caenorhabditis elegans (cVLCAD) has been crystallized in space group C2 and its X-ray diffraction data set has been collected to 1.6 Å resolution. Unlike other VLCADs that were reported to form dimers, the purified cVLCAD was found as a homotetrameric protein according to static light-scattering measurements. Acyl-CoA dehydrogenase [acyl-CoA:(acceptor) 2,3-oxidoreductase; EC 1.3.99.3] catalyzes the first reaction step in mitochondrial fatty-acid β-oxidation. Here, the very-long-chain acyl-CoA dehydrogenase from Caenorhabditis elegans (cVLCAD) has been cloned and overexpressed in Escherichia coli strain BL21 (DE3). Interestingly, unlike other very-long-chain acyl-CoA dehydrogenases, cVLCAD was found to form a tetramer by size-exclusion chromatography coupled with in-line static light-scattering, refractive-index and ultraviolet measurements. Purified cVLCAD (12 mg ml −1 ) was successfully crystallized by the hanging-drop vapour-diffusion method under conditions containing 100 mM Tris–HCl pH 8.0, 150 mM sodium chloride, 200 mM magnesium formate and 13% PEG 3350. The crystal has a tetragonal form and a complete diffraction data set was collected and processed to 1.8 Å resolution. The crystal belonged to space group C2, with unit-cell parameters a = 138.6, b = 116.7, c = 115.3 Å, α = γ = 90.0, β = 124.0°. A self-rotation function indicated the existence of one noncrystallographic twofold axis. A preliminary molecular-replacement solution further confirmed the presence of two molecules in one asymmetric unit, which yields a Matthews coefficient V M of 2.76 Å 3 Da −1 and a solvent content of 55%

  18. The C-Terminal O-S Acyl Shift Pathway under Acidic Condition to Propose Peptide-Thioesters

    Bo Mi Kim

    2016-11-01

    Full Text Available Peptide-thioester is a pivotal intermediate for peptide ligation and N-, C-terminal cyclization. In this study, desired pathway and the side products of two C-terminal handles, hydroxyethylthiol (HET and hydroxypropylthiol (HPT are described in different conditions as well as kinetic studies. In addition, a new mechanism of C-terminal residue racemization is proposed on the basis of differentiation of products derived from the two C-terminal handles in preparing peptide thioesters through an acid-catalyzed tandem thiol switch, first by an intramolecular O-S acyl shift, and then by an intermolecular S-S exchange.

  19. Analytische und Effektor-Studien von N-Acyl-Ethanolaminphosphaten

    Ates, Ebru

    2011-01-01

    Bei N-Acyl-Ethanolaminphosphaten handelt es sich um eine bislang wenig untersuchte Klasse polarer Substanzen, deren Erforschung aufgrund ihrer strukturellen Analogie zu apolaren, physiologisch wirksamen N-Acyl-Ethanolaminen von Interesse ist. Zu bear-beiten waren analytische Fragestellungen, die auch synthetische Aufgaben beinhalteten, wie Methodenentwicklung und Versuche zur Erfassung von N-Acyl-Ethanolamin-phosphaten in ausgewählten Lebensmitteln sowie strukturelle Studien zur „Bioaktivität...

  20. N-Aryl-oxazolidin-2-imine Muscle Selective Androgen Receptor Modulators Enhance Potency through Pharmacophore Reorientation

    Nirschl, Alexandra A.; Zou, Yan; Krystek, Jr., Stanley R.; Sutton, James C.; Simpkins, Ligaya M.; Lupisella, John A.; Kuhns, Joyce E.; Seethala, Ramakrishna; Golla, Rajasree; Sleph, Paul G.; Beehler, Blake C.; Grover, Gary J.; Egan, Donald; Fura, Aberra; Vyas, Viral P.; Li, Yi-Xin; Sack, John S.; Kish, Kevin F.; An, Yongmi; Bryson, James A.; Gougoutas, Jack Z.; DiMarco, John; Zahler, Robert; Ostrowski, Jacek; Hamann, Lawrence G.; (BMS)

    2010-11-09

    A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model.

  1. Plasma levels of acylated ghrelin in patients with functional dyspepsia

    Kim, Yeon Soo; Lee, Joon Seong; Lee, Tae Hee; Cho, Joo Young; Kim, Jin Oh; Kim, Wan Jung; Kim, Hyun Gun; Jeon, Seong Ran; Jeong, Hoe Su

    2012-01-01

    AIM: To investigate the relationship between plasma acylated ghrelin levels and the pathophysiology of functional dyspepsia. METHODS: Twenty-two female patients with functional dyspepsia and twelve healthy volunteers were recruited for the study. The functional dyspepsia patients were each diagnosed based on the Rome III criteria. Eligible patients completed a questionnaire concerning the severity of 10 symptoms. Plasma acylated ghrelin levels before and after a meal were determined in the study participants using a commercial human acylated enzyme immunoassay kit; electrogastrograms were performed for 50 min before and after a standardized 10-min meal containing 265 kcal. RESULTS: There were no significant differences in plasma acylated ghrelin levels between healthy volunteers and patients with functional dyspepsia. However, in patients with functional dyspepsia, there was a negative correlation between fasting plasma acylated ghrelin levels and the sum score of epigastric pain (r = -0.427, P = 0.047) and a positive correlation between the postprandial/fasting plasma acylated ghrelin ratio and the sum score of early satiety (r = 0.428, P =0.047). Additionally, there was a negative correlation between fasting acylated ghrelin plasma levels and fasting normogastria (%) (r = -0.522, P = 0.013). Interestingly, two functional dyspepsia patients showed paradoxically elevated plasma acylated ghrelin levels after the meal. CONCLUSION: Abnormal plasma acylated ghrelin levels before or after a meal may be related to several of the dyspeptic symptoms seen in patients with functional dyspepsia. PMID:22611317

  2. Enantioselective [3+3] atroposelective annulation catalyzed by N-heterocyclic carbenes

    Zhao, Changgui

    2018-02-05

    Axially chiral molecules are among the most valuable substrates in organic synthesis. They are typically used as chiral ligands or catalysts in asymmetric reactions. Recent progress for the construction of these chiral molecules is mainly focused on the transition-metal-catalyzed transformations. Here, we report the enantioselective NHC-catalyzed (NHC: N-heterocyclic carbenes) atroposelective annulation of cyclic 1,3-diones with ynals. In the presence of NHC precatalyst, base, Lewis acid and oxidant, a catalytic C–C bond formation occurs, providing axially chiral α-pyrone−aryls in moderate to good yields and with high enantioselectivities. Control experiments indicated that alkynyl acyl azoliums, acting as active intermediates, are employed to atroposelectively assemble chiral biaryls and such a methodology may be creatively applied to other useful NHC-catalyzed asymmetric transformations.

  3. Electron induced conformational changes of an imine-based molecular switch on a Au(111) surface

    Lotze, Christian; Henningsen, Nils; Franke, Katharina; Schulze, Gunnar; Pascual, Jose Ignacio [Inst. f. Experimentalphysik, Freie Universitaet Berlin (Germany); Luo, Ying; Haag, Rainer [Inst. f. Organische Chemie, Freie Universitaet Berlin (Germany)

    2009-07-01

    Azobenzene-based molecules exhibit a cis-trans configurational photoisomerisation in solution. Recently, the adsorption properties of azobenzene derivatives have been investigated on different metal surfaces in order to explore the possible changes in the film properties induced by external stimuli. In azobenzene, the diazo-bridge is a key group for the isomerization process. Its interaction with a metal surface is dominated through the N lone-pair electrons, which reduces the efficiency of the conformational change. In order to reduce the molecule-surface interaction, we explore an alternative molecular architecture by substituting the diazo-bridge (-N=N-) of azobenzene by an imine-group (-N=CH-). We have investigated the imine-based compound para-carboxyl-di-benzene-imine (PCI) adsorbed on a Au(111) surface. The carboxylic terminations mediates the formation of strongly bonded molecular dimers, which align in ordered rows preferentially following the fcc regions of the Au(111) herringbone reconstruction. Low temperature scanning tunneling microscopy was used to induce conformational changes between trans and cis state of individual molecules in a molecular monolayer.

  4. EVALUATION OF ANTIOXIDANT ACTIVITY OF SOME IMINES DERIVATIVES OF L-ARGININE.

    Iacob, Andreea-Teodora; Drăgan, Maria; Constantin, Sandra; Lupaşcu, Florentina; Confederat, Luminiţa; Buron, F; Routier, S; Profire, Lenuţa

    2016-01-01

    L-Arginine is an a-amino acid which plays important roles in different diseases or processes, such as Alzheimer disease, inflammatory process, healing and tissue regeneration and it also could be useful as an anti-atherosclerotic agent. Considering the large amount of studies on the beneficial effects of different antioxidants, this paper is focused on the evaluation of the antioxidant potential of some imine derivatives, synthesized by the authors and described in a previous article. The evaluation of the antioxidant power was performed using phosphomolydenum-reducing antioxidant power (PRAP) and ferric reducing antioxidant power (FRAP) assays, tests described in the literature and which are used with some minor modifications. It was found that most of the imine derivatives are more active than the L-Arginine in the PPAP and FRAP assays. The most active derivative was the compound obtained by condensation of L-arginine with 2,3-dihydroxybenzaldehyde (2k) and 2-nitrobenzaldehyde (2g). Following the described protocol, some imine derivatives of L-arginine were evaluated in terms of antioxidant potential using in vitro methods. The most favorable influence was obtained by the aromatic substitution with nitro and hydroxyl, the corresponding derivatives being the most active derivatives compared to L-arginine.

  5. Electronic structure and UV spectra of N-arylthio-1,4-benzoquinone imines

    Pirozhenko, V.V.; Boldeskul, I.E.; Kolesnikov, V.T.; Vid, L.V.; Kuz'menko, L.O.

    1986-01-01

    The electronic structure of N-arylthio-1,4-benzoquinone imines (II) was studied by quantum-chemical methods (CNDO/2). It was shown that the special characteristics of the reactivity of the compounds in reaction with chlorine compared with sulfenylketimines R 2 C=N-S-Ar not containing a quinonoid ring may be due to the different nature of the lowest unoccupied molecular orbitals (LUMO). The UV spectra of compounds (II) were investigated. In the visible region the spectra of all the compounds contain strong absorption (R 1 = R 2 = R 3 = R 4 = R 5 = H, λ/sub m/ = 433 nm, epsilon/sub m/ = 2.12 x 10 4 liters/mole x cm), due to intramolecular charge transfer from the sulfur atom to the quinonoid fragment of the molecule. It was established that there is a linear relation between the energy of the transition and the σ + constants of the substituents in the aryl fragment. The assignment of the transitions was confirmed by calculations of the UV spectra of N-arylthio-1,4-benzoquinone imines by the PPP method. Comparison of the UV spectra of these compounds with the UV spectra of N-arylsulfonyl-1,4-benzoquinone imines makes it possible to conclude that the sulfur atom of the SO 2 group, unlike the divalent sulfur atom, is not capable of transmitting the electronic effects of the substituents from one part of the molecule to the other

  6. Electric-field triggered controlled release of bioactive volatiles from imine-based liquid crystalline phases.

    Herrmann, Andreas; Giuseppone, Nicolas; Lehn, Jean-Marie

    2009-01-01

    Application of an electric field to liquid crystalline film forming imines with negative dielectric anisotropy, such as N-(4-methoxybenzylidene)-4-butylaniline (MBBA, 1), results in the expulsion of compounds that do not participate in the formation of the liquid crystalline phase. Furthermore, amines and aromatic aldehydes undergo component exchange with the imine by generating constitutional dynamic libraries. The strength of the electric field and the duration of its application to the liquid crystalline film influence the release rate of the expelled compounds and, at the same time, modulate the equilibration of the dynamic libraries. The controlled release of volatile organic molecules with different chemical functionalities from the film was quantified by dynamic headspace analysis. In all cases, higher headspace concentrations were detected in the presence of an electric field. These results point to the possibility of using imine-based liquid crystalline films to build devices for the controlled release of a broad variety of bioactive volatiles as a direct response to an external electric signal.

  7. Improved Acylation of Phytosterols Catalyzed by Candida Antarctica Lipase a with Superior Catalytic Activity

    Panpipat, Worawan; Xu, Xuebing; Guo, Zheng

    Technical processes of chemical esterification presently used for the preparation of steryl esters are generally performed at high temperature in the presence of chemical catalyst, accompanying with high energy consumption, browning of products and low selectivity. This work reported a novel appr...

  8. Improved acylation of phytosterols catalyzed by Candida antarctica lipase A with superior catalytic activity

    Panpipat, Worawan; Xu, Xuebing; Guo, Zheng

    2013-01-01

    with structural identification of products by 1H NMR and Fourier transform-infrared spectroscopy (FTIR). Compared to other immobilized lipases, CAL A achieves 6–14 times faster esterification of ˇ-sitosterol with myristic acid. CAL A shows low activity toward short chain fatty acids (C2–C6), and remarkably high...... activity for medium and long chain ones (≥C8). Reaction time, temperature, enzyme load, substrate ratio and concentration, and solvent property are found to profoundly influence reaction rates. A pronounced correlation between enzyme activities and log P values of solvents, among the solvents with a broad...... spectrum of log P values, was observed. 93–98% yield of ˇ-sitosteryl esters could be achieved with hexane as solvent, fatty acid (C8–C18)/ˇ-sitosterol (1:1, mol:mol), 5–10% CAL A load at 40–50 ◦C for 24 h. This work demonstrated the promising potential of CAL A in bioprocess of phytosterols for value...

  9. Localization of acyl ghrelin- and des-acyl ghrelin-immunoreactive cells in the rat stomach and their responses to intragastric pH.

    Mizutani, Makoto; Atsuchi, Kaori; Asakawa, Akihiro; Matsuda, Norifumi; Fujimura, Masaki; Inui, Akio; Kato, Ikuo; Fujimiya, Mineko

    2009-11-01

    Acyl ghrelin has a 28-amino acid sequence with O-n-octanoyl acid modification at the serine 3 position, whereas des-acyl ghrelin has no octanoyl acid modification. Although these peptides exert different physiological functions, no previous studies have shown the different localization of acyl ghrelin and des-acyl ghrelin in the stomach. Here we have developed an antibody specific for des-acyl ghrelin that does not crossreact with acyl ghrelin. Both acyl ghrelin- and des-acyl ghrelin-immunoreactive cells were distributed in the oxyntic and antral mucosa of the rat stomach, with higher density in the antral mucosa than oxyntic mucosa. Immunofluorescence double staining showed that acyl ghrelin- and des-acyl ghrelin-positive reactions overlapped in closed-type round cells, whereas des-acyl ghrelin-positive reaction was found in open-type cells in which acyl ghrelin was negative. Acyl ghrelin-/des-acyl ghrelin-positive closed-type cells contain obestatin; on the other hand, des-acyl ghrelin-positive open-type cells contain somatostatin. We measured the release of acyl ghrelin and des-acyl ghrelin in vascularly perfused rat stomach by ELISA, and the effects of different intragastric pH levels on the release of each peptide were examined. The release of des-acyl ghrelin from the perfused stomach was greater at pH 2 than at pH 4; however, the release of acyl ghrelin was not affected by intragastric pH. The present study demonstrated the differential localization of acyl ghrelin and des-acyl ghrelin in the rat stomach and their different responses to the intragastric pH.

  10. Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein

    Ferreira, Natalia Santos; Engelsby, Hanne; Neess, Ditte

    2017-01-01

    and cardiovascular diseases, as well as neurological disorders. Here we show that acyl-coenzyme A-binding protein (ACBP) potently facilitates very-long acyl chain ceramide synthesis. ACBP increases the activity of ceramide synthase 2 (CerS2) by more than 2-fold and CerS3 activity by 7-fold. ACBP binds very......-long-chain acyl-CoA esters, which is required for its ability to stimulate CerS activity. We also show that high-speed liver cytosol from wild-type mice activates CerS3 activity, whereas cytosol from ACBP knock-out mice does not. Consistently, CerS2 and CerS3 activities are significantly reduced in the testes...... of ACBP(-/-) mice, concomitant with a significant reduction in long- and very-long-chain ceramide levels. Importantly, we show that ACBP interacts with CerS2 and CerS3. Our data uncover a novel mode of regulation of very-long acyl chain ceramide synthesis by ACBP, which we anticipate is of crucial...

  11. LOCATION OF ACYL GROUPS ON TWO PARTLY ACYLATED GLYCOLIPIDS FROM STRAINS OF USTILAGO (SMUT FUNGI),

    erythritol from Ustilago sp. (probably U. nuda (Jens.) Rostr. = U. tritici (Pers.) Rostr.) PRL-627 were acetalated with methyl vinyl ether, deacylated...Partly acylated ustilagic acids 8 (from Ustilago maydis (DC) Corda (= U. zeae Unger) PRL-119), consisting of partially esterified beta-cellobiosyl

  12. Reprogramming Acyl Carrier Protein Interactions of an Acyl-CoA Promiscuous trans-Acyltransferase

    Ye, Zhixia; Musiol-Kroll, Ewa Maria; Weber, Tilmann

    2014-01-01

    Protein interactions between acyl carrier proteins (ACPs) and trans-acting acyltransferase domains (trans-ATs) are critical for regioselective extender unit installation by many polyketide synthases, yet little is known regarding the specificity of these interactions, particularly for trans-ATs w...

  13. An Efficient, Mild and Solvent-Free Synthesis of Benzene Ring Acylated Harmalines

    Sabira Begum

    2009-12-01

    Full Text Available A facile synthesis of a series of benzene ring acylated analogues of harmaline has been achieved by Friedel-Crafts acylation under solvent-free conditions at room temperature using acyl halides/acid anhydrides and AlCl3. The reaction afforded 10- and 12-acyl analogues of harmaline in good yield, along with minor quantities of N-acyl-tryptamines and 8-acyl analogues of N-acyltryptamines.

  14. Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate

    Yoshimi eMatsumoto

    2012-02-01

    Full Text Available (--Epigallocatechin-3-O-gallate (EGCG has useful antiviral, antimicrobial, antitoxin, and antitumor properties. Previously, Mori, S. et al. (Bioorg Med Chem Lett 18:4249-4252, 2008 found that addition of long acyl chains (C16–18 to EGCG enhanced its anti-influenza virus activity up to 44-fold. The chemical stability of EGCG against oxidative degradation was also enhanced by acylation. We further evaluated the in vitro activity spectrum of the EGCG derivatives against a wide range of bacteria and fungi. A series of EGCG O-acyl derivatives were synthesized by lipase-catalyzed transesterification. These derivatives exhibited several-fold higher activities than EGCG, particularly against Gram-positive organisms. Antifungal activities of the derivatives were also 2 to 4-fold superior to those of EGCG. The activities of the EGCG derivatives against Gram-negative bacteria were not distinguishable from those of EGCG. Among the derivatives evaluated, MICs of dioctanoate, palmitate (C16, palmitoleate, and linolenate for 17 Staphylococcus aureus strains were 4–32 μg/ml, although MIC of EGCG for these 17 strains was >128 μg/ml. C16 demonstrated rapid bactericidal activity against MRSA at 25 μg/ml. The enhanced activity of C16 against S. aureus was supported by its increased membrane permeabilizing activity determined by increased SYTOX Green uptake. The EGCG derivatives were exported by the efflux pump AcrAB-TolC of Escherichia coli. The tolC deletion mutant exhibited higher sensitivity to C16 than to EGCG. Addition of long alkyl chains to EGCG significantly enhanced its activities against various bacteria and fungi, particularly against S. aureus including MRSA. C16 would be an alternative to antibiotics and disinfectants.

  15. Only Acyl Carrier Protein 1 (AcpP1 Functions in Pseudomonas aeruginosa Fatty Acid Synthesis

    Jin-Cheng Ma

    2017-11-01

    Full Text Available The genome of Pseudomonas aeruginosa contains three open reading frames, PA2966, PA1869, and PA3334, which encode putative acyl carrier proteins, AcpP1, AcpP2, and AcpP3, respectively. In this study, we found that, although these apo-ACPs were successfully phosphopantetheinylated by P. aeruginosa phosphopantetheinyl transferase (PcpS and all holo-forms of these proteins could be acylated by Vibrio harveyi acyl-ACP synthetase (AasS, only AcpP1 could be used as a substrate for the synthesis of fatty acids, catalyzed by P. aeruginosa cell free extracts in vitro, and only acpP1 gene could restore growth in the Escherichia coliacpP mutant strain CY1877. And P. aeruginosaacpP1 could not be deleted, while disruption of acpP2 or acpP3 in the P. aeruginosa genome allowed mutant strains to grow as well as the wild type strain. These findings confirmed that only P. aeruginosa AcpP1 functions in fatty acid biosynthesis, and that acpP2 and acpP3 do not play roles in the fatty acid synthetic pathway. Moreover, disruption of acpP2 and acpP3 did not affect the ability of P. aeruginosa to produce N-acylhomoserine lactones (AHL, but replacement of P. aeruginosaacpP1 with E. coliacpP caused P. aeruginosa to reduce the production of AHL molecules, which indicated that neither P. aeruginosa AcpP2 nor AcpP3 can act as a substrate for synthesis of AHL molecules in vivo. Furthermore, replacement of acpP1 with E. coliacpP reduced the ability of P. aeruginosa to produce some exo-products and abolished swarming motility in P. aeruginosa.

  16. Ultrasonic pretreatment for lipase-catalyed synthesis of phytosterol esters with different acyl donors.

    Zheng, Ming-Ming; Wang, Lian; Huang, Feng-Hong; Dong, Ling; Guo, Ping-Mei; Deng, Qian-Chun; Li, Wen-Lin; Zheng, Chang

    2012-09-01

    This study is focused on the enzymatic esterification of phytosterols with different acyl donors to produce the corresponding phytosterol esters catalyzed by Canadia sp. 99-125 lipase under ultrasound irradiation. An ultrasonic frequency of 35 kHz, power of 200 W and time of 1h was determined to guarantee satisfactory degree of esterification and lipase activity. The influence of temperature, substrates concentration and molar ratio was investigated subsequently. The optimum production was achieved in isooctane system at 60°C with phytosterol concentration of 150 μmol/mL and phytosterol to fatty acid molar ratio of 1:1.5, resulting in a phytosterol esters conversion of above 85.7% in short reaction time (8h). Phytosterols esters could also be converted in high yields to the corresponding long-chain acyl esters via transesterification with triacylglycerols (above 90.3%) under ultrasound irradiation. In optimum conditions, the overall esterification reaction rate using the ultrasonic pretreatment process was above 2-fold than that of mechanical stirring process without damage the lipase activity. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Lipases in green chemistry: acylation and alcoholysis on steroids and nucleosides.

    Baldessari, Alicia; Iglesias, Luis E

    2012-01-01

    In this article, we describe the application of lipases in acylation and alcoholysis reactions on steroids and nucleosides. In the field of steroids, a variety of acetyl and fatty acid derivatives of androstanes, pregnanes, and cholestanes have been prepared through lipase-catalyzed acylation and alcoholysis reactions taking advantage of the high regio- and stereoselectivity of these enzymes. The substrates as well as the products show a high degree of biological activity as neurosteroids, hormones, and glucocorticoids. The regioselective preparation of diacylated nucleosides by means of an enzymatic alcoholysis allowed the synthesis of nucleosides prodrugs or modified nucleosides. The quantitative full deacylation and dealkoxycarbonylation of nucleosides and steroids is a mild synthetic method for the deprotection of these labile compounds. Some of the reported steroid and nucleoside products are novel, and it is not possible to obtain them satisfactorily by following traditional synthetic procedures. The advantages presented by this methodology, such as selectivity, mild reaction conditions, and low environmental impact, make the lipases an important tool in the application of the principles of Green Chemistry, offering a convenient way to prepare derivatives of natural compounds with a great potential in the pharmaceutical industry.

  18. A Convenient Synthesis of Conjugated Acetylenic Ketones by Copper(l)-Catalyzed under Microwave Irradiation

    WANG; JinXian

    2001-01-01

    Alkynyl ketones are useful precursors and intermediates in synthetic organic chemistry1 and has evoked considerable interest. A number of methods for the synthesis of conjugated acetylenic ketones involve the reaction a metal acetylide with an acyl chlorides or another carboxylic acid derivative have been developed 2. Recently, the synthesis of α, β-conjugated acetylenic ketones catalyzed by Pd(Ⅱ) or by copper(Ⅰ)pd(Ⅱ) reaction of 1-alkynes and acyl chlorides have been described. The acylation of terminal alkynes by acyl chlorides in the presence of catalytic amounts copper(Ⅰ) salts leading to α, β-conjugated acetylenic ketones has also been reported. However, many of these reactions suffer from lack of high pressure (17 atm), long reaction time (30 h)and require low temperatures (-78℃). Our work involves the synthesis of conjugated acetylenic ketones via the reaction of terminal alkynes with aroyl chlorides in the presence of cuprous iodide under microwave irradiation conditions.……

  19. Enantioselective resolution of (R,S)-1-phenylethanol catalyzed by lipases immobilized in starch films

    Hoffmann, Isabel; Silva, Vanessa D.; Nascimento, Maria da G.

    2011-01-01

    Lipases from different sources and two mycelium-bound lipases, in a free or immobilized form, in ginger starch film were screened as biocatalysts in the reaction of (R,S)-1-phenylethanol (1) with vinyl acetate and other acylating agents. The effect of various reaction parameters in the resolution of (1) catalyzed by lipase from Burkholderia cepacia (BCL) immobilized in ginger starch film was evaluated (acyl donor type, alcohol:acyl donor molar ratio, temperature and organic solvent). The catalytic efficiency of BCL immobilized in polymeric blends of ginger starch and polyethylene oxide (PEO), in different compositions, was also studied. Vinyl acetate and iso-propenyl acetate furnished the highest conversion (9%) and enantiomeric excess (> 99%) of the (R)-ester. The alcohol:acyl donor molar ratio and temperature optimum were 1:1 and 28 deg respectively. The mixture of n-hexane/glycerol (9:1 v:v) was the most adequate for this reaction (conversion 23%, E > 200). The ginger starch/PEO (7:3 m/m) blend was successfully reused six times consecutively. (author)

  20. Enantioselective resolution of (R,S)-1-phenylethanol catalyzed by lipases immobilized in starch films

    Hoffmann, Isabel; Silva, Vanessa D.; Nascimento, Maria da G., E-mail: graca@qmc.ufsc.b [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Dept. de Quimica

    2011-07-01

    Lipases from different sources and two mycelium-bound lipases, in a free or immobilized form, in ginger starch film were screened as biocatalysts in the reaction of (R,S)-1-phenylethanol (1) with vinyl acetate and other acylating agents. The effect of various reaction parameters in the resolution of (1) catalyzed by lipase from Burkholderia cepacia (BCL) immobilized in ginger starch film was evaluated (acyl donor type, alcohol:acyl donor molar ratio, temperature and organic solvent). The catalytic efficiency of BCL immobilized in polymeric blends of ginger starch and polyethylene oxide (PEO), in different compositions, was also studied. Vinyl acetate and iso-propenyl acetate furnished the highest conversion (9%) and enantiomeric excess (> 99%) of the (R)-ester. The alcohol:acyl donor molar ratio and temperature optimum were 1:1 and 28 deg respectively. The mixture of n-hexane/glycerol (9:1 v:v) was the most adequate for this reaction (conversion 23%, E > 200). The ginger starch/PEO (7:3 m/m) blend was successfully reused six times consecutively. (author)

  1. Understanding Acyl Chain and Glycerolipid Metabolism in Plants

    Ohlrogge, John B.

    2013-11-05

    Progress is reported in these areas: acyl-editing in initial eukaryotic lipid assembly in soybean seeds; identification and characterization of two Arabidopsis thaliana lysophosphatidyl acyltransferases with preference for lysophosphatidylethanolamine; and characterization and subcellular distribution of lysolipid acyl transferase activity of pea leaves.

  2. Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin

    Asakawa, A; Inui, A; Fujimiya, M; Sakamaki, R; Shinfuku, N; Ueta, Y; Meguid, M M; Kasuga, M

    2005-01-01

    Background/Aims: The gastric peptide ghrelin, an endogenous ligand for growth-hormone secretagogue receptor, has two major molecular forms: acylated ghrelin and desacyl ghrelin. Acylated ghrelin induces a positive energy balance, while desacyl ghrelin has been reported to be devoid of any endocrine activities. The authors examined the effects of desacyl ghrelin on energy balance.

  3. Characterization of the "Escherichia Coli" Acyl Carrier Protein Phosphodiesterase

    Thomas, Jacob

    2009-01-01

    Acyl carrier protein (ACP) is a small essential protein that functions as a carrier of the acyl intermediates of fatty acid synthesis. ACP requires the posttranslational attachment of a 4'phosphopantetheine functional group, derived from CoA, in order to perform its metabolic function. A Mn[superscript 2+] dependent enzymatic activity that removes…

  4. Oxidative activation of dihydropyridine amides to reactive acyl donors

    Funder, Erik Daa; Trads, Julie Brender; Gothelf, Kurt Vesterager

    2015-01-01

    Amides of 1,4-dihydropyridine (DHP) are activated by oxidation for acyl transfer to amines, alcohols and thiols. In the reduced form the DHP amide is stable towards reaction with amines at room temperature. However, upon oxidation with DDQ the acyl donor is activated via a proposed pyridinium...

  5. Enoyl-Acyl Carrier Protein Reductase I (FabI) Is Essential for the Intracellular Growth of Listeria monocytogenes

    Ericson, Megan E.; Frank, Matthew W.

    2016-01-01

    Enoyl-acyl carrier protein reductase catalyzes the last step in each elongation cycle of type II bacterial fatty acid synthesis and is a key regulatory protein in bacterial fatty acid synthesis. Genes of the facultative intracellular pathogen Listeria monocytogenes encode two functional enoyl-acyl carrier protein isoforms based on their ability to complement the temperature-sensitive growth phenotype of Escherichia coli strain JP1111 [fabI(Ts)]. The FabI isoform was inactivated by the FabI selective inhibitor AFN-1252, but the FabK isoform was not affected by the drug, as expected. Inhibition of FabI by AFN-1252 decreased endogenous fatty acid synthesis by 80% and lowered the growth rate of L. monocytogenes in laboratory medium. Robust exogenous fatty acid incorporation was not detected in L. monocytogenes unless the pathway was partially inactivated by AFN-1252 treatment. However, supplementation with exogenous fatty acids did not restore normal growth in the presence of AFN-1252. FabI inactivation prevented the intracellular growth of L. monocytogenes, showing that neither FabK nor the incorporation of host cellular fatty acids was sufficient to support the intracellular growth of L. monocytogenes. Our results show that FabI is the primary enoyl-acyl carrier protein reductase of type II bacterial fatty acid synthesis and is essential for the intracellular growth of L. monocytogenes. PMID:27736774

  6. Radiochemical methods for studying lipase-catalyzed interesterification of lipids

    Schuch, R.; Mukherjee, K.D.

    1987-01-01

    Reactions involving lipase-catalyzed interesterification of lipids, which are of commendable interest in biotechnology, have been monitored and assayed by radiochemical methods using 14 C-labeled substrates. Medium chain (C 12 plus C 14 ) triacylglycerols were reacted in the presence of an immobilized lipase from Mucor miehei and hexane at 45 0 C with methyl [1- 14 C]oleate, [1- 14 C]oleic acid, [carboxyl- 14 C]trioleoylglycerol, [1- 14 C]octadecenyl alcohol, and [U- 14 C]glycerol, each of known specific activity. The reactions were monitored and the rate of interesterification determined by radio thin layer chromatography from the incorporation of radioactivity into acyl moieties of triacylglycerols (from methyl oleate, oleic acid, and trioleoylglycerol), alkyl moieties of wax esters (from octadecenyl alcohol), and into glycerol backbone of monoacylglycerols and diacylglycerols (from glycerol). (orig.)

  7. Caffeine-catalyzed gels.

    DiCiccio, Angela M; Lee, Young-Ah Lucy; Glettig, Dean L; Walton, Elizabeth S E; de la Serna, Eva L; Montgomery, Veronica A; Grant, Tyler M; Langer, Robert; Traverso, Giovanni

    2018-07-01

    Covalently cross-linked gels are utilized in a broad range of biomedical applications though their synthesis often compromises easy implementation. Cross-linking reactions commonly utilize catalysts or conditions that can damage biologics and sensitive compounds, producing materials that require extensive post processing to achieve acceptable biocompatibility. As an alternative, we report a batch synthesis platform to produce covalently cross-linked materials appropriate for direct biomedical application enabled by green chemistry and commonly available food grade ingredients. Using caffeine, a mild base, to catalyze anhydrous carboxylate ring-opening of diglycidyl-ether functionalized monomers with citric acid as a tri-functional crosslinking agent we introduce a novel poly(ester-ether) gel synthesis platform. We demonstrate that biocompatible Caffeine Catalyzed Gels (CCGs) exhibit dynamic physical, chemical, and mechanical properties, which can be tailored in shape, surface texture, solvent response, cargo release, shear and tensile strength, among other potential attributes. The demonstrated versatility, low cost and facile synthesis of these CCGs renders them appropriate for a broad range of customized engineering applications including drug delivery constructs, tissue engineering scaffolds, and medical devices. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in Caenorhabditis elegans

    Zhang, Xinxing; Jones, Rachel A.; Bruner, Steven D.; Butcher, Rebecca A.

    2016-01-01

    Caenorhabditis elegans secretes ascarosides as pheromones to communicate with other worms and to coordinate the development and behavior of the population. Peroxisomal β-oxidation cycles shorten the side chains of ascaroside precursors to produce the short-chain ascaroside pheromones. Acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, have different side chain-length specificities and enable C. elegans to regulate the production of specific ascaroside pheromones. Here, we determine the crystal structure of the acyl-CoA oxidase 1 (ACOX-1) homodimer and the ACOX-2 homodimer bound to its substrate. Our results provide a molecular basis for the substrate specificities of the acyl-CoA oxidases and reveal why some of these enzymes have a very broad substrate range, whereas others are quite specific. Our results also enable predictions to be made for the roles of uncharacterized acyl-CoA oxidases in C. elegans and in other nematode species. Remarkably, we show that most of the C. elegans acyl-CoA oxidases that participate in ascaroside biosynthesis contain a conserved ATP-binding pocket that lies at the dimer interface, and we identify key residues in this binding pocket. ATP binding induces a structural change that is associated with tighter binding of the FAD cofactor. Mutations that disrupt ATP binding reduce FAD binding and reduce enzyme activity. Thus, ATP may serve as a regulator of acyl-CoA oxidase activity, thereby directly linking ascaroside biosynthesis to ATP concentration and metabolic state. PMID:27551084

  9. Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in Caenorhabditis elegans.

    Zhang, Xinxing; Li, Kunhua; Jones, Rachel A; Bruner, Steven D; Butcher, Rebecca A

    2016-09-06

    Caenorhabditis elegans secretes ascarosides as pheromones to communicate with other worms and to coordinate the development and behavior of the population. Peroxisomal β-oxidation cycles shorten the side chains of ascaroside precursors to produce the short-chain ascaroside pheromones. Acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, have different side chain-length specificities and enable C. elegans to regulate the production of specific ascaroside pheromones. Here, we determine the crystal structure of the acyl-CoA oxidase 1 (ACOX-1) homodimer and the ACOX-2 homodimer bound to its substrate. Our results provide a molecular basis for the substrate specificities of the acyl-CoA oxidases and reveal why some of these enzymes have a very broad substrate range, whereas others are quite specific. Our results also enable predictions to be made for the roles of uncharacterized acyl-CoA oxidases in C. elegans and in other nematode species. Remarkably, we show that most of the C. elegans acyl-CoA oxidases that participate in ascaroside biosynthesis contain a conserved ATP-binding pocket that lies at the dimer interface, and we identify key residues in this binding pocket. ATP binding induces a structural change that is associated with tighter binding of the FAD cofactor. Mutations that disrupt ATP binding reduce FAD binding and reduce enzyme activity. Thus, ATP may serve as a regulator of acyl-CoA oxidase activity, thereby directly linking ascaroside biosynthesis to ATP concentration and metabolic state.

  10. Enzyme-Catalyzed Regioselective Modification of Starch Nanoparticles

    Chakraborty, Soma [Polytechnic Univ., Brooklyn, NY (United States). National Science Foundation (NSF) Center for Biocatalysis and Bioprocessing of Macromolecules, Othmer Dept. of Chemical and Biological Science and Engineering; Sahoo, Bishwabhusan [Polytechnic Univ., Brooklyn, NY (United States). National Science Foundation (NSF) Center for Biocatalysis and Bioprocessing of Macromolecules, Othmer Dept. of Chemical and Biological Science and Engineering; Teraoka, Iwao [Polytechnic Univ., Brooklyn, NY (United States). National Science Foundation (NSF) Center for Biocatalysis and Bioprocessing of Macromolecules, Othmer Dept. of Chemical and Biological Science and Engineering; Miller, Lisa M. [Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source (NSLS); Gross, Richard A. [Polytechnic Univ., Brooklyn, NY (United States). National Science Foundation (NSF) Center for Biocatalysis and Bioprocessing of Macromolecules, Othmer Dept. of Chemical and Biological Science and Engineering

    2004-12-13

    The selective esterification of starch nanoparticles was performed using as catalyst Candida antartica Lipase B (CAL-B) in its immobilized (Novozym 435) and free (SP-525) forms. The starch nanoparticles were made accessible for acylation reactions by formation of Aerosol-OT (AOT, bis(2-ethylhexyl)sodium sulfosuccinate) stabilized microemulsions. Starch nanoparticles in microemulsions were reacted with vinyl stearate, ε-caprolactone, and maleic anhydride at 40 °C for 48 h to give starch esters with degrees of substitution (DS) of 0.8, 0.6, and 0.4, respectively. Substitution occurred regioselectively at the C-6 position of the glucose repeat units. Infrared microspectroscopy (IRMS) revealed that AOT-coated starch nanoparticles diffuse into the outer 50 μm shell of catalyst beads. Thus, even though CAL-B is immobilized within a macroporous resin, CAL-B is sufficiently accessible to the starch nanoparticles. When free CAL-B was incorporated along with starch within AOT-coated reversed micelles, CAL-B was also active and catalyzed the acylation with vinyl stearate (24 h, 40 °C) to give DS = 0.5. After removal of surfactant from the modified starch nanoparticles, they were dispersed in DMSO or water and were shown to retain their nanodimensions.

  11. Asymmetric Synthesis of Hydrocarbazoles Catalyzed by an Octahedral Chiral-at-Rhodium Lewis Acid.

    Huang, Yong; Song, Liangliang; Gong, Lei; Meggers, Eric

    2015-12-01

    A bis-cyclometalated chiral-at-metal rhodium complex catalyzes the Diels-Alder reaction between N-Boc-protected 3-vinylindoles (Boc = tert-butyloxycarbonyl) and β-carboxylic ester-substituted α,β-unsaturated 2-acyl imidazoles with good-to-excellent regioselectivity (up to 99:1) and excellent diastereoselectivity (>50:1 d.r.) as well as enantioselectivity (92-99% ee) under optimized conditions. The rhodium catalyst serves as a chiral Lewis acid to activate the 2-acyl imidazole dienophile by two-point binding and overrules the preferred regioselectivity of the uncatalyzed reaction. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Hydrophosphination of alkynes and related reactions catalyzed by rare-earth amides

    Takaki, Ken; Komeyama, Kimihiro; Kobayashi, Daisuke; Kawabata, Tomonori; Takehira, Katsuomi

    2006-01-01

    Intermolecular hydrophosphination of alkynes with Ph 2 PH was effectively catalyzed by Yb-imine complex [Yb(η 2 -Ph 2 CNPh)(hmpa) 3 ], in which the empirical rate law was described as v = k [catalyst] 2 [alkyne] 1 [phosphine] . The active catalysts were proved to be ytterbium(II) mono- and diphosphido species generated in situ. Although trivalent phosphido complex [Yb(PPh 2 ) 3 (hmpa) n ], gave the same results as the divalent complexes, Yb metals of the both complexes seemed to keep their original oxidation state unchanged. When Ph 2 PH was substituted by Ph 2 P-SiMe 3 , silylphosphination of aromatic internal alkynes took place to afford 1-trimethylsilyl-2-diphenylphosphinoalkenes in moderate yields. Moreover, one-pot synthesis of 1-diphenylphosphino-1,3-butadienes from terminal alkynes and Ph 2 PH has been achieved using Y[N(SiMe 3 ) 2 ] 3 catalyst through the alkyne dimerization and subsequent hydrophosphination

  13. Merging constitutional and motional covalent dynamics in reversible imine formation and exchange processes.

    Kovaříček, Petr; Lehn, Jean-Marie

    2012-06-06

    The formation and exchange processes of imines of salicylaldehyde, pyridine-2-carboxaldehyde, and benzaldehyde have been studied, showing that the former has features of particular interest for dynamic covalent chemistry, displaying high efficiency and fast rates. The monoimines formed with aliphatic α,ω-diamines display an internal exchange process of self-transimination type, inducing a local motion of either "stepping-in-place" or "single-step" type by bond interchange, whose rate decreases rapidly with the distance of the terminal amino groups. Control of the speed of the process over a wide range may be achieved by substituents, solvent composition, and temperature. These monoimines also undergo intermolecular exchange, thus merging motional and constitutional covalent behavior within the same molecule. With polyamines, the monoimines formed execute internal motions that have been characterized by extensive one-dimensional, two-dimensional, and EXSY proton NMR studies. In particular, with linear polyamines, nondirectional displacement occurs by shifting of the aldehyde residue along the polyamine chain serving as molecular track. Imines thus behave as simple prototypes of systems displaying relative motions of molecular moieties, a subject of high current interest in the investigation of synthetic and biological molecular motors. The motional processes described are of dynamic covalent nature and take place without change in molecular constitution. They thus represent a category of dynamic covalent motions, resulting from reversible covalent bond formation and dissociation. They extend dynamic covalent chemistry into the area of molecular motions. A major further step will be to achieve control of directionality. The results reported here for imines open wide perspectives, together with other chemical groups, for the implementation of such features in multifunctional molecules toward the design of molecular devices presenting a complex combination of

  14. Structure, High Affinity, and Negative Cooperativity of the Escherichia coli Holo-(Acyl Carrier Protein):Holo-(Acyl Carrier Protein) Synthase Complex

    Marcella, Aaron M.; Culbertson, Sannie J.; Shogren-Knaak, Michael A.; Barb, Adam W.

    2017-11-01

    The Escherichia coli holo-(acyl carrier protein) synthase (ACPS) catalyzes the coenzyme A-dependent activation of apo-ACPP to generate holo-(acyl carrier protein) (holo-ACPP) in an early step of fatty acid biosynthesis. E. coli ACPS is sufficiently different from the human fatty acid synthase to justify the development of novel ACPS-targeting antibiotics. Models of E. coli ACPS in unliganded and holo-ACPP-bound forms solved by X-ray crystallography to 2.05 and 4.10 Å, respectively, revealed that ACPS bound three product holo-ACPP molecules to form a 3:3 hexamer. Solution NMR spectroscopy experiments validated the ACPS binding interface on holo-ACPP using chemical shift perturbations and by determining the relative orientation of holo-ACPP to ACPS by fitting residual dipolar couplings. The binding interface is organized to arrange contacts between positively charged ACPS residues and the holo-ACPP phosphopantetheine moiety, indicating product contains more stabilizing interactions than expected in the enzyme:substrate complex. Indeed, holo-ACPP bound the enzyme with greater affinity than the substrate, apo-ACPP, and with negative cooperativity. The first equivalent of holo-ACPP bound with a KD = 62 ± 13 nM, followed by the binding of two more equivalents of holo-ACPP with KD = 1.2 ± 0.2 μM. Cooperativity was not observed for apo-ACPP which bound with KD = 2.4 ± 0.1 μM. Strong product binding and high levels of holo-ACPP in the cell identify a potential regulatory role of ACPS in fatty acid biosynthesis.

  15. Structure, High Affinity, and Negative Cooperativity of the Escherichia coli Holo-(Acyl Carrier Protein):Holo-(Acyl Carrier Protein) Synthase Complex.

    Marcella, Aaron M; Culbertson, Sannie J; Shogren-Knaak, Michael A; Barb, Adam W

    2017-11-24

    The Escherichia coli holo-(acyl carrier protein) synthase (ACPS) catalyzes the coenzyme A-dependent activation of apo-ACPP to generate holo-(acyl carrier protein) (holo-ACPP) in an early step of fatty acid biosynthesis. E. coli ACPS is sufficiently different from the human fatty acid synthase to justify the development of novel ACPS-targeting antibiotics. Models of E. coli ACPS in unliganded and holo-ACPP-bound forms solved by X-ray crystallography to 2.05and 4.10Å, respectively, revealed that ACPS bound three product holo-ACPP molecules to form a 3:3 hexamer. Solution NMR spectroscopy experiments validated the ACPS binding interface on holo-ACPP using chemical shift perturbations and by determining the relative orientation of holo-ACPP to ACPS by fitting residual dipolar couplings. The binding interface is organized to arrange contacts between positively charged ACPS residues and the holo-ACPP phosphopantetheine moiety, indicating product contains more stabilizing interactions than expected in the enzyme:substrate complex. Indeed, holo-ACPP bound the enzyme with greater affinity than the substrate, apo-ACPP, and with negative cooperativity. The first equivalent of holo-ACPP bound with a K D =62±13nM, followed by the binding of two more equivalents of holo-ACPP with K D =1.2±0.2μM. Cooperativity was not observed for apo-ACPP which bound with K D =2.4±0.1μM. Strong product binding and high levels of holo-ACPP in the cell identify a potential regulatory role of ACPS in fatty acid biosynthesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Catalyzing alignment processes

    Lauridsen, Erik Hagelskjær; Jørgensen, Ulrik

    2004-01-01

    This paper describes how environmental management systems (EMS) spur the circulation of processes that support the constitution of environmental issues as specific environ¬mental objects and objectives. EMS catalyzes alignmentprocesses that produce coherence among the different elements involved......, the networks of environmental professionals that work in the environmental organisation, in consulting and regulatory enforcement, and dominating business cultures. These have previously been identified in the literature as individually significant in relation to the evolving environmental agendas...... they are implemented in and how the changing context is reflected in the environmental objectives that are established and prioritised. Our argument is, that the ability of the standard to achieve an impact is dependant on the constitution of ’coherent’ environmental issues in the context, where the management system...

  17. Well-Defined Silica Grafted Molybdenum Bis(imido) Catalysts for Imine Metathesis Reactions

    Barman, Samir

    2017-04-06

    Novel site-isolated tetracoordinated molybdenum complexes possessing bis(imido) ligands, [(≡Si–O)2Mo(═NR)2] (R = t-Bu, 2,6-C6H3-i-Pr2), were immobilized on partially dehydroxylated silica (SiO2-200) by a rigorous surface organometallic chemistry protocol. The newly developed materials adorned with bis(imido) functional units, which were previously exploited mainly as spectator ligands on silica-supported olefin metathesis molybdenum catalysts, are found to be efficient heterogeneous catalytic systems for imine cross metathesis under mild conditions.

  18. Harvesting Covert Networks: The Case Study of the iMiner Database

    Memon, Nasrullah; Wiil, Uffe Kock; Alhajj, Reda

    2011-01-01

    was incorporated in the iMiner prototype tool, which makes use of investigative data mining techniques to analyse data. This paper will present the developed framework along with the form and structure of the terrorist data in the database. Selected cases will be referenced to highlight the effectiveness of the i...... collected by intelligence agencies and government organisations is inaccessible to researchers. To counter the information scarcity, we designed and built a database of terrorist-related data and information by harvesting such data from publicly available authenticated websites. The database...

  19. Well-Defined Silica Grafted Molybdenum Bis(imido) Catalysts for Imine Metathesis Reactions

    Barman, Samir; Merle, Nicolas; Minenkov, Yury; De Mallmann, Aimery; Samantaray, Manoja; Le Qué mé ner, Fré dé ric; Szeto, Kai C.; Abou-Hamad, Edy; Cavallo, Luigi; Taoufik, Mostafa; Basset, Jean-Marie

    2017-01-01

    Novel site-isolated tetracoordinated molybdenum complexes possessing bis(imido) ligands, [(≡Si–O)2Mo(═NR)2] (R = t-Bu, 2,6-C6H3-i-Pr2), were immobilized on partially dehydroxylated silica (SiO2-200) by a rigorous surface organometallic chemistry protocol. The newly developed materials adorned with bis(imido) functional units, which were previously exploited mainly as spectator ligands on silica-supported olefin metathesis molybdenum catalysts, are found to be efficient heterogeneous catalytic systems for imine cross metathesis under mild conditions.

  20. Synthesis and biology of cyclic imine toxins, an emerging class of potent, globally distributed marine toxins.

    Stivala, Craig E; Benoit, Evelyne; Aráoz, Rómulo; Servent, Denis; Novikov, Alexei; Molgó, Jordi; Zakarian, Armen

    2015-03-01

    From a small group of exotic compounds isolated only two decades ago, Cyclic Imine (CI) toxins have become a major class of marine toxins with global distribution. Their distinct chemical structure, biological mechanism of action, and intricate chemistry ensures that CI toxins will continue to be the subject of fascinating fundamental studies in the broad fields of chemistry, chemical biology, and toxicology. The worldwide occurrence of potent CI toxins in marine environments, their accumulation in shellfish, and chemical stability are important considerations in assessing risk factors for human health. This review article aims to provide an account of chemistry, biology, and toxicology of CI toxins from their discovery to the present day.

  1. A Highly Stereocontrolled, One-Pot Approach toward Pyrrolobenzoxazinones and Pyrroloquinazolinones through a Lewis Acid-Catalyzed [3 + 2]-Cycloannulation Process.

    Boomhoff, Michael; Ukis, Rostyslav; Schneider, Christoph

    2015-08-21

    We report herein a stereocontrolled [3 + 2]-cycloheteroannulation of bis-silyl dienediolate 1 with 2-aminobenzoic acid- and 2-aminobenzamide-derived imines to furnish highly substituted pyrrolo[1,2-a]benzoxazinones 3 and pyrrolo[1,2-a]quinazolinones 4, respectively, in good overall yields. This one-pot process rapidly generates molecular complexity and comprises a Lewis acid-catalyzed, vinylogous Mannich reaction of 1 followed by an intramolecular N,O-acetal- and N,N-aminal formation, respectively, which proceeds with good to excellent stereocontrol.

  2. Synthesis and reactions of imines of α,β-ethylenic silicon-containing aldehydes with complex metal hydrides

    Surnin, V.A.; Stadnichuk, M.D.

    1986-01-01

    Imines of 3-trimethylsilyl-2-propenal or its hydrocarbon analog are reduced chemoselectively at the C=N double bond by sodium borohydride. The direction of lithium aluminum hydride reduction of these imines is not influenced by the nature of the element attached to the C=C bond silicon versus carbon, but rather is determined by the nature of the radical group attached to the nitrogen atom; N-arylimines undergo addition with lithium aluminum hydride at the C=N bond exclusively, whereas for N-alkylimines the addition reactions occur either partially or in full in the 1,4-position, depending on the reaction conditions, to give imines of saturated aldehydes after demetallation

  3. Thermodynamics of ligand binding to acyl-coenzyme A binding protein studied by titration calorimetry

    Færgeman, Nils J.; Sigurskjold, B W; Kragelund, B B

    1996-01-01

    Ligand binding to recombinant bovine acyl-CoA binding protein (ACBP) was examined using isothermal microcalorimetry. Microcalorimetric measurements confirm that the binding affinity of acyl-CoA esters for ACBP is strongly dependent on the length of the acyl chain with a clear preference for acyl-...

  4. Acyl-CoA binding protein and epidermal barrier function

    Bloksgaard, Maria; Neess, Ditte; Færgeman, Nils J

    2014-01-01

    The acyl-CoA binding protein (ACBP) is a 10kDa intracellular protein expressed in all eukaryotic species and mammalian tissues investigated. It binds acyl-CoA esters with high specificity and affinity and is thought to act as an intracellular transporter of acyl-CoA esters between different...... includes tousled and greasy fur, development of alopecia and scaling of the skin with age. Furthermore, epidermal barrier function is compromised causing a ~50% increase in transepidermal water loss relative to that of wild type mice. Lipidomic analyses indicate that this is due to significantly reduced...

  5. Synthesis and characterization of two new TiO2-containing benzothiazole-based imine composites for organic device applications.

    Różycka, Anna; Iwan, Agnieszka; Bogdanowicz, Krzysztof Artur; Filapek, Michal; Górska, Natalia; Pociecha, Damian; Malinowski, Marek; Fryń, Patryk; Hreniak, Agnieszka; Rysz, Jakub; Dąbczyński, Paweł; Marzec, Monika

    2018-01-01

    The effect of the presence of titanium dioxide in two new imines, ( E , E )-(butane-1,4-diyl)bis(oxybutane-4,1-diyl) bis(4-{[(benzo[ d ][1,3]thiazol-2-yl)methylidene]amino}benzoate) (SP1) and ( E )- N -[(benzo[ d ][1,3]thiazol-2-yl)methylidene]-4-dodecylaniline (SP2), on the properties and stability of imine:TiO 2 composites for organic device applications were examined. The investigated titanium dioxide (in anatase form, obtained via the sol-gel method) exhibited a surface area of 59.5 m 2 /g according to Brunauer-Emmett-Teller theory, and its structure is a combination of both meso- and microporous. The average pore diameter calculated by the Barrett-Joyner-Halenda method was 6.2 nm and the cumulative volume of pores was 0.117 m 3 /g. The imine SP1 exhibited columnar organization (Col), while SP2 revealed a hexagonal columnar crystalline phase (Col hk ). The imine:TiO 2 mixtures in various weight ratio (3:0, 3:1, 3:2, 3:3) showed a lower energy gap and HOMO-LUMO energy levels compared to pure TiO 2 . This implies that TiO 2 provides not only a larger surface area for sensitizer adsorption and good electron collection, but also causes a shift of the imine energy levels resulting from intermolecular interaction. Also the temperature of the phase transition was slightly affected with the increase of TiO 2 concentration in imine-based composites. The changes observed in the Fourier transform middle-infrared absorption (FT-MIR) spectra confirmed the significant influence of TiO 2 on structural properties of both investigated imines. Similar interactions of oxygen vacancies existing on the TiO 2 surface with SP1 and SP2 were observed. The imine:TiO 2 mixtures showed good air stability and reusability, which demonstrates its potential for organic device applications.

  6. Synthesis and characterization of two new TiO2-containing benzothiazole-based imine composites for organic device applications

    Różycka, Anna; Bogdanowicz, Krzysztof Artur; Filapek, Michal; Górska, Natalia; Pociecha, Damian; Malinowski, Marek; Fryń, Patryk; Hreniak, Agnieszka; Rysz, Jakub; Dąbczyński, Paweł

    2018-01-01

    The effect of the presence of titanium dioxide in two new imines, (E,E)-(butane-1,4-diyl)bis(oxybutane-4,1-diyl) bis(4-{[(benzo[d][1,3]thiazol-2-yl)methylidene]amino}benzoate) (SP1) and (E)-N-[(benzo[d][1,3]thiazol-2-yl)methylidene]-4-dodecylaniline (SP2), on the properties and stability of imine:TiO2 composites for organic device applications were examined. The investigated titanium dioxide (in anatase form, obtained via the sol–gel method) exhibited a surface area of 59.5 m2/g according to Brunauer–Emmett–Teller theory, and its structure is a combination of both meso- and microporous. The average pore diameter calculated by the Barrett–Joyner–Halenda method was 6.2 nm and the cumulative volume of pores was 0.117 m3/g. The imine SP1 exhibited columnar organization (Col), while SP2 revealed a hexagonal columnar crystalline phase (Colhk). The imine:TiO2 mixtures in various weight ratio (3:0, 3:1, 3:2, 3:3) showed a lower energy gap and HOMO–LUMO energy levels compared to pure TiO2. This implies that TiO2 provides not only a larger surface area for sensitizer adsorption and good electron collection, but also causes a shift of the imine energy levels resulting from intermolecular interaction. Also the temperature of the phase transition was slightly affected with the increase of TiO2 concentration in imine-based composites. The changes observed in the Fourier transform middle-infrared absorption (FT-MIR) spectra confirmed the significant influence of TiO2 on structural properties of both investigated imines. Similar interactions of oxygen vacancies existing on the TiO2 surface with SP1 and SP2 were observed. The imine:TiO2 mixtures showed good air stability and reusability, which demonstrates its potential for organic device applications. PMID:29600135

  7. Mild Palladium Catalyzed ortho C-H Bond Functionalizations of Aniline Derivatives.

    Tischler, Ms Orsolya; Tóth, Mr Balázs; Novák, Zoltán

    2017-02-01

    This account collects the developments and transformations which avoid the utilization of harsh reaction conditions in the field of palladium catalyzed, ortho-directed C-H activation of aniline derivatives from the first attempts to up-to-date results, including the results of our research laboratory. The discussed functionalizations performed under mild conditions include acylation, olefination, arylation, alkylation, alkoxylation reactions. Beside the optimization studies and the synthetic applications mechanistic investigations are also presented. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Selective biocatalytic acylation studies on 5′-O-(4,4′-Dimethoxytrityl)-2′,3′-Secouridine

    Singh, Sunil K.; Reddy, L. Chandrashekhar; Srivastava, Smriti

    2012-01-01

    Lipozyme® TL IM (Theremomyces lanuginosus lipase immobilized on silica) in toluene catalyzes the acylation of the 2( )'-OH over the 3( )'-OH group in 5( )'-O-(4,4( )'-dimethoxytrityl)-2( )',3( )'-secouridine (5( )'-O-DMT-2( )',3( )'-secouridine) in a highly selective fashion in moderate to almost...... quantitative yields. The turn over during benzoyl transfer reactions mediated by vinyl benzoate or benzoic anhydride was faster than in acyl transfer reactions with vinyl acetate or C(1) to C(5) acid anhydrides; except in the case of butanoic anhydride. The 2( )'-O-benzoyl-5( )'-O-DMT-2( )',3( )'-secouridine...

  9. Nanomechanical properties of hydroxyapatite (HAP) with DAB dendrimers (poly-propylene imine) coatings onto titanium surfaces

    Charitidis, Costas A.; Skarmoutsou, Amalia; Tsetsekou, Athena; Brasinika, Despina; Tsiourvas, Dimitris

    2013-01-01

    Highlights: ► The synthesis of hydroxyapatite (HAP) nanoparticles in the presence of a cationic fourth generation diaminobutane poly(propylene imine) dendrimer (DAB). ► The nanomechanical properties of different HAP-DAB coatings onto titanium surfaces. ► Wear resistance and adhesion properties of the synthesized coatings quantified by nanoindentation data analysis. -- Abstract: Coatings of hydroxyapatite (HAP) nanorods onto titanium surfaces were synthesized with the aim to improve coatings’ mechanical properties and adhesion to the substrate. The coatings are consisting of HAP nanorods synthesized in the presence of a cationic fourth generation diaminobutane poly(propylene imine) dendrimer (DAB) bearing 32 amine end groups employing varying calcium: dendrimer ratios and varying hydrothermal treatments. The quality, surface morphology and structure of the coatings were characterized with X-ray diffraction, thermogravimetric analysis, scanning electron microscopy and energy dispersive microanalysis. Wear resistance and adhesion properties of the coatings onto titanium substrates were studied through nanoindentation analysis. The experimental conditions, namely the calcium: dendrimer molar ratio and the hydrothermal treatment temperature were carefully selected; thus, it was possible to produce coatings of high hardness and elastic modulus values (ranging between 1–4.5 GPa and 40–150 GPa, respectively) and/or high wear resistance and plastic deformation values

  10. A catalyst-free addition reaction of zinc amide enolates to N-sulfonyle imines

    Joo, Seong Ryu; Im, Pyeong Won; Kim, Jong Sung; Kim, Seung Hoi [Dept. of Chemistry, Dankook University, Cheonan (Korea, Republic of); Park Soo Youl [Interface Chemistry and Engineering Research Team, Korea Research Institute of Chemical Technology, Daejon (Korea, Republic of)

    2016-12-15

    Despite the remarkable expansion of the imino-Reformatsky reaction, one interesting aspect is that, to the best of our knowledge, zinc enolates derived solely from α-halo esters have been mainly used in the recent progress. In contrast, a few limited examples have been reported concerning the application of zinc enolates derived from α-halo amide to the imino-Reformatsky reaction. In recent years, Rodriguez-Solla and co-workers reported the addition reaction of samarium enolates derived from both α-halo esters and amides to imines, resulting in the synthe- sis of β-amino esters or amides. In conclusion, we established a potential synthetic proto- col for the preparation of β-amino amides. This work was accomplished by the direct addition of zinc amide enolates to N-sulfonyl imines in the absence of any metal-catalyst under mild conditions. Due to the operational simplicity of the proposed method, it can be further utilized in synthetic organic chemistry. Further studies to elucidate the scope of this approach are currently underway in our laboratory.

  11. A catalyst-free addition reaction of zinc amide enolates to N-sulfonyle imines

    Joo, Seong Ryu; Im, Pyeong Won; Kim, Jong Sung; Kim, Seung Hoi; Park Soo Youl

    2016-01-01

    Despite the remarkable expansion of the imino-Reformatsky reaction, one interesting aspect is that, to the best of our knowledge, zinc enolates derived solely from α-halo esters have been mainly used in the recent progress. In contrast, a few limited examples have been reported concerning the application of zinc enolates derived from α-halo amide to the imino-Reformatsky reaction. In recent years, Rodriguez-Solla and co-workers reported the addition reaction of samarium enolates derived from both α-halo esters and amides to imines, resulting in the synthe- sis of β-amino esters or amides. In conclusion, we established a potential synthetic proto- col for the preparation of β-amino amides. This work was accomplished by the direct addition of zinc amide enolates to N-sulfonyl imines in the absence of any metal-catalyst under mild conditions. Due to the operational simplicity of the proposed method, it can be further utilized in synthetic organic chemistry. Further studies to elucidate the scope of this approach are currently underway in our laboratory

  12. Polyethylene imine modified hydrochar adsorption for chromium (VI) and nickel (II) removal from aqueous solution.

    Shi, Yuanji; Zhang, Tao; Ren, Hongqiang; Kruse, Andrea; Cui, Ruofan

    2018-01-01

    An adsorbent hydrochar was synthesized from corn cobs and modified with polyethylene imine (PEI). The hydrochars before and after modification were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis. FTIR and XPS revealed that the PEI was grafted onto the hydrochar via ether and imine bonds formed with glutaraldehyde. The maximum adsorption capacities for Cr(VI) (33.663mg/g) and Ni(II) (29.059mg/g) on the modified hydrochars were 365% and 43.7% higher, respectively, than those on the unmodified hydrochar. A pseudo-second-order model described the adsorption of Ni(II) and Cr(VI) on all the adsorbents. The adsorption of Cr(VI) was endothermic, spontaneous, increased disorder, and obeyed the Langmuir model. By contrast, the adsorption of Ni(II) was exothermic, spontaneous, decreased disorder, and obeyed the Freundlich model. XPS confirmed that the adsorption sites and mechanisms for Ni(II) and Cr(VI) on the modified hydrochars were different. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Nanomechanical properties of hydroxyapatite (HAP) with DAB dendrimers (poly-propylene imine) coatings onto titanium surfaces

    Charitidis, Costas A., E-mail: charitidis@chemeng.ntua.gr [School of Chemical Engineering, National Technical University of Athens, Iroon Polytechniou, Zografou, 15780 Athens (Greece); Skarmoutsou, Amalia [School of Chemical Engineering, National Technical University of Athens, Iroon Polytechniou, Zografou, 15780 Athens (Greece); Tsetsekou, Athena; Brasinika, Despina [School of Mining Engineering and Metallurgy, National Technical University of Athens, Iroon Polytechniou, Zografou, 15780 Athens (Greece); Tsiourvas, Dimitris [National Centre for Scientific Research “Demokritos”, Institute of Physical Chemistry, Agia Paraskevi, 15310 Athens (Greece)

    2013-04-20

    Highlights: ► The synthesis of hydroxyapatite (HAP) nanoparticles in the presence of a cationic fourth generation diaminobutane poly(propylene imine) dendrimer (DAB). ► The nanomechanical properties of different HAP-DAB coatings onto titanium surfaces. ► Wear resistance and adhesion properties of the synthesized coatings quantified by nanoindentation data analysis. -- Abstract: Coatings of hydroxyapatite (HAP) nanorods onto titanium surfaces were synthesized with the aim to improve coatings’ mechanical properties and adhesion to the substrate. The coatings are consisting of HAP nanorods synthesized in the presence of a cationic fourth generation diaminobutane poly(propylene imine) dendrimer (DAB) bearing 32 amine end groups employing varying calcium: dendrimer ratios and varying hydrothermal treatments. The quality, surface morphology and structure of the coatings were characterized with X-ray diffraction, thermogravimetric analysis, scanning electron microscopy and energy dispersive microanalysis. Wear resistance and adhesion properties of the coatings onto titanium substrates were studied through nanoindentation analysis. The experimental conditions, namely the calcium: dendrimer molar ratio and the hydrothermal treatment temperature were carefully selected; thus, it was possible to produce coatings of high hardness and elastic modulus values (ranging between 1–4.5 GPa and 40–150 GPa, respectively) and/or high wear resistance and plastic deformation values.

  14. Acyl Meldrum's acid derivatives: application in organic synthesis

    Janikowska, K.; Rachoń, J.; Makowiec, S.

    2014-07-01

    This review is focused on an important class of Meldrum's acid derivatives commonly known as acyl Meldrum's acids. The preparation methods of these compounds are considered including the recently proposed and rather rarely used ones. The chemical properties of acyl Meldrum's acids are described in detail, including thermal stability and reactions with various nucleophiles. The possible mechanisms of these transformations are analyzed. The bibliography includes 134 references.

  15. Catalyzed deuterium fueled tokamak reactors

    Southworth, F.H.

    1977-01-01

    Catalyzed deuterium fuel presents several advantages relative to D-T. These are, freedom from tritium breeding, high charged particle power fraction and lowered neutron energy deposition in the blanket. Higher temperature operation, lower power densities and increased confinement are simultaneously required. However, the present study has developed designs which have capitalized upon the advantages of catalyzed deuterium to overcome the difficulties associated with the fuel while obtaining high efficiency

  16. Acyl-CoA-binding protein (ACBP) can mediate intermembrane acyl-CoA transport and donate acyl-CoA for beta-oxidation and glycerolipid synthesis

    Rasmussen, J T; Færgeman, Nils J.; Kristiansen, K

    1994-01-01

    The dissociation constants for octanoyl-CoA, dodecanoyl-CoA and hexadecanoyl-CoA binding to acyl-CoA-binding protein (ACBP) were determined by using titration microcalorimetry. The KD values obtained, (0.24 +/- 0.02) x 10(-6) M, (0.65 +/- 0.2) x 10(-8) M and (0.45 +/- 0.2) x 10(-13) M respectively......, were much lower than expected. ACBP was able to extract hexadecanoyl-CoA from phosphatidylcholine membranes immobilized on a nitrocellulose membrane. The acyl-CoA/ACBP complex formed was able to transport acyl-CoA to mitochondria or microsomes in suspension, or to microsomes immobilized...

  17. Large-scale ruthenium- and enzyme-catalyzed dynamic kinetic resolution of (rac-1-phenylethanol

    Bäckvall Jan-E

    2007-12-01

    Full Text Available Abstract The scale-up of the ruthenium- and enzyme-catalyzed dynamic kinetic resolution (DKR of (rac-1-phenylethanol (2 is addressed. The immobilized lipase Candida antarctica lipase B (CALB was employed for the resolution, which shows high enantioselectivity in the transesterification. The ruthenium catalyst used, (η 5-C5Ph5RuCl(CO2 1, was shown to possess very high reactivity in the "in situ" redox racemization of 1-phenylethanol (2 in the presence of the immobilized enzyme, and could be used in 0.05 mol% with high efficiency. Commercially available isopropenyl acetate was employed as acylating agent in the lipase-catalyzed transesterifications, which makes the purification of the product very easy. In a successful large-scale DKR of 2, with 0.05 mol% of 1, (R-1-phenylethanol acetate (3 was obtained in 159 g (97% yield in excellent enantiomeric excess (99.8% ee.

  18. A Highly Stable Microporous Covalent Imine Network Adsorbent for Natural Gas Upgrading and Flue Gas CO2 Capture

    Das, Swapan Kumar; Wang, Xinbo; Ostwal, Mayur; Lai, Zhiping

    2016-01-01

    The feasible capture and separation of CO2 and N2 from CH4 is an important task for natural gas upgrading and the control of greenhouse gas emissions. Here, we studied the microporous covalent imine networks (CIN) material prepared through Schiff

  19. Synthesis of N-substituted a,a-difluoro-b-aminophosphonates by addition of diethyl lithiodifluoromethylphosphonate to imines

    Cherkupally, Prabhakar; Beier, Petr

    2012-01-01

    Roč. 141, Sep (2012), s. 76-82 ISSN 0022-1139 R&D Projects: GA ČR GP203/08/P310 Institutional support: RVO:61388963 Keywords : nucleophilic addition * difluorophosphonate * aminophosphonate * imines Subject RIV: CC - Organic Chemistry Impact factor: 1.939, year: 2012

  20. Effect of aluminum alkyls on a homogeneous and silica-supported phenoxy-imine titanium catalyst for ethylene trimerization

    Karbach, Fabian F.; Severn, John R.; Duchateau, Robbert

    A phenoxy-imine titanium catalyst (FI-catalyst) for selective ethylene trimerization was immobilized on methyl aluminoxane (MAO) pretreated silica and its activity and selectivity was compared with that of the corresponding homogeneous catalyst system. The homogeneous and heterogeneous ethylene

  1. Hydrogenation of imines catalysed by ruthenium(II) complexes based on lutidine-derived CNC pincer ligands.

    Hernández-Juárez, Martín; Vaquero, Mónica; Álvarez, Eleuterio; Salazar, Verónica; Suárez, Andrés

    2013-01-14

    The preparation of new Ru(II) complexes incorporating fac-coordinated lutidine-derived CNC ligands is reported. These derivatives are selectively deprotonated by (t)BuOK at one of the methylene arms of the pincer, leading to catalytically active species in the hydrogenation of imines.

  2. Azeotropic Preparation of a "C"-Phenyl "N"-Aryl Imine: An Introductory Undergraduate Organic Chemistry Laboratory Experiment

    Silverberg, Lee J.; Coyle, David J.; Cannon, Kevin C.; Mathers, Robert T.; Richards, Jeffrey A.; Tierney, John

    2016-01-01

    Imines are important in biological chemistry and as intermediates in organic synthesis. An experiment for introductory undergraduate organic chemistry is presented in which benzaldehyde was condensed with "p"-methoxyaniline in toluene to give 4-methoxy-"N"-(phenylmethylene)benzenamine. Water was removed by azeotropic…

  3. Multivalent contrast agents based on Gd-DTPA-terminated poly (propylene imine) dendrimers for Magnetic Resonance Imaging

    Langereis, S.; Lussanet, de Q.G; Genderen, van M.H.P.; Backes, W.H.; Meijer, E.W.

    2004-01-01

    A convenient methodol. has been developed for the synthesis of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-terminated poly(propylene imine) dendrimers as contrast agents for magnetic resonance imaging (MRI). In our strategy, isocyanate-activated, tert-butyl-protected DTPA analogs were

  4. Mechanism of intermolecular hydroacylation of vinylsilanes catalyzed by a rhodium(I) olefin complex: a DFT study.

    Meng, Qingxi; Shen, Wei; Li, Ming

    2012-03-01

    Density functional theory (DFT) was used to investigate the Rh(I)-catalyzed intermolecular hydroacylation of vinylsilane with benzaldehyde. All intermediates and transition states were optimized completely at the B3LYP/6-31G(d,p) level (LANL2DZ(f) for Rh). Calculations indicated that Rh(I)-catalyzed intermolecular hydroacylation is exergonic, and the total free energy released is -110 kJ mol(-1). Rh(I)-catalyzed intermolecular hydroacylation mainly involves the active catalyst CA2, rhodium-alkene-benzaldehyde complex M1, rhodium-alkene-hydrogen-acyl complex M2, rhodium-alkyl-acyl complex M3, rhodium-alkyl-carbonyl-phenyl complex M4, rhodium-acyl-phenyl complex M5, and rhodium-ketone complex M6. The reaction pathway CA2 + R2 → M1b → T1b → M2b → T2b1 → M3b1 → T4b → M4b → T5b → M5b → T6b → M6b → P2 is the most favorable among all reaction channels of Rh(I)-catalyzed intermolecular hydroacylation. The reductive elimination reaction is the rate-determining step for this pathway, and the dominant product predicted theoretically is the linear ketone, which is consistent with Brookhart's experiments. Solvation has a significant effect, and it greatly decreases the free energies of all species. The use of the ligand Cp' (Cp' = C(5)Me(4)CF(3)) decreased the free energies in general, and in this case the rate-determining step was again the reductive elimination reaction.

  5. Transition-Metal-Controlled Inorganic Ligand-Supported Non-Precious Metal Catalysts for the Aerobic Oxidation of Amines to Imines.

    Yu, Han; Zhai, Yongyan; Dai, Guoyong; Ru, Shi; Han, Sheng; Wei, Yongge

    2017-10-09

    Most state-of-art transition-metal catalysts usually require organic ligands, which are essential for controlling the reactivity and selectivity of reactions catalyzed by transition metals. However, organic ligands often suffer from severe problems including cost, toxicity, air/moisture sensitivity, and being commercially unavailable. Herein, we show a simple, mild, and efficient aerobic oxidation procedure of amines using inorganic ligand-supported non-precious metal catalysts 1, (NH 4 ) n [MMo 6 O 18 (OH) 6 ] (M=Cu 2+ ; Fe 3+ ; Co 3+ ; Ni 2+ ; Zn 2+ , n=3 or 4), synthesized by a simple one-step method in water at 100 °C, demonstrating that the catalytic activity and selectivity can be significantly improved by changing the central metal atom. In the presence of these catalysts, the catalytic oxidation of primary and secondary amines, as well as the coupling of alcohols and amines, can smoothly proceed to afford various imines with O 2 (1 atm) as the sole oxidant. In particular, the catalysts 1 have transition-metal ion core, and the planar arrangement of the six Mo VI centers at their highest oxidation states around the central heterometal can greatly enhance the Lewis acidity of catalytically active sites, and also enable the electrons in the center to delocalize onto the six edge-sharing MO 6 units, in the same way as ligands in traditional organometallic complexes. The versatility of this methodology maybe opens a path to catalytic oxidation through inorganic ligand-coordinated metal catalysis. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Involvement of PlsX and the acyl-phosphate dependent sn-glycerol-3-phosphate acyltransferase PlsY in the initial stage of glycerolipid synthesis in Bacillus subtilis.

    Hara, Yoshinori; Seki, Masahide; Matsuoka, Satoshi; Hara, Hiroshi; Yamashita, Atsushi; Matsumoto, Kouji

    2008-12-01

    The gene responsible for the first acylation of sn-glycerol-3-phosphate (G3P) in Bacillus subtilis has not yet been determined with certainty. The product of this first acylation, lysophosphatidic acid (LPA), is subsequently acylated again to form phosphatidic acid (PA), the primary precursor to membrane glycerolipids. A novel G3P acyltransferase (GPAT), the gene product of plsY, which uses acyl-phosphate formed by the plsX gene product, has recently been found to synthesize LPA in Streptococcus pneumoniae. We found that in B. subtilis growth arrests after repression of either a plsY homologue or a plsX homologue were overcome by expression of E. coli plsB, which encodes an acyl-acylcarrier protein (acyl-ACP)-dependent GPAT, although in the case of plsX repression a high level of plsB expression was required. B. subtilis has, therefore, a capability to use the acyl-ACP dependent GPAT of PlsB. Simultaneous expression of plsY and plsX suppressed the glycerol requirement of a strict glycerol auxotrophic derivative of the E. coli plsB26 mutant, although either one alone did not. Membrane fractions from B. subtilis cells catalyzed palmitoylphosphate-dependent acylation of [14C]-labeled G3P to synthesize [14C]-labeled LPA, whereas those from DeltaplsY cells did not. The results indicate unequivocally that PlsY is an acyl-phosphate dependent GPAT. Expression of plsX corrected the glycerol auxotrophy of a DeltaygiH (the deleted allele of an E. coli homologue of plsY) derivative of BB26-36 (plsB26 plsX50), suggesting an essential role of plsX other than substrate supply for acyl-phosphate dependent LPA synthesis. Two-hybrid examinations suggested that PlsY is associated with PlsX and that each may exist in multimeric form.

  7. Structural insights into GDP-mediated regulation of a bacterial acyl-CoA thioesterase.

    Khandokar, Yogesh B; Srivastava, Parul; Cowieson, Nathan; Sarker, Subir; Aragao, David; Das, Shubagata; Smith, Kate M; Raidal, Shane R; Forwood, Jade K

    2017-12-15

    Thioesterases catalyze the cleavage of thioester bonds within many activated fatty acids and acyl-CoA substrates. They are expressed ubiquitously in both prokaryotes and eukaryotes and are subdivided into 25 thioesterase families according to their catalytic active site, protein oligomerization, and substrate specificity. Although many of these enzyme families are well-characterized in terms of function and substrate specificity, regulation across most thioesterase families is poorly understood. Here, we characterized a TE6 thioesterase from the bacterium Neisseria meningitidis Structural analysis with X-ray crystallographic diffraction data to 2.0-Å revealed that each protein subunit harbors a hot dog-fold and that the TE6 enzyme forms a hexamer with D3 symmetry. An assessment of thioesterase activity against a range of acyl-CoA substrates revealed the greatest activity against acetyl-CoA, and structure-guided mutagenesis of putative active site residues identified Asn 24 and Asp 39 as being essential for activity. Our structural analysis revealed that six GDP nucleotides bound the enzyme in close proximity to an intersubunit disulfide bond interactions that covalently link thioesterase domains in a double hot dog dimer. Structure-guided mutagenesis of residues within the GDP-binding pocket identified Arg 93 as playing a key role in the nucleotide interaction and revealed that GDP is required for activity. All mutations were confirmed to be specific and not to have resulted from structural perturbations by X-ray crystallography. This is the first report of a bacterial GDP-regulated thioesterase and of covalent linkage of thioesterase domains through a disulfide bond, revealing structural similarities with ADP regulation in the human ACOT12 thioesterase. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Regioselective Acylation of Diols and Triols: The Cyanide Effect.

    Peng, Peng; Linseis, Michael; Winter, Rainer F; Schmidt, Richard R

    2016-05-11

    Central topics of carbohydrate chemistry embrace structural modifications of carbohydrates and oligosaccharide synthesis. Both require regioselectively protected building blocks that are mainly available via indirect multistep procedures. Hence, direct protection methods targeting a specific hydroxy group are demanded. Dual hydrogen bonding will eventually differentiate between differently positioned hydroxy groups. As cyanide is capable of various kinds of hydrogen bonding and as it is a quite strong sterically nondemanding base, regioselective O-acylations should be possible at low temperatures even at sterically congested positions, thus permitting formation and also isolation of the kinetic product. Indeed, 1,2-cis-diols, having an equatorial and an axial hydroxy group, benzoyl cyanide or acetyl cyanide as an acylating agent, and DMAP as a catalyst yield at -78 °C the thermodynamically unfavorable axial O-acylation product; acyl migration is not observed under these conditions. This phenomenon was substantiated with 3,4-O-unproteced galacto- and fucopyranosides and 2,3-O-unprotected mannopyranosides. Even for 3,4,6-O-unprotected galactopyranosides as triols, axial 4-O-acylation is appreciably faster than O-acylation of the primary 6-hydroxy group. The importance of hydrogen bonding for this unusual regioselectivity could be confirmed by NMR studies and DFT calculations, which indicate favorable hydrogen bonding of cyanide to the most acidic axial hydroxy group supported by hydrogen bonding of the equatorial hydroxy group to the axial oxygen. Thus, the "cyanide effect" is due to dual hydrogen bonding of the axial hydroxy group which enhances the nucleophilicity of the respective oxygen atom, permitting an even faster reaction for diols than for mono-ols. In contrast, fluoride as a counterion favors dual hydrogen bonding to both hydroxy groups leading to equatorial O-acylation.

  9. Rh(III)-Catalyzed Synthesis of N-Unprotected Indoles from Imidamides and Diazo Ketoesters via C-H Activation and C-C/C-N Bond Cleavage.

    Qi, Zisong; Yu, Songjie; Li, Xingwei

    2016-02-19

    The synthesis of N-unprotected indoles has been realized via Rh(III)-catalyzed C-H activation/annulation of imidamides with α-diazo β-ketoesters. The reaction occurs with the release of an amide coproduct, which originates from both the imidamide and the diazo as a result of C═N cleavage of the imidamide and C-C(acyl) cleavage of the diazo. A rhodacyclic intermediate has been isolated and a plausible mechanism has been proposed.

  10. Poly(Propylene Imine Dendrimers and Amoxicillin as Dual-Action Antibacterial Agents

    Natalia Wrońska

    2015-10-01

    Full Text Available Besides acting as antimicrobial compounds, dendrimers can be considered as agents that improve the therapeutic effectiveness of existing antibiotics. In this work we present a new approach to using amoxicillin (AMX against reference strains of common Gram-negative pathogens, alone and in combination with poly(propylene imine (PPI dendrimers, or derivatives thereof, in which 100% of the available hydrogen atoms are substituted with maltose (PPI 100%malG3. The concentrations of dendrimers used remained in the range non-toxic to eukaryotic cells. The results indicate that PPI dendrimers significantly enhance the antibacterial effect of amoxicillin alone, allowing antibiotic doses to be reduced. It is important to reduce doses of amoxicillin because its widespread use in medicine could lead to the development of bacterial resistance and environmental pollution. This is the first report on the combined antibacterial activity of PPI surface-modified maltose dendrimers and amoxicillin.

  11. Interactive transport of guanidinylated poly(propylene imine)-based dendrimers through liposomal and cellular membranes.

    Tsogas, Ioannis; Sideratou, Zili; Tsiourvas, Dimitris; Theodossiou, Theodossis A; Paleos, Constantinos M

    2007-10-15

    The ability of guanidinylated poly(propylene imine) dendrimers to translocate across lipid bilayers was assessed by employing either a model phosphate-bearing liposomal membrane system or A549 human lung carcinoma cells. Two dendrimer generations, differing in the number of surface guanidinium groups, were employed, while surface acetylation or the use of spacers affected the binding of the guanidinium group to the phosphate moiety and finally the transport efficiency. Following adhesion of dendrimers with liposomes, fusion or transport occurred. Transport through the liposomal bilayer was observed at low guanidinium/phosphate molar ratios, and was enhanced when the bilayer was in the liquid-crystalline phase. For effective transport through the liposomal membrane, an optimum balance between the binding strength and the degree of hydrophobicity of the guanidinylated dendrimer is required. In experiments performed in vitro with cells, efficient penetration and internalization in subcellular organelles and cytosol was observed.

  12. Photoprotection and the photophysics of acylated anthocyanins.

    da Silva, Palmira Ferreira; Paulo, Luísa; Barbafina, Adrianna; Eisei, Fausto; Quina, Frank H; Maçanita, António L

    2012-03-19

    The proposed role of anthocyanins in protecting plants against excess solar radiation is consistent with the occurrence of ultrafast (5-25 ps) excited-state proton transfer as the major de-excitation pathway of these molecules. However, because natural anthocyanins absorb mainly in the visible region of the spectra, with only a narrow absorption band in the UV-B region, this highly efficient deactivation mechanism would essentially only protect the plant from visible light. On the other hand, ground-state charge-transfer complexes of anthocyanins with naturally occurring electron-donor co-pigments, such as hydroxylated flavones, flavonoids, and hydroxycinnamic or benzoic acids, do exhibit high UV-B absorptivities that complement that of the anthocyanins. In this work, we report a comparative study of the photophysics of the naturally occurring anthocyanin cyanin, intermolecular cyanin-coumaric acid complexes, and an acylated anthocyanin, that is, cyanin with a pendant coumaric ester co-pigment. Both inter- and intramolecular anthocyanin-co-pigment complexes are shown to have ultrafast energy dissipation pathways comparable to those of model flavylium cation-co-pigment complexes. However, from the standpoint of photoprotection, the results indicate that the covalent attachment of co-pigment molecules to the anthocyanin represents a much more efficient strategy by providing the plant with significant UV-B absorption capacity and at the same time coupling this absorption to efficient energy dissipation pathways (ultrafast internal conversion of the complexed form and fast energy transfer from the excited co-pigment to the anthocyanin followed by adiabatic proton transfer) that avoid net photochemical damage. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Optimization of lipase-catalyzed synthesis of ginsenoside Rb1 esters using response surface methodology.

    Hu, Jiang-Ning; Lee, Jeung-Hee; Zhu, Xue-Mei; Shin, Jung-Ah; Adhikari, Prakash; Kim, Jae-Kyung; Lee, Ki-Teak

    2008-11-26

    In the lipase (Novozyme 435)-catalyzed synthesis of ginsenoside Rb1 esters, different acyl donors were found to affect not only the degree of conversion but also the regioselectivity. The reaction of acyl donors with short carbon chain was more effective, showing higher conversion than those with long carbon chain. Among the three solvent systems, the reaction in tert-amyl alcohol showed the highest conversion rate, while the reaction in the mixed solvent of t-BuOH and pyridine (1:1) had the lowest conversion rate. To allow the increase of GRb1 lipophilicity, we decided to further study the optimal condition of synthesis of GRb1 with vinyl decanoate with 10 carbon chain fatty acids in tert-amyl alcohol. Response surface methodology (RSM) was employed to optimize the synthesis condition. From the ridge analysis with maximum responses, the maximum GRb1 conversion was predicted to be 61.51% in a combination of factors (40.2 h, 52.95 degrees C, substrate mole ratio 275.57, and enzyme amount 39.81 mg/mL). Further, the adequacy of the predicted model was examined by additional independent experiments at the predicted maximum synthesis conditions. Results showed that the RSM was effective to optimize a combination of factors for lipase-catalyzed synthesis of ginsenoside Rb1 with vinyl decanoate.

  14. Lipase-catalyzed acyl exchange of soybean phosphatidylcholine in n-hexane: a critical evaluation of both acyl incorporation and product recovery

    Vikbjerg, Anders Falk; Mu, Huiling; Xu, Xuebing

    2005-01-01

    by hydrolysis, which led to the low yields. The biocatalyst used was the commercial immobilized lipase Lipozyme TL IM and substrates used were phosphatidylcholine (PC) from soybean and caprylic acid. A response surface design was used to evaluate the influence of selected parameters and their relationships...

  15. Synthesis and emulsifying properties of carbohydrate fatty acid esters produced from Agave tequilana fructans by enzymatic acylation.

    Casas-Godoy, Leticia; Arrizon, Javier; Arrieta-Baez, Daniel; Plou, Francisco J; Sandoval, Georgina

    2016-08-01

    Carbohydrate fatty acid esters are non-ionic surfactants with a broad spectrum of applications. These molecules are generally synthesized using short carbohydrates or linear fructans; however in this research carbohydrate fatty acid esters were produced for the first time with branched fructans from Agave tequilana. Using immobilized lipases we successfully acylated A. tequilana fructans with vinyl laurate, obtaining products with different degrees of polymerization (DP). Lipozyme 435 was the most efficient lipase to catalyze the transesterification reaction. HPLC and ESI-MS analysis proved the presence of a mixture of acylated products as a result of the chemical complexity of fructans in the A. tequilana. The ESI-MS spectra showed a molecular mass shift between 183 and 366g/mol for fructooligosaccharides with a DP lower than 6, which indicated the presence of Agave fructans that had been mono- and diacylated with lauric acid. The carbohydrate fatty acid esters (CFAE) obtained showed good emulsifying properties in W/O emulsions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. A high-performance liquid chromatography-based radiometric assay for acyl-CoA:alcohol transacylase from jojoba.

    Garver, W S; Kemp, J D; Kuehn, G D

    1992-12-01

    Acyl-CoA:alcohol transacylase catalyzes the final step in the biosynthesis of storage liquid wax esters from acyl-CoA fatty acids and fatty alcohols in a limited number of microbes, algae, and Simmondsia chinensis Link (jojoba). An improved and automated method of enzyme assay for this catalyst from cotyledons of jojoba is described. The assay method uses reversed-phase C18 high performance liquid chromatography (HPLC) to separate the labeled C30:1 liquid wax product, [14C]-dodecanyl-octadecenoate, from the unreacted substrate, [14C]octadecenoyl-CoA (oleyl-CoA), and other components produced from enzymes present in the crude homogenate of jojoba cotyledons, including [14C]-octadecenoic acid (oleic acid) and [14C]octadecenol (oleyol). Methods are also described for microscale chemical synthesis in one vessel of 14C-radiolabeled substrates and products for the transacylase. These labeled reagents are required to confirm the HPLC separations of reaction products. The radioactive components are quantitated using an on-line flow-through scintillation detector enabling sensitive and precise analysis of the reaction products.

  17. Expansion, retention and loss in the Acyl-CoA synthetase "Bubblegum" (Acsbg) gene family in vertebrate history.

    Lopes-Marques, Mónica; Machado, André M; Ruivo, Raquel; Fonseca, Elza; Carvalho, Estela; Castro, L Filipe C

    2018-07-20

    Fatty acids (FAs) constitute a considerable fraction of all lipid molecules with a fundamental role in numerous physiological processes. In animals, the majority of complex lipid molecules are derived from the transformation of FAs through several biochemical pathways. Yet, for FAs to enroll in these pathways they require an activation step. FA activation is catalyzed by the rate limiting action of Acyl-CoA synthases. Several Acyl-CoA enzyme families have been previously described and classified according to the chain length of FAs they process. Here, we address the evolutionary history of the ACSBG gene family which activates, FAs with >16 carbons. Currently, two different ACSBG gene families, ACSBG1 and ACSBG2, are recognized in vertebrates. We provide evidence that a wider and unequal ACSBG gene repertoire is present in vertebrate lineages. We identify a novel ACSBG-like gene lineage which occurs specifically in amphibians, ray finned fishes, coelacanths and cartilaginous fishes named ACSBG3. Also, we show that the ACSBG2 gene lineage duplicated in the Theria ancestor. Our findings, thus offer a far richer understanding on FA activation in vertebrates and provide key insights into the relevance of comparative and functional analysis to perceive physiological differences, namely those related with lipid metabolic pathways. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Remote control of regioselectivity in acyl-acyl carrier protein-desaturases.

    Guy, Jodie E; Whittle, Edward; Moche, Martin; Lengqvist, Johan; Lindqvist, Ylva; Shanklin, John

    2011-10-04

    Regiospecific desaturation of long-chain saturated fatty acids has been described as approaching the limits of the discriminatory power of enzymes because the substrate entirely lacks distinguishing features close to the site of dehydrogenation. To identify the elusive mechanism underlying regioselectivity, we have determined two crystal structures of the archetypal Δ9 desaturase from castor in complex with acyl carrier protein (ACP), which show the bound ACP ideally situated to position C9 and C10 of the acyl chain adjacent to the diiron active site for Δ9 desaturation. Analysis of the structures and modeling of the complex between the highly homologous ivy Δ4 desaturase and ACP, identified a residue located at the entrance to the binding cavity, Asp280 in the castor desaturase (Lys275 in the ivy desaturase), which is strictly conserved within Δ9 and Δ4 enzymes but differs between them. We hypothesized that interaction between Lys275 and the phosphate of the pantetheine, seen in the ivy model, is key to positioning C4 and C5 adjacent to the diiron center for Δ4 desaturation. Mutating castor Asp280 to Lys resulted in a major shift from Δ9 to Δ4 desaturation. Thus, interaction between desaturase side-chain 280 and phospho-serine 38 of ACP, approximately 27 Å from the site of double-bond formation, predisposes ACP binding that favors either Δ9 or Δ4 desaturation via repulsion (acidic side chain) or attraction (positively charged side chain), respectively. Understanding the mechanism underlying remote control of regioselectivity provides the foundation for reengineering desaturase enzymes to create designer chemical feedstocks that would provide alternatives to those currently obtained from petrochemicals.

  19. Metabolic alkene labeling and in vitro detection of histone acylation via the aqueous oxidative Heck reaction

    Ourailidou, Maria E; Dockerty, Paul; Witte, Martin; Poelarends, Gerrit J; Dekker, Frank J

    2015-01-01

    The detection of protein lysine acylations remains a challenge due to lack of specific antibodies for acylations with various chain lengths. This problem can be addressed by metabolic labeling techniques using carboxylates with reactive functionalities. Subsequent chemoselective reactions with a

  20. Identification of unusual phospholipid fatty acyl compositions of Acanthamoeba castellanii.

    Marta Palusinska-Szysz

    Full Text Available Acanthamoeba are opportunistic protozoan pathogens that may lead to sight-threatening keratitis and fatal granulomatous encephalitis. The successful prognosis requires early diagnosis and differentiation of pathogenic Acanthamoeba followed by aggressive treatment regimen. The plasma membrane of Acanthamoeba consists of 25% phospholipids (PL. The presence of C20 and, recently reported, 28- and 30-carbon fatty acyl residues is characteristic of amoeba PL. A detailed knowledge about this unusual PL composition could help to differentiate Acanthamoeba from other parasites, e.g. bacteria and develop more efficient treatment strategies. Therefore, the detailed PL composition of Acanthamoeba castellanii was investigated by 31P nuclear magnetic resonance spectroscopy, thin-layer chromatography, gas chromatography, high performance liquid chromatography and liquid chromatography-mass spectrometry. Normal and reversed phase liquid chromatography coupled with mass spectrometric detection was used for detailed characterization of the fatty acyl composition of each detected PL. The most abundant fatty acyl residues in each PL class were octadecanoyl (18∶0, octadecenoyl (18∶1 Δ9 and hexadecanoyl (16∶0. However, some selected PLs contained also very long fatty acyl chains: the presence of 28- and 30-carbon fatty acyl residues was confirmed in phosphatidylethanolamine (PE, phosphatidylserine, phosphatidic acid and cardiolipin. The majority of these fatty acyl residues were also identified in PE that resulted in the following composition: 28∶1/20∶2, 30∶2/18∶1, 28∶0/20∶2, 30∶2/20∶4 and 30∶3/20∶3. The PL of amoebae are significantly different in comparison to other cells: we describe here for the first time unusual, very long chain fatty acids with Δ5-unsaturation (30∶35,21,24 and 30∶221,24 localized exclusively in specific phospholipid classes of A. castellanii protozoa that could serve as specific biomarkers for the presence of

  1. Caveolar fatty acids and acylation of caveolin-1.

    Qian Cai

    Full Text Available Caveolae are cholesterol and sphingolipids rich subcellular domains on plasma membrane. Caveolae contain a variety of signaling proteins which provide platforms for signaling transduction. In addition to enriched with cholesterol and sphingolipids, caveolae also contain a variety of fatty acids. It has been well-established that acylation of protein plays a pivotal role in subcellular location including targeting to caveolae. However, the fatty acid compositions of caveolae and the type of acylation of caveolar proteins remain largely unknown. In this study, we investigated the fatty acids in caveolae and caveolin-1 bound fatty acids.Caveolae were isolated from Chinese hamster ovary (CHO cells. The caveolar fatty acids were extracted with Folch reagent, methyl esterificated with BF3, and analyzed by gas chromatograph-mass spectrometer (GC/MS. The caveolin-1 bound fatty acids were immunoprecipitated by anti-caveolin-1 IgG and analyzed with GC/MS.In contrast to the whole CHO cell lysate which contained a variety of fatty acids, caveolae mainly contained three types of fatty acids, 0.48 µg palmitic acid, 0.61 µg stearic acid and 0.83 µg oleic acid/caveolae preparation/5 × 10(7 cells. Unexpectedly, GC/MS analysis indicated that caveolin-1 was not acylated by myristic acid; instead, it was acylated by palmitic acid and stearic acid.Caveolae contained a special set of fatty acids, highly enriched with saturated fatty acids, and caveolin-1 was acylated by palmitic acid and stearic acid. The unique fatty acid compositions of caveolae and acylation of caveolin-1 may be important for caveolae formation and for maintaining the function of caveolae.

  2. Studies on acylation of lysolecithin in chicken intestine

    Lokesh, B.R.; Madhava Rao, A.; Murthy, S.K.

    1976-01-01

    The enzymatic acylation of lysolecithin to lecithin is shown to occur in the brush border-free particulate fraction of the small intestines of neonatal chicken. It requires ATP, coenzyme A and Mg 2+ or Mn 2+ for maximal activity. The system is specific for oleic acid. The fatty acid composition at the α-position of lysolecithin does not seem to influence the rate of acylation. The fatty acid incorporated into lysolecithin is shown to occupy exclusively, the β-position. [ 32 P]lecithin and [1- 14 C]oleic acid has been used as tracers in the studies. (author)

  3. Enhancing the muon-catalyzed fusion yield

    Jones, S.E.

    1987-01-01

    Much has been learned about muon-catalyzed fusion since the last conference on emerging nuclear energy systems. Here the authors consider what they have learned about enhancing the muon-catalyzed fusion energy yield

  4. Structural properties of pepsin-solubilized collagen acylated by lauroyl chloride along with succinic anhydride

    Li, Conghu; Tian, Zhenhua; Liu, Wentao; Li, Guoying

    2015-01-01

    The structural properties of pepsin-solubilized calf skin collagen acylated by lauroyl chloride along with succinic anhydride were investigated in this paper. Compared with native collagen, acylated collagen retained the unique triple helix conformation, as determined by amino acid analysis, circular dichroism and X-ray diffraction. Meanwhile, the thermostability of acylated collagen using thermogravimetric measurements was enhanced as the residual weight increased by 5%. With the temperature increased from 25 to 115 °C, the secondary structure of native and acylated collagens using Fourier transform infrared spectroscopy measurements was destroyed since the intensity of the major amide bands decreased and the positions of the major amide bands shifted to lower wavenumber, respectively. Meanwhile, two-dimensional correlation spectroscopy revealed that the most sensitive bands for acylated and native collagens were amide I and II bands, respectively. Additionally, the corresponding order of the groups between native and acylated collagens was different and the correlation degree for acylated collagen was weaker than that of native collagen, suggesting that temperature played a small influence on the conformation of acylated collagen, which might be concluded that the hydrophobic interaction improved the thermostability of collagen. - Highlights: • Acylated collagen retained the unique triple helix conformation. • Acylated collagen had stronger thermostability than native collagen. • Amide I was the most sensitive band to the temperature for acylated collagen. • Amide II was the most sensitive band to the temperature for native collagen. • Auto-peak at 1680 cm −1 for acylated collagen disappeared at higher temperature

  5. Total synthesis of fluoxetine and duloxetine through an in situ imine formation/borylation/transimination and reduction approach.

    Calow, Adam D J; Fernández, Elena; Whiting, Andrew

    2014-08-28

    We report efficient, catalytic, asymmetric total syntheses of both (R)-fluoxetine and (S)-duloxetine from α,β-unsaturated aldehydes conducting five sequential one-pot steps (imine formation/copper mediated β-borylation/transimination/reduction/oxidation) followed by the specific ether group formation which deliver the desired products (R)-fluoxetine in 45% yield (96% ee) and (S)-duloxetine in 47% yield (94% ee).

  6. Convergent Synthesis of Piperidines by the Union of Conjugated Alkynes with Imines: A Unique Regioselective Bond Construction for Heterocycle Synthesis

    Chen, Ming Z.; Micalizio, Glenn C.

    2009-01-01

    A two-step process is described for the union of aromatic imines, conjugated alkynes and aldehydes that results in a stereoselective synthesis of highly substituted piperidines. This synthetic process has been made possible by defining a unique regioselective functionalization of conjugated alkynes that establishes a suitably functionalized substrate for subsequent heterocycle-forming cationic annulation. Given the flexibility of the coupling process, heterocycles can be accessed through a process that establishes up to four stereogenic centers and four fused rings. PMID:19817447

  7. Highly efficient oxidation of amines to imines by singlet oxygen and its application in Ugi-type reactions.

    Jiang, Gaoxi; Chen, Jian; Huang, Jie-Sheng; Che, Chi-Ming

    2009-10-15

    A variety of secondary benzylic amines were oxidized to imines in 90% to >99% yields by singlet oxygen generated from oxygen and a porphyrin photosensitizer. On the basis of these reactions, a protocol was developed for oxidative Ugi-type reactions with singlet oxygen as the oxidant. This protocol has been used to synthesize C1- and N-functionalized benzylic amines in up to 96% yields.

  8. Enzymatic production of biodiesel from microalgal oil using ethyl acetate as an acyl acceptor.

    Alavijeh, Razieh Shafiee; Tabandeh, Fatemeh; Tavakoli, Omid; Karkhane, Aliasghar; Shariati, Parvin

    2015-01-01

    Microalgae have become an important source of biomass for biodiesel production. In enzymatic transesterification reaction, the enzyme activity is decreased in presence of alcohols. The use of different acyl acceptors such as methyl/ethyl acetate is suggested as an alternative and effective way to overcome this problem. In this study, ethyl acetate was used for the first time in the enzymatic production of biodiesel by using microalga, Chlorella vulgaris, as a triglyceride source. Enzymatic conversion of such fatty acids to biodiesel was catalyzed by Novozym 435 as an efficient immobilized lipase which is extensively used in biodiesel production. The best conversion yield of 66.71% was obtained at the ethyl acetate to oil molar ratio of 13:1 and Novozym 435 concentration of 40%, based on the amount of oil, and a time period of 72 h at 40℃. The results showed that ethyl acetate have no adverse effect on lipase activity and the biodiesel amount was not decreased even after seven transesterification cycles, so ethyl acetate has a great potential to be substituted for short-chain alcohols in transesterification reaction.

  9. Medium-chain acyl-CoA dehydrogenase deficiency

    Waddell, Leigh; Wiley, Veronica; Carpenter, Kevin

    2006-01-01

    The fatty acid oxidation disorder most commonly identified by tandem mass spectrometry newborn screening is the potentially fatal medium-chain acyl-CoA dehydrogenase deficiency (MCAD). In clinically presenting cases, 80% are homozygous for the common mutation, c.985A > G and 18% heterozygous. We ...

  10. Antileishmanial Activity of Aldonamides and N-Acyl-Diamine Derivatives

    Elaine S. Coimbra

    2008-01-01

    Full Text Available A number of lipophilic N-acyl-diamines and aldonamides have been synthesized and tested for their in vitro antiproliferative activity against Leishmania amazonensis and L. chagasi. Ribonamides, having one amino group, displayed good to moderate inhibition of parasite growth. The best result was obtained for compounds 10 and 15 with IC50 against L. chagasi below 5 μM.

  11. Rapid Hydrogen Shift Reactions in Acyl Peroxy Radicals

    Knap, Hasse Christian; Jørgensen, Solvejg

    2017-01-01

    -shift with X = 6, 7, 8, or 9) in the hydroperoxy acyl peroxy radicals, this H-shift is a reversible reaction and it scrambles between two peroxides, hydroperoxy acyl peroxy and peroxy peroxoic acid radicals. The forward reaction rate constants of the 1,X-OOH H-shift reactions are estimated to be above 103 s–1...... with transition state theory corrected with Eckart quantum tunnelling correction. The ratio between the forward and reverse reaction rate constant of the 1,X-OOH H-shift reactions is around ∼105. Therefore, the equilibrium is pushed toward the production of peroxy peroxoic acid radicals. These very fast 1,X-OOH H......We have used quantum mechanical chemical calculations (CCSD(T)-F12a/cc-pVDZ-F12//M06-2X/aug-cc-pVTZ) to investigate the hydrogen shift (H-shift) reactions in acyl peroxy and hydroperoxy acyl peroxy radicals. We have focused on the H-shift reactions from a hydroperoxy group (OOH) (1,X-OOH H...

  12. Imaging N-acyl homoserine lactone quorum sensing in vivo

    Christensen, Louise Dahl; van Gennip, Maria; Jakobsen, Tim Holm

    2011-01-01

    In order to study N-acyl homoserine lactone (AHL)-based quorum sensing in vivo, we present a protocol using an Escherichia coli strain equipped with a luxR-based monitor system, which in the presence of exogenous AHL molecules expresses a green fluorescent protein (GFP). Lungs from mice challenged...

  13. Imaging N-acyl homoserine lactone quorum sensing in vivo

    Hultqvist, Louise Dahl; Alhede, Maria; Jakobsen, Tim Holm

    2018-01-01

    In order to study N-acyl homoserine lactone (AHL)-based quorum sensing in vivo, we present a protocol using an Escherichia coli strain equipped with a luxR-based monitor system, which in the presence of exogenous AHL molecules expresses a green fluorescent protein (GFP). Lungs from mice challenged...

  14. The Acylation State of Surface Lipoproteins of Mollicute Acholeplasma laidlawii*

    Serebryakova, Marina V.; Demina, Irina A.; Galyamina, Maria A.; Kondratov, Ilya G.; Ladygina, Valentina G.; Govorun, Vadim M.

    2011-01-01

    Acylation of the N-terminal Cys residue is an essential, ubiquitous, and uniquely bacterial posttranslational modification that allows anchoring of proteins to the lipid membrane. In Gram-negative bacteria, acylation proceeds through three sequential steps requiring lipoprotein diacylglyceryltransferase, lipoprotein signal peptidase, and finally lipoprotein N-acyltransferase. The apparent lack of genes coding for recognizable homologs of lipoprotein N-acyltransferase in Gram-positive bacteria and Mollicutes suggests that the final step of the protein acylation process may be absent in these organisms. In this work, we monitored the acylation state of eight major lipoproteins of the mollicute Acholeplasma laidlawii using a combination of standard two-dimensional gel electrophoresis protein separation, blotting to nitrocellulose membranes, and MALDI-MS identification of modified N-terminal tryptic peptides. We show that for each A. laidlawii lipoprotein studied a third fatty acid in an amide linkage on the N-terminal Cys residue is present, whereas diacylated species were not detected. The result thus proves that A. laidlawii encodes a lipoprotein N-acyltransferase activity. We hypothesize that N-acyltransferases encoded by genes non-homologous to N-acyltransferases of Gram-negative bacteria are also present in other mollicutes and Gram-positive bacteria. PMID:21540185

  15. Catalytic α-arylation of imines leading to N-unprotected indoles and azaindoles

    Marelli, Enrico

    2016-03-30

    A Palladium-N-heterocyclic carbene-catalyzed methodology for the synthesis of substituted, N-unprotected indoles and azaindoles is reported. The protocol permits access to various, highly substituted members of these classes of compounds. Although two possible reactions pathways (deprotonative and Heck-like) can be proposed, control experiments, supported by computational studies, point towards a deprotonative mechanism being operative.

  16. Catalytic α-arylation of imines leading to N-unprotected indoles and azaindoles

    Marelli, Enrico; Corpet, Martin; Minenkov, Yury; Neyyappadath, Rifahath; Bismuto, Alessandro; Buccolini, Giulia; Curcio, Massimiliano; Cavallo, Luigi; Nolan, Steven P.

    2016-01-01

    A Palladium-N-heterocyclic carbene-catalyzed methodology for the synthesis of substituted, N-unprotected indoles and azaindoles is reported. The protocol permits access to various, highly substituted members of these classes of compounds. Although two possible reactions pathways (deprotonative and Heck-like) can be proposed, control experiments, supported by computational studies, point towards a deprotonative mechanism being operative.

  17. Clarification on the decarboxylation mechanism in KasA based on the protonation state of key residues in the acyl-enzyme state.

    Lee, Wook; Engels, Bernd

    2013-07-11

    The β-ketoacyl ACP synthase I (KasA) is a promising drug target because it is essential for the survival of Mycobacterium tuberculosis , a causative agent of tuberculosis. It catalyzes a condensation reaction that comprises three steps. The resulting elongated acyl chains are subsequently needed for the cell wall construction. While the mechanism of the first step (acylation of Cys171 in the active site) is straightforward already, the second step (decarboxylation of malonyl substrate) has been controversial due to the difficulty in determining the correct protonation states of the involved residues (His311, His345, Lys340, Glu354). Available experimental data suggest three possible mechanisms which differ considerably. They are not consistent with each other because these studies could not be performed for KasA at the beginning of decarboxylation step (acyl-enzyme state of KasA). Instead, different mutants had to be used which are expected to resemble this situation. In this first computational study about this topic, we use the free energy perturbation (FEP) method to compute the relevant pKa values in the acyl-enzyme state of KasA and use molecular dynamics (MD) simulations to rationalize the results. Subsequent density functional theory (DFT)-based quantum mechanical/molecular mechanical (QM/MM) MD simulations and umbrella samplings have been used to disentangle the close relationships between the protonation states of the involved residues. By these simulations, we can address the preferred protonation states and roles of the residues involved in decarboxylation reaction, thereby suggesting the possible mechanism for the decarboxylation step.

  18. Graphite-supported gold nanoparticles as efficient catalyst for aerobic oxidation of benzylic amines to imines and N-substituted 1,2,3,4-tetrahydroisoquinolines to amides: synthetic applications and mechanistic study.

    So, Man-Ho; Liu, Yungen; Ho, Chi-Ming; Che, Chi-Ming

    2009-10-05

    Selective oxidation of amines using oxygen as terminal oxidant is an important area in green chemistry. In this work, we describe the use of graphite-supported gold nanoparticles (AuNPs/C) to catalyze aerobic oxidation of cyclic and acyclic benzylic amines to the corresponding imines with moderate-to-excellent substrate conversions (43-100%) and product yields (66-99%) (19 examples). Oxidation of N-substituted 1,2,3,4-tetrahydroisoquinolines in the presence of aqueous NaHCO3 solution gave the corresponding amides in good yields (83-93%) with high selectivity (up to amide/enamide=93:4) (6 examples). The same protocol can be applied to the synthesis of benzimidazoles from the reaction of o-phenylenediamines with benzaldehydes under aerobic conditions (8 examples). By simple centrifugation, AuNPs/C can be recovered and reused for ten consecutive runs for the oxidation of dibenzylamine to N-benzylidene(phenyl)methanamine without significant loss of catalytic activity and selectivity. This protocol "AuNPs/C+O2" can be scaled to the gram scale, and 8.9 g (84 % isolated yield) of 3,4-dihydroisoquinoline can be obtained from the oxidation of 10 g 1,2,3,4-tetrahydroisoquinoline in a one-pot reaction. Based on the results of kinetic studies, radical traps experiment, and Hammett plot, a mechanism involving the hydrogen-transfer reaction from amine to metal and oxidation of M-H is proposed.

  19. Striving towards improved Friedel-Crafts acylation catalysts

    Scott, N.M.; Deacon, G.B.

    1998-01-01

    Full text: Lanthanum, ytterbium and scandium salts of trifluoromethanesulfonic acid have been shown to act as promising Lewis acid catalysts for the Friedel-Craft acylation reactions. In our study catalytic acylation of anisole by acetic anhydride in nitroethane was investigated. Yields were determined after extraction of para-methoxyacetophenone from the reaction mixture by G.L.C using the external standardisation method. Anhydrous lanthanoid tris-triflate salts [Ln(O 3 SCF 3 ) 3 , Ln La, Y, Nd, Eu and Yb] were initially investigated as catalysts. Ytterbium tris-triflate was found to be the most effective giving ∼90% of the acylation product. The hydrated lanthanide tris-nitrate salts [Ln(NO 3 ) 3 .nH 2 O, Ln = La, Nd, Eu and Yb] were also investigated using in situ dehydration with acetic anhydride. These were found to have low solubility in the reaction mixture and gave poor yields of para-methoxyacetophenone. The formation of side products was suggested by the low total recovery of anisole and para-methoxyacetophenone. The blocking of coordination sites of these catalysts by tetraglyme resulted in a 50% reduction in acylation activity compared with the simple salt. Addition of Li(O 3 SCF 3 ) to Ln(O 3 SCF 3 ) 3 catalysts (ratio of 4:1)had only a slight accelerating effect on the Friedel-Crafts acylation reaction and the yield was only marginally greater than that in the absence of the added salt. In contrast Li(ClO 4 ) dramatically decreased reaction times and improved the yield of para-methoxyace-tophenone, as recently reported

  20. Mesomorphic Behavior of Symmetrical and Unsymmetrical Azomethines with Two Imine Groups

    Patrice Rannou

    2009-02-01

    Full Text Available Seven symmetrical azomethines with two imine groups (HC=N were synthesized by condensation of the benzene-1,4-dicarboxaldehydewith five amines (first group: A1-A5 and of the 2,5-thiophenedicarboxaldehyde with two amines (second group: AT1-AT2. Additionally, two unsymmetrical azomethines were obtained by a two step condensation of benzene-1,4-dicarboxaldehydewith pyren-1-amine(1st step (abbreviated hereinafter as AP1 and then AP1 was reacted with4-dodecylaniline or 4-hexadecylaniline (2nd step (third group: AP1A-AP1B. Liquid crystalline properties of the azomethines were studied by differential scanning calorimetry (DSC, polarizing optical microscopy (POM and UV-vis spectroscopy in the function of temperature [UV-vis(T]. The Wide-Angle X-ray Diffraction (WAXD technique was used to probe the structural properties of the azomethines. Mesomorphic behavior was observed for symmetrical and unsymmetrical azomethines, obtained from the benzene-1,4-dicarboxaldehyde and symmetrical ones prepared from 2,5-thiophenedicarboxaldehyde and different amineshaving aliphatic chains. Based on the POM and DSC measurements the following mesophases were detected: nematic, smectic A, smectic C, smectic F (I, smectic G (J.

  1. Synthesis of Chromane Derivatives via Indium-mediated Intramolecular Allenylation and Allylation to Imines

    Kang, Han Young; Yu, Yeon Kwon

    2004-01-01

    The results of preparing chromans by intramolecular allylation are shown in Table 2. The results indicated that the indium-mediated allylation was not as efficient as the allenylation. About 10-20% decrease in yields was observed. As mentioned above, in each case only a single isomer was observed, and the stereochemistry of the product was determined as cis by analysis of 1 H NMR and NOE spectra. There are, however, still some limitations in these transformations. Especially, in the case of allylation mixtures of cis and trans isomers are always produced in about 2 : 1 ratio (cis/trans). The ratio was not improved under the various reaction conditions we attempted. Since the indium-mediated addition to carbonyl groups has been successful, it occurred to us that it would be worthwhile to test the addition to carbon-nitrogen double bonds, that is, imine groups. We wish to report here the results of the investigations on allylation and allenylation to C=N bond to provide the chromane structures. The whole transformations

  2. On the mechanism of imine elimination from Fischer tungsten carbene complexes

    Philipp Veit

    2016-06-01

    Full Text Available (Aminoferrocenyl(ferrocenylcarbene(pentacarbonyltungsten(0 (CO5W=C(NHFcFc (W(CO5(E-2 is synthesized by nucleophilic substitution of the ethoxy group of (CO5W=C(OEtFc (M(CO5(1Et by ferrocenyl amide Fc-NH– (Fc = ferrocenyl. W(CO5(E-2 thermally and photochemically eliminates bulky E-1,2-diferrocenylimine (E-3 via a formal 1,2-H shift from the N to the carbene C atom. Kinetic and mechanistic studies to the formation of imine E-3 are performed by NMR, IR and UV–vis spectroscopy and liquid injection field desorption ionization (LIFDI mass spectrometry as well as by trapping experiments for low-coordinate tungsten complexes with triphenylphosphane. W(CO5(E-2 decays thermally in a first-order rate-law with a Gibbs free energy of activation of ΔG‡298K = 112 kJ mol−1. Three proposed mechanistic pathways are taken into account and supported by detailed (time-dependent densitiy functional theory [(TD-DFT] calculations. The preferred pathway is initiated by an irreversible CO dissociation, followed by an oxidative addition/pseudorotation/reductive elimination pathway with short-lived, elusive seven-coordinate hydrido tungsten(II intermediates cis(N,H-W(CO4(H(Z-15 and cis(C,H-W(CO4(H(Z-15.

  3. d-Fructose-Decorated Poly(ethylene imine) for Human Breast Cancer Cell Targeting.

    Englert, Christoph; Pröhl, Michael; Czaplewska, Justyna A; Fritzsche, Carolin; Preußger, Elisabeth; Schubert, Ulrich S; Traeger, Anja; Gottschaldt, Michael

    2017-08-01

    The high affinity of GLUT5 transporter for d-fructose in breast cancer cells has been discussed intensely. In this contribution, high molar mass linear poly(ethylene imine) (LPEI) is functionalized with d-fructose moieties to combine the selectivity for the GLUT5 transporter with the delivery potential of PEI for genetic material. The four-step synthesis of a thiol-group bearing d-fructose enables the decoration of a cationic polymer backbone with d-fructose via thiol-ene photoaddition. The functionalization of LPEI is confirmed by 2D NMR techniques, elemental analysis, and size exclusion chromatography. Importantly, a d-fructose decoration of 16% renders the polymers water-soluble and eliminates the cytotoxicity of PEI in noncancer L929 cells, accompanied by a reduced unspecific cellular uptake of the genetic material. In contrast, the cytotoxicity as well as the cell specific uptake is increased for triple negative MDA-MB-231 breast cancer cells. Therefore, the introduction of d-fructose shows superior potential for cell targeting, which can be assumed to be GLUT5 dependent. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Syntheses of poly(phenoxy-imine)s anchored with carboxyl group: Characterization and photovoltaic studies

    Kaya, İsmet; Ayten, Bahar; Şenol, Dilek

    2018-04-01

    A serious of pyridine based Schiff bases (M1, M2, and M3) were synthesized via condensation reaction of 4-aminosalicyclic acid with 2-pyridinecarboxaldehyde, 3-pyridine carboxyaldehyde and 4-pyridinecarboxaldehyde, respectively. The transformation of Schiff bases into their poly(phenoxy-imine) species (P1, P2, P3) was obtained using oxidative polycondensation (OP) by NaOCl as the oxidant in alkaline medium at 70 °C. The structures of the synthesized compounds were characterized by solubility test, FT-IR, UV-Vis and NMR techniques. Thermal data were obtained by TG-DTA and DSC techniques. Photoluminescence (PL) properties of the synthesized materials were examined in organic solvent. Fluorescence measurements were carried out in various concentrated solutions to determine the optimum concentrations and PL intensities. P3 could be used in light-emitting diodes due to its multicolor (white, blue, green and yellow) light-emitting property. The efficiency (η) of a solar cell of P1, P2 and P3 were determined by single channel Potentiostat/Galvanostat with electrochemical impedance spectroscopy. The order of conductivities was found to be as P3>P2>P1 as a result of iodine doping. The best performing photovoltaic cell with Isc (mA cm-2), Voc (V), FF, and η (%) as -0.642, 0.399, 0.461 and -0.118 was obtained for P3.

  5. Activation of Exogenous Fatty Acids to Acyl-Acyl Carrier Protein Cannot Bypass FabI Inhibition in Neisseria*

    Yao, Jiangwei; Bruhn, David F.; Frank, Matthew W.; Lee, Richard E.; Rock, Charles O.

    2016-01-01

    Neisseria is a Gram-negative pathogen with phospholipids composed of straight chain saturated and monounsaturated fatty acids, the ability to incorporate exogenous fatty acids, and lipopolysaccharides that are not essential. The FabI inhibitor, AFN-1252, was deployed as a chemical biology tool to determine whether Neisseria can bypass the inhibition of fatty acid synthesis by incorporating exogenous fatty acids. Neisseria encodes a functional FabI that was potently inhibited by AFN-1252. AFN-1252 caused a dose-dependent inhibition of fatty acid synthesis in growing Neisseria, a delayed inhibition of growth phenotype, and minimal inhibition of DNA, RNA, and protein synthesis, showing that its mode of action is through inhibiting fatty acid synthesis. Isotopic fatty acid labeling experiments showed that Neisseria encodes the ability to incorporate exogenous fatty acids into its phospholipids by an acyl-acyl carrier protein-dependent pathway. However, AFN-1252 remained an effective antibacterial when Neisseria were supplemented with exogenous fatty acids. These results demonstrate that extracellular fatty acids are activated by an acyl-acyl carrier protein synthetase (AasN) and validate type II fatty acid synthesis (FabI) as a therapeutic target against Neisseria. PMID:26567338

  6. Role of acylCoA binding protein in acylCoA transport, metabolism and cell signaling

    Knudsen, J; Jensen, M V; Hansen, J K

    1999-01-01

    and pool formation and therefore also for the function of LCAs as metabolites and regulators of cellular functions [1]. The major factors controlling the free concentration of cytosol long chain acylCoA ester (LCA) include ACBP [2], sterol carrier protein 2 (SCP2) [3] and fatty acid binding protein (FABP...

  7. Flavin-catalyzed redox tailoring reactions in natural product biosynthesis.

    Teufel, Robin

    2017-10-15

    Natural products are distinct and often highly complex organic molecules that constitute not only an important drug source, but have also pushed the field of organic chemistry by providing intricate targets for total synthesis. How the astonishing structural diversity of natural products is enzymatically generated in biosynthetic pathways remains a challenging research area, which requires detailed and sophisticated approaches to elucidate the underlying catalytic mechanisms. Commonly, the diversification of precursor molecules into distinct natural products relies on the action of pathway-specific tailoring enzymes that catalyze, e.g., acylations, glycosylations, or redox reactions. This review highlights a selection of tailoring enzymes that employ riboflavin (vitamin B2)-derived cofactors (FAD and FMN) to facilitate unusual redox catalysis and steer the formation of complex natural product pharmacophores. Remarkably, several such recently reported flavin-dependent tailoring enzymes expand the classical paradigms of flavin biochemistry leading, e.g., to the discovery of the flavin-N5-oxide - a novel flavin redox state and oxygenating species. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Xanthomonas campestris RpfB is a Fatty Acyl-CoA Ligase Required to Counteract the Thioesterase Activity of the RpfF Diffusible Signal Factor (DSF) Synthase

    Bi, Hongkai; Yu, Yonghong; Dong, Huijuan; Wang, Haihong; Cronan, John E.

    2014-01-01

    SUMMARY In Xanthomonas campestris pv. campestris (Xcc), the proteins encoded by the rpf (regulator of pathogenicity factor) gene cluster produce and sense a fatty acid signal molecule called diffusible signaling factor (DSF, 2(Z)-11-methyldodecenoic acid). RpfB was reported to be involved in DSF processing and was predicted to encode an acyl-CoA ligase. We report that RpfB activates a wide range of fatty acids to their CoA esters in vitro. Moreover, RpfB can functionally replace the paradigm bacterial acyl-CoA ligase, Escherichia coli FadD, in the E. coli β-oxidation pathway and deletion of RpfB from the Xcc genome results in a strain unable to utilize fatty acids as carbon sources. An essential RpfB function in the pathogenicity factor pathway was demonstrated by the properties of a strain deleted for both the rpfB and rpfC genes. The ΔrpfB ΔrpfC strain grew poorly and lysed upon entering stationary phase. Deletion of rpfF, the gene encoding the DSF synthetic enzyme, restored normal growth to this strain. RpfF is a dual function enzyme that synthesizes DSF by dehydration of a 3-hydroxyacyl-acyl carrier protein (ACP) fatty acid synthetic intermediate and also cleaves the thioester bond linking DSF to ACP. However, the RpfF thioesterase activity is of broad specificity and upon elimination of its RpfC inhibitor RpfF attains maximal activity and its thioesterase activity proceeds to block membrane lipid synthesis by cleavage of acyl-ACP intermediates. This resulted in release of the nascent acyl chains to the medium as free fatty acids. This lack of acyl chains for phospholipid synthesis results in cell lysis unless RpfB is present to counteract the RpfF thioesterase activity by catalyzing uptake and activation of the free fatty acids to give acyl-CoAs that can be utilized to restore membrane lipid synthesis. Heterologous expression of a different fatty acid activating enzyme, the Vibrio harveyi acyl-ACP synthetase, replaced RpfB in counteracting the effects of

  9. Arabidopsis and Maize RidA Proteins Preempt Reactive Enamine/Imine Damage to Branched-Chain Amino Acid Biosynthesis in Plastids[C][W][OPEN

    Niehaus, Thomas D.; Nguyen, Thuy N.D.; Gidda, Satinder K.; ElBadawi-Sidhu, Mona; Lambrecht, Jennifer A.; McCarty, Donald R.; Downs, Diana M.; Cooper, Arthur J.L.; Fiehn, Oliver; Mullen, Robert T.; Hanson, Andrew D.

    2014-01-01

    RidA (for Reactive Intermediate Deaminase A) proteins are ubiquitous, yet their function in eukaryotes is unclear. It is known that deleting Salmonella enterica ridA causes Ser sensitivity and that S. enterica RidA and its homologs from other organisms hydrolyze the enamine/imine intermediates that Thr dehydratase forms from Ser or Thr. In S. enterica, the Ser-derived enamine/imine inactivates a branched-chain aminotransferase; RidA prevents this damage. Arabidopsis thaliana and maize (Zea mays) have a RidA homolog that is predicted to be plastidial. Expression of either homolog complemented the Ser sensitivity of the S. enterica ridA mutant. The purified proteins hydrolyzed the enamines/imines formed by Thr dehydratase from Ser or Thr and protected the Arabidopsis plastidial branched-chain aminotransferase BCAT3 from inactivation by the Ser-derived enamine/imine. In vitro chloroplast import assays and in vivo localization of green fluorescent protein fusions showed that Arabidopsis RidA and Thr dehydratase are chloroplast targeted. Disrupting Arabidopsis RidA reduced root growth and raised the root and shoot levels of the branched-chain amino acid biosynthesis intermediate 2-oxobutanoate; Ser treatment exacerbated these effects in roots. Supplying Ile reversed the root growth defect. These results indicate that plastidial RidA proteins can preempt damage to BCAT3 and Ile biosynthesis by hydrolyzing the Ser-derived enamine/imine product of Thr dehydratase. PMID:25070638

  10. Thermodynamics of Enzyme-Catalyzed Reactions Database

    SRD 74 Thermodynamics of Enzyme-Catalyzed Reactions Database (Web, free access)   The Thermodynamics of Enzyme-Catalyzed Reactions Database contains thermodynamic data on enzyme-catalyzed reactions that have been recently published in the Journal of Physical and Chemical Reference Data (JPCRD). For each reaction the following information is provided: the reference for the data, the reaction studied, the name of the enzyme used and its Enzyme Commission number, the method of measurement, the data and an evaluation thereof.

  11. IMMOBILIZATION OF TANNIN ACYL HYDROLASE FROM ASPERGILLUS NIGER

    B. Lenin Kumar*, N. Lokeswari and D. Sriramireddy

    2013-01-01

    ABSTRACT: Tannin acyl hydrolase, commonly referred to as tannase (E.C. 3.1.1.20), an inducible extra-cellular enzyme produced by a number of animals, plants and microbes. In this investigation, tannase production under solid-state fermentation by using Aspergillus niger and the waste residue of cashew husk was used as substrate for obtaining the desired fermented product. Microbial tannase is more stable than tannase from other sources like plants or animals. Tannase from fungal sources are r...

  12. Defluoridation potential of jute fibers grafted with fatty acyl chain

    Manna, Suvendu; Saha, Prosenjit [Materials Science Centre, IIT Kharagpur, WB 721302 (India); Roy, Debasis, E-mail: debasis@civil.iitkgp.ernet.in [Department of Civil Engineering, IIT Kharagpur, WB 721302 (India); Sen, Ramkrishna [Department of Biotechnology, IIT Kharagpur, WB 721302 (India); Adhikari, Basudam [Materials Science Centre, IIT Kharagpur, WB 721302 (India)

    2015-11-30

    Graphical abstract: - Highlights: • Acyl chain grafted jute has been shown to accumulate fluoride ions. • Covalent and hydrogen bonding and protonation were the contributing factors. • The process is relatively inexpensive and maintenance-free. • Acyl chain grafted jute showed higher fluoride ions accumulation than alternatives. - Abstract: Waterborne fluoride is usually removed from water by coagulation, adsorption, ion exchange, electro dialysis or reverse osmosis. These processes are often effective over narrow pH ranges, release ions considered hazardous to human health or produce large volumes of toxic sludge that are difficult to handle and dispose. Although plant matters have been shown to remove waterborne fluoride, they suffer from poor removal efficiency. Following from the insight that interaction between microbial carbohydrate biopolymers and anionic surfaces is often facilitated by lipids, an attempt has been made to enhance fluoride adsorption efficiency of jute by grafting the lignocellulosic fiber with fatty acyl chains found in vegetable oils. Fluoride removal efficiency of grafted jute was found to be comparable or higher than those of alternative defluoridation processes. Infrared and X-ray photoelectron spectroscopic evidence indicated that hydrogen bonding, protonation and C−F bonding were responsible for fluoride accumulation on grafted jute. Adsorption based on grafted jute fibers appears to be an economical, sustainable and eco-friendly alternative technique for removing waterborne fluoride.

  13. Turnover and metabolism of phosphatidylglycerol acyl moieties in E. coli

    Cooper, C.L.; Rock, C.O.

    1987-01-01

    Fatty acids synthesized in mutants (plsB) blocked in de novo phospholipid biosynthesis were preferentially transferred to phosphatidylglycerol (PtdGro). The ratio of phospholipid species labeled with 32 P and [ 3 H]acetate in the absence of glycerol-3-P acyltransferase activity indicated that [ 3 H]acetate incorporation into PtdGro was due to fatty acid turnover. The magnitude of the turnover process was difficult to estimate due to a significant contraction of the acetyl-CoA pool following the inhibition of phospholipid synthesis. A possible connection between PtdGro turnover and protein acylation was investigated in an E. coli strain containing a lipoprotein expression vector. Cells were prelabeled with [ 3 H]acetate and lipoprotein expression was induced concomitant with the addition of exogenous [ 14 C]-palmitate. [ 14 C] Palmitate was assimilated into the l-position of phosphatidylethanolamine and transferred to the amino terminus of the lipoprotein. In contrast, the ester-linked lipoprotein fatty acids and PtdGro were not enriched in carbon-14 implying a metabolic relationship between these two pools. The data suggest that turnover of PtdGro acyl moieties is related to protein acylation, but a direct link between the two processes remains to be established

  14. Intracellular siRNA delivery dynamics of integrin-targeted, PEGylated chitosan-poly(ethylene imine) hybrid nanoparticles

    Ragelle, Héloïse; Colombo, Stefano; Pourcelle, Vincent

    2015-01-01

    chitosan-poly(ethylene imine) hybrid nanoparticles. The amount of intracellular siRNA delivered by αvβ3-targeted versus non-targeted nanoparticles was quantified in the human non-small cell lung carcinoma cell line H1299 expressing enhanced green fluorescent protein (EGFP) using a stem-loop reverse...... that these nanoparticles might end up in late endosomes or lysosomes without releasing their cargo to the cell cytoplasm. Thus, the silencing efficiency of the chitosan-based nanoparticles is strongly dependent on the uptake and the intracellular trafficking in H1299 EGFP cells, which is critical information towards...

  15. A Mononuclear Iron-Dependent Methyltransferase Catalyzes Initial Steps in Assembly of the Apratoxin A Polyketide Starter Unit.

    Skiba, Meredith A; Sikkema, Andrew P; Moss, Nathan A; Tran, Collin L; Sturgis, Rebecca M; Gerwick, Lena; Gerwick, William H; Sherman, David H; Smith, Janet L

    2017-12-15

    Natural product biosynthetic pathways contain a plethora of enzymatic tools to carry out difficult biosynthetic transformations. Here, we discover an unusual mononuclear iron-dependent methyltransferase that acts in the initiation steps of apratoxin A biosynthesis (AprA MT1). Fe 3+ -replete AprA MT1 catalyzes one or two methyl transfer reactions on the substrate malonyl-ACP (acyl carrier protein), whereas Co 2+ , Fe 2+ , Mn 2+ , and Ni 2+ support only a single methyl transfer. MT1 homologues exist within the "GNAT" (GCN5-related N-acetyltransferase) loading modules of several modular biosynthetic pathways with propionyl, isobutyryl, or pivaloyl starter units. GNAT domains are thought to catalyze decarboxylation of malonyl-CoA and acetyl transfer to a carrier protein. In AprA, the GNAT domain lacks both decarboxylation and acyl transfer activity. A crystal structure of the AprA MT1-GNAT di-domain with bound Mn 2+ , malonate, and the methyl donor S-adenosylmethionine (SAM) reveals that the malonyl substrate is a bidentate metal ligand, indicating that the metal acts as a Lewis acid to promote methylation of the malonyl α-carbon. The GNAT domain is truncated relative to functional homologues. These results afford an expanded understanding of MT1-GNAT structure and activity and permit the functional annotation of homologous GNAT loading modules both with and without methyltransferases, additionally revealing their rapid evolutionary adaptation in different biosynthetic contexts.

  16. The R117A variant of the Escherichia coli transacylase FabD synthesizes novel acyl-(acyl carrier proteins).

    Marcella, Aaron M; Barb, Adam W

    2017-12-01

    The commercial impact of fermentation systems producing novel and biorenewable chemicals will flourish with the expansion of enzymes engineered to synthesize new molecules. Though a small degree of natural variability exists in fatty acid biosynthesis, the molecular space accessible through enzyme engineering is fundamentally limitless. Prokaryotic fatty acid biosynthesis enzymes build carbon chains on a functionalized acyl carrier protein (ACP) that provides solubility, stability, and a scaffold for interactions with the synthetic enzymes. Here, we identify the malonyl-coenzyme A (CoA)/holo-ACP transacylase (FabD) from Escherichia coli as a platform enzyme for engineering to diversify microbial fatty acid biosynthesis. The FabD R117A variant produced novel ACP-based primer and extender units for fatty acid biosynthesis. Unlike the wild-type enzyme that is highly specific for malonyl-CoA to produce malonyl-ACP, the R117A variant synthesized acetyl-ACP, succinyl-ACP, isobutyryl-ACP, 2-butenoyl-ACP, and β-hydroxybutyryl-ACP among others from holo-ACP and the corresponding acyl-CoAs with specific activities from 3.7 to 120 nmol min -1  mg -1 . FabD R117A maintained K M values for holo-ACP (~ 40 μM) and displayed small changes in K M for acetoacetyl-CoA (110 ± 30 μM) and acetyl-CoA (200 ± 70 μM) when compared to malonyl-CoA (80 ± 30 μM). FabD R117A represents a novel catalyst that synthesizes a broad range of acyl-acyl-ACPs.

  17. Rivastigmine Improves Appetite by Increasing the Plasma Acyl/Des-Acyl Ghrelin Ratio and Cortisol in Alzheimer Disease

    Yoshiko Furiya

    2018-03-01

    Full Text Available Background: Weight loss accelerates cognitive decline and increases mortality in patients with dementia. While acetylcholinesterase (AChE inhibitors are known to cause appetite loss, we sometimes encounter patients in whom switching from donepezil (AChE inhibitor to rivastigmine (AChE and butyrylcholinesterase [BuChE] inhibitor improves appetite. Since BuChE inactivates ghrelin, a potent orexigenic hormone, we speculated that rivastigmine improves appetite by inhibiting BuChE-mediated ghrelin inactivation. Methods: The subjects were patients with mild to moderate Alzheimer disease treated with either rivastigmine patch (n = 11 or donepezil (n = 11 for 6 months. Before and after treatment, we evaluated appetite (0, decreased; 1, slightly decreased; 2, normal; 3, slightly increased; 4, increased, cognitive function, and blood biochemical variables, including various hormones. Results: Rivastigmine treatment significantly improved appetite (from 1.6 ± 0.5 to 2.6 ± 0.7, whereas donepezil treatment did not (from 2.0 ± 0.0 to 1.8 ± 0.4. Simultaneously, rivastigmine, but not donepezil, significantly decreased the serum cholinesterase activity (from 304.3 ± 60.5 to 246.8 ± 78.5 IU/L and increased the cortisol level (from 11.86 ± 3.12 to 14.61 ± 3.29 μg/dL and the acyl/des-acyl ghrelin ratio (from 4.03 ± 2.96 to 5.28 ± 2.72. The levels of leptin, insulin, total ghrel­in, and cognitive function were not significantly affected by either treatment. Conclusions: Our results suggest that compared with donepezil, rivastigmine has the advantage of improving appetite by increasing the acyl/des-acyl ghrelin ratio and cortisol level, thereby preventing weight loss.

  18. Characterization of Lipid A Variants by Energy-Resolved Mass Spectrometry: Impact of Acyl Chains

    Crittenden, Christopher M.; Akin, Lucas D.; Morrison, Lindsay J.; Trent, M. Stephen; Brodbelt, Jennifer S.

    2017-06-01

    Lipid A molecules consist of a diglucosamine sugar core with a number of appended acyl chains that vary in their length and connectivity. Because of the challenging nature of characterizing these molecules and differentiating between isomeric species, an energy-resolved MS/MS strategy was undertaken to track the fragmentation trends and map genealogies of product ions originating from consecutive cleavages of acyl chains. Generalizations were developed based on the number and locations of the primary and secondary acyl chains as well as variations in preferential cleavages arising from the location of the phosphate groups. Secondary acyl chain cleavage occurs most readily for lipid A species at the 3' position, followed by primary acyl chain fragmentation at both the 3' and 3 positions. In the instances of bisphosphorylated lipid A variants, phosphate loss occurs readily in conjunction with the most favorable primary and secondary acyl chain cleavages. [Figure not available: see fulltext.

  19. Phospholipase D catalyzes phospholipid metabolism in chemotactic peptide-stimulated HL-60 granulocytes

    Pai, J.K.; Siegel, M.I.; Egan, R.W.; Billah, M.M.

    1988-01-01

    There exists circumstantial evidence for activation of phospholipase D (PLD) in intact cells. However, because of the complexity of phospholipid remodeling processes, it is essential to distinguish PLD clearly from other phospholipases and phospholipid remodeling enzymes. Therefore, to establish unequivocally PLD activity in dimethyl sulfoxide-differentiated HL-60 granulocytes, to demonstrate the relative contribution of PLD to phospholipid turnover, and to validate the hypothesis that the formation of phosphatidylethanol is an expression of PLD-catalyzed transphosphatidylation, we have developed methodologies to label HL-60 granulocytes in 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkyl-PC) with 32P without labeling cellular ATP. These methodologies involve (a) synthesis of alkyl-lysoPC containing 32P by a combination of enzymatic and chemical procedures and (b) incubation of HL-60 granulocytes with this alkyl-[32P] lysoPC which enters the cell and becomes acylated into membrane-associated alkyl-[32P]PC. Upon stimulation of these 32P-labeled cells with the chemotactic peptide, N-formyl-Met-Leu-Phe (fMLP), alkyl-[32P]phosphatidic acid (alkyl-[32P]PA) is formed rapidly. Because, under these conditions, cellular ATP has not been labeled with 32P, alkyl-[32P]PA must be formed via PLD-catalyzed hydrolysis of alkyl-[32P]PC at the terminal phosphodiester bond. This result conclusively demonstrates fMLP-induced activation of PLD in HL-60 granulocytes. These 32P-labeled HL-60 granulocytes have also been stimulated in the presence of ethanol to produce alkyl-[32P]phosphatidylethanol (alkyl-[32P]PEt). Formation of alkyl-[32P]PEt parallels that of alkyl-[32P]PA with respect to time course, fMLP concentration, inhibition by a specific fMLP antagonist (t-butoxycarbonyl-Met-Leu-Phe), and Ca2+ concentration

  20. Enantioselective Synthesis of α-Mercapto-β-amino Esters via Rh(II)/Chiral Phosphoric Acid-Cocatalyzed Three-Component Reaction of Diazo Compounds, Thiols, and Imines.

    Xiao, Guolan; Ma, Chaoqun; Xing, Dong; Hu, Wenhao

    2016-12-02

    An enantioselective method for the synthesis of α-mercapto-β-amino esters has been developed via a rhodium(II)/chiral phosphoric acid-cocatalyzed three-component reaction of diazo compounds, thiols, and imines. This transformation is proposed to proceed through enantioselective trapping of the sulfonium ylide intermediate generated in situ from the diazo compound and thiol by the phosphoric acid-activated imine. With this method, a series of α-mercapto-β-amino esters were obtained in good yields with moderate to good stereoselectivities.

  1. Room-Temperature Alternative to the Arbuzov Reaction: The Reductive Deoxygenation of Acyl Phosphonates

    Kedrowski, Sean M. A.; Dougherty, Dennis A.

    2010-01-01

    The reductive deoxygenation of acyl phosphonates using a Wolff−Kishner-like sequence is described. This transformation allows direct access to alkyl phosphonates from acyl phosphonates at room temperature. The method can be combined with acyl phosphonate synthesis into a one pot, four-step procedure for the conversion of carboxylic acids into alkyl phosphonates. The methodology works well for a variety of aliphatic acids and shows a functional group tolerance similar to that of other hydrazon...

  2. Structure of the Francisella tularensis enoyl-acyl carrier protein reductase (FabI) in complex with NAD+ and triclosan

    Mehboob, Shahila; Truong, Kent; Santarsiero, Bernard D.; Johnson, Michael E.

    2010-01-01

    Structure of the ternary complex of F. tularensis enoyl-acyl carrier protein reductase reveals the structure of the substrate binding loop whose electron density was missing in an earlier structure, and demonstrates a shift in the position of the NAD + cofactor. Enoyl-acyl carrier protein reductase (FabI) catalyzes the last rate-limiting step in the elongation cycle of the fatty-acid biosynthesis pathway and has been validated as a potential antimicrobial drug target in Francisella tularensis. The development of new antibiotic therapies is important both to combat potential drug-resistant bioweapons and to address the broader societal problem of increasing antibiotic resistance among many pathogenic bacteria. The crystal structure of FabI from F. tularensis (FtuFabI) in complex with the inhibitor triclosan and the cofactor NAD + has been solved to a resolution of 2.1 Å. Triclosan is known to effectively inhibit FabI from different organisms. Precise characterization of the mode of triclosan binding is required to develop highly specific inhibitors. Comparison of our structure with the previously determined FtuFabI structure which is bound to only NAD + reveals the conformation of the substrate-binding loop, electron density for which was missing in the earlier structure, and demonstrates a shift in the conformation of the NAD + cofactor. This shift in the position of the phosphate groups allows more room in the active site for substrate or inhibitor to bind and be better accommodated. This information will be crucial for virtual screening studies to identify novel scaffolds for development into new active inhibitors

  3. Mechanism of MenE inhibition by acyl-adenylate analogues and discovery of novel antibacterial agents.

    Matarlo, Joe S; Evans, Christopher E; Sharma, Indrajeet; Lavaud, Lubens J; Ngo, Stephen C; Shek, Roger; Rajashankar, Kanagalaghatta R; French, Jarrod B; Tan, Derek S; Tonge, Peter J

    2015-10-27

    MenE is an o-succinylbenzoyl-CoA (OSB-CoA) synthetase in the bacterial menaquinone biosynthesis pathway and is a promising target for the development of novel antibacterial agents. The enzyme catalyzes CoA ligation via an acyl-adenylate intermediate, and we have previously reported tight-binding inhibitors of MenE based on stable acyl-sulfonyladenosine analogues of this intermediate, including OSB-AMS (1), which has an IC50 value of ≤25 nM for Escherichia coli MenE. Herein, we show that OSB-AMS reduces menaquinone levels in Staphylococcus aureus, consistent with its proposed mechanism of action, despite the observation that the antibacterial activity of OSB-AMS is ∼1000-fold lower than the IC50 for enzyme inhibition. To inform the synthesis of MenE inhibitors with improved antibacterial activity, we have undertaken a structure-activity relationship (SAR) study stimulated by the knowledge that OSB-AMS can adopt two isomeric forms in which the OSB side chain exists either as an open-chain keto acid or a cyclic lactol. These studies revealed that negatively charged analogues of the keto acid form bind, while neutral analogues do not, consistent with the hypothesis that the negatively charged keto acid form of OSB-AMS is the active isomer. X-ray crystallography and site-directed mutagenesis confirm the importance of a conserved arginine for binding the OSB carboxylate. Although most lactol isomers tested were inactive, a novel difluoroindanediol inhibitor (11) with improved antibacterial activity was discovered, providing a pathway toward the development of optimized MenE inhibitors in the future.

  4. Rh-catalyzed linear hydroformylation of styrene

    Boymans, E.H.; Janssen, M.C.C.; Mueller, C.; Lutz, M.; Vogt, D.

    2012-01-01

    Usually the Rh-catalyzed hydroformylation of styrene predominantly yields the branched, chiral aldehyde. An inversion of regioselectivity can be achieved using strong p-acceptor ligands. Binaphthol-based diphosphite and bis(dipyrrolyl-phosphorodiamidite) ligands were applied in the Rh-catalyzed

  5. Solid-phase receptor-based assay for the detection of cyclic imines by chemiluminescence, fluorescence, or colorimetry.

    Rodríguez, Laura P; Vilariño, Natalia; Molgó, Jordi; Aráoz, Rómulo; Antelo, Alvaro; Vieytes, Mercedes R; Botana, Luis M

    2011-08-01

    The spirolides and gymnodimines are marine phycotoxins included in the group of cyclic imines. The toxicity of these compounds to humans is still unknown, although their toxicity by intraperitoneal injection in rodents is very high. A receptor-based method was developed using the competition of the 13-desmethyl spirolide C with biotin-labeled α-bungarotoxin for binding to nicotinic acetylcholine receptors and the immobilization of the α-bungarotoxin-receptor complex on streptavidin-coated surfaces. The quantification of the immobilized receptor can be achieved using a specific antibody. Finally, after the addition of a secondary antibody labeled with horseradish peroxidase, three alternative substrates of this enzyme generate a chemiluminescent, fluorescent, or colorimetric signal. The assay performs well in shellfish extracts and the detection range is 5-150 nM of 13-desmethyl spirolide C in shellfish extracts, which is at least 5 times more sensitive than the existing fluorescence polarization assay. This assay can also detect gymnodimine, although with 10 times lower sensitivity than the spirolide. The detection of cyclic imines with microplate assays would be useful for screening purposes in order to reduce the number of samples to be processed by bioassays or analytical methods.

  6. Discovery of a potent and orally available acyl-CoA: cholesterol acyltransferase inhibitor as an anti-atherosclerotic agent: (4-phenylcoumarin)acetanilide derivatives.

    Ogino, Masaki; Fukui, Seiji; Nakada, Yoshihisa; Tokunoh, Ryosuke; Itokawa, Shigekazu; Kakoi, Yuichi; Nishimura, Satoshi; Sanada, Tsukasa; Fuse, Hiromitsu; Kubo, Kazuki; Wada, Takeo; Marui, Shogo

    2011-01-01

    Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular enzyme that catalyzes cholesterol esterification. ACAT inhibitors are expected to be potent therapeutic agents for the treatment of atherosclerosis. A series of potent ACAT inhibitors based on an (4-phenylcoumarin)acetanilide scaffold was identified. Evaluation of the structure-activity relationships of a substituent on this scaffold, with an emphasis on improving the pharmacokinetic profile led to the discovery of 2-[7-chloro-4-(3-chlorophenyl)-6-methyl-2-oxo-2H-chromen-3-yl]-N-[4-chloro-2-(trifluoromethyl)phenyl]acetamide (23), which exhibited potent ACAT inhibitory activity (IC50=12 nM) and good pharmacokinetic profile in mice. Compound 23 also showed regressive effects on atherosclerotic plaques in apolipoprotein (apo)E knock out (KO) mice at a dose of 0.3 mg/kg per os (p.o.).

  7. New acylated flavone and cyanogenic glycosides from Linum grandiflorum

    Mohammed, Magdy M. D.; Christensen, Lars Porskjær; Ibrahim, Nabaweya A.

    2009-01-01

    The first investigation of Linum grandiflorum resulted in the isolation of one new acylated flavone O-diglycoside known as luteolin 7-O-a-D-(6000-E-feruloyl)glucopyranosyl (1!2)--D-glucopyranoside, and one new cyanogenic glycoside known as 2-[(30-isopropoxy-O--D-glucopyranosyl)oxy]-2......-methylbutanenitrile, together with four known flavonoid glycosides, three known cyanogenic glycosides and one alkyl glycoside. The new compounds were structurally elucidated via the extensive 1D, 2D NMR and DIFNOE together with ESI-TOFCID-MS/MS and HR-MALDI/MS....

  8. Phosphorylation and Acetylation of Acyl-CoA Synthetase- I

    Frahm, Jennifer L; Li, Lei O; Grevengoed, Trisha J

    2011-01-01

    Long chain acyl-CoA synthetase 1 (ACSL1) contributes 50 to 90% of total ACSL activity in liver, adipose tissue, and heart and appears to direct the use of long chain fatty acids for energy. Although the functional importance of ACSL1 is becoming clear, little is understood about its post...... and acetylated amino acids by mass spectrometry. We then compared these results to the post-translational modifications observed in vivo in liver and brown adipose tissue after mice were fasted or exposed to a cold environment. We identified universal N-terminal acetylation, 15 acetylated lysines, and 25...

  9. Evolution of the acyl-CoA binding protein (ACBP)

    Burton, Mark; Rose, Timothy M; Faergeman, Nils J

    2005-01-01

    -CoA pool size, donation of acyl-CoA esters for beta-oxidation, vesicular trafficking, complex lipid synthesis and gene regulation. In the present study, we delineate the evolutionary history of ACBP to get a complete picture of its evolution and distribution among species. ACBP homologues were identified...... duplication and/or retrotransposition events. The ACBP protein is highly conserved across phylums, and the majority of ACBP genes are subjected to strong purifying selection. Experimental evidence indicates that the function of ACBP has been conserved from yeast to humans and that the multiple lineage...

  10. delta 6 Hexadecenoic acid is synthesized by the activity of a soluble delta 6 palmitoyl-acyl carrier protein desaturase in Thunbergia alata endosperm.

    Cahoon, E B; Cranmer, A M; Shanklin, J; Ohlrogge, J B

    1994-11-04

    delta 6 Hexadecenoic acid (16:1 delta 6) composes more than 80% of the seed oil of Thunbergia alata. Studies were conducted to determine the biosynthetic origin of the double bond of this unusual fatty acid. Assays of fractions of developing T. alata seed endosperm with [1-14C]palmitoyl (16:0)-acyl carrier protein (ACP) revealed the presence of a soluble delta 6 desaturase activity. This activity was greatest when 16:0-ACP was provided as a substrate, whereas no desaturation of the coenzyme A ester of this fatty acid was detected. In addition, delta 6 16:0-ACP desaturase activity in T. alata endosperm extracts was dependent on the presence of ferredoxin and molecular oxygen and was stimulated by catalase. To further characterize this enzyme, a cDNA encoding a diverged acyl-ACP desaturase was isolated from a T. alata endosperm cDNA library using polymerase chain reaction with degenerate oligonucleotides corresponding to conserved amino acid sequences in delta 9 stearoyl (18:0)- and delta 4 16:0-ACP desaturases. The primary structure of the mature peptide encoded by this cDNA shares 66% identity with the mature castor delta 9 18:0-ACP desaturase and 57% identity with the mature coriander delta 4 16:0-ACP desaturase. Extracts of Escherichia coli that express the T. alata cDNA catalyzed the delta 6 desaturation of 16:0-ACP. These results demonstrate that 16:1 delta 6 in T. alata endosperm is formed by the activity of a soluble delta 6 16:0-ACP desaturase that is structurally related to the delta 9 18:0- and delta 4 16:0-ACP desaturases. Implications of this work to an understanding of active site structures of acyl-ACP desaturases are discussed.

  11. Pyridine group assisted addition of diazo-compounds to imines in the 3-CC reaction of 2-aminopyridines, aldehydes, and diazo-compounds.

    Gulevich, Anton V; Helan, Victoria; Wink, Donald J; Gevorgyan, Vladimir

    2013-02-15

    A novel three-component coupling (3-CC) reaction of 2-aminoazines, aromatic aldehydes, and diazo-compounds producing polyfunctional β-amino-α-diazo-compounds has been developed. The reaction features an unprecedented heterocycle-assisted addition of a diazo-compound to an imine. The obtained diazoesters were efficiently converted into valuable heterocycles as well as β-amino acid derivatives.

  12. Compositional analysis of nitrile terminated poly(propylene imine) dendrimers by high-performance liquid chromatography combined with electrospray mass spectrometry

    van der Wal, S; Mengerink, Y; Brackman, JC; de Brabander, EMM; Jeronimus-Stratingh, CM; Bruins, AP

    1998-01-01

    Separation methods for nitrile terminated poly(propylene imine) dendrimers were developed to monitor and optimize their large scale production. Detailed analyses of defects within a dendrimer generation were performed by HPLC at alkaline pH (sodium hydroxide) on a polymer-based column or at neutral

  13. In situ generation of N-Boc-protected alkenyl imines: controlling the E/Z geometry of alkenyl moieties in the Mukaiyama-Mannich reaction.

    Bai, Jian-Fei; Sasagawa, Hajime; Yurino, Taiga; Kano, Taichi; Maruoka, Keiji

    2017-07-18

    Readily available Boc-protected Z-alkenyl aminals could be used as Z-alkenyl and E-alkenyl imine precursors under acidic conditions. In the Mukaiyama-Mannich reaction of Z-alkenyl Boc-aminals, the E/Z geometry of the products was controlled by the catalyst used. The present method was also applied to asymmetric Mukaiyama-Mannich reactions.

  14. Photocatalytic organic transformation by layered double hydroxides: highly efficient and selective oxidation of primary aromatic amines to their imines under ambient aerobic conditions.

    Yang, Xiu-Jie; Chen, Bin; Li, Xu-Bing; Zheng, Li-Qiang; Wu, Li-Zhu; Tung, Chen-Ho

    2014-06-25

    We report the first application of layered double hydroxide as a photocatalyst in the transformation of primary aromatic amines to their corresponding imines with high efficiency and selectivity by using oxygen in an air atmosphere as a terminal oxidant under light irradiation.

  15. Modulation of cellulase activity by charged lipid bilayers with different acyl chain properties for efficient hydrolysis of ionic liquid-pretreated cellulose.

    Mihono, Kai; Ohtsu, Takeshi; Ohtani, Mai; Yoshimoto, Makoto; Kamimura, Akio

    2016-10-01

    The stability of cellulase activity in the presence of ionic liquids (ILs) is critical for the enzymatic hydrolysis of insoluble cellulose pretreated with ILs. In this work, cellulase was incorporated in the liposomes composed of negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and zwitterionic phosphatidylcholines (PCs) with different length and degree of unsaturation of the acyl chains. The liposomal cellulase-catalyzed reaction was performed at 45°C in the acetate buffer solution (pH 4.8) with 2.0g/L CC31 as cellulosic substrate. The crystallinity of CC31 was reduced by treating with 1-butyl-3-methylimidazolium chloride ([Bmim]Cl) at 120°C for 30min. The liposomal cellulase continuously catalyzed hydrolysis of the pretreated CC31 for 48h producing glucose in the presence of 15wt% [Bmim]Cl. The charged lipid membranes were interactive with [Bmim](+), as elucidated by the [Bmim]Cl-induced alterations in fluorescence polarization of the membrane-embedded 1,6-diphenyl-1,3,5-hexatriene (DPH) molecules. The charged membranes offered the microenvironment where inhibitory effects of [Bmim]Cl on the cellulase activity was relieved. The maximum glucose productivity GP of 10.8 mmol-glucose/(hmol-lipid) was obtained at the reaction time of 48h with the cellulase incorporated in the liposomes ([lipid]=5.0mM) composed of 50mol% POPG and 1,2-dilauroyl-sn-glycero-3-phosohocholine (DLPC) with relatively short and saturated acyl chains. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Ruthenium(II)-Catalyzed C-H Activation of Imidamides and Divergent Couplings with Diazo Compounds: Substrate-Controlled Synthesis of Indoles and 3H-Indoles.

    Li, Yunyun; Qi, Zisong; Wang, He; Yang, Xifa; Li, Xingwei

    2016-09-19

    Indoles are an important structural motif that is commonly found in biologically active molecules. In this work, conditions for divergent couplings between imidamides and acceptor-acceptor diazo compounds were developed that afforded NH indoles and 3H-indoles under ruthenium catalysis. The coupling of α-diazoketoesters afforded NH indoles by cleavage of the C(N2 )-C(acyl) bond whereas α-diazomalonates gave 3H-indoles by C-N bond cleavage. This reaction constitutes the first intermolecular coupling of diazo substrates with arenes by ruthenium-catalyzed C-H activation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Nickel-Catalyzed C–O Bond-Cleaving Alkylation of Esters: Direct Replacement of the Ester Moiety by Functionalized Alkyl Chains

    Liu, Xiangqian; Jia, Jiaqi; Rueping, Magnus

    2017-01-01

    Two efficient protocols for the nickel-catalyzed aryl–alkyl cross-coupling reactions using esters as coupling components have been established. The methods enable the selective oxidative addition of nickel to acyl C–O and aryl C–O bonds and allow the aryl–alkyl cross-coupling via decarbonylative bond cleavage or through cleavage of a C–O bond with high efficiency and good functional group compatibility. The protocols allow the streamlined, unconventional utilization of widespread ester groups and their precursors, carboxylic acids and phenols, in synthetic organic chemistry.

  18. Nickel-Catalyzed C–O Bond-Cleaving Alkylation of Esters: Direct Replacement of the Ester Moiety by Functionalized Alkyl Chains

    Liu, Xiangqian

    2017-06-07

    Two efficient protocols for the nickel-catalyzed aryl–alkyl cross-coupling reactions using esters as coupling components have been established. The methods enable the selective oxidative addition of nickel to acyl C–O and aryl C–O bonds and allow the aryl–alkyl cross-coupling via decarbonylative bond cleavage or through cleavage of a C–O bond with high efficiency and good functional group compatibility. The protocols allow the streamlined, unconventional utilization of widespread ester groups and their precursors, carboxylic acids and phenols, in synthetic organic chemistry.

  19. Can laccases catalyze bond cleavage in lignin?

    Munk, Line; Sitarz, Anna Katarzyna; Kalyani, Dayanand

    2015-01-01

    illustrations of the putative laccase catalyzed reactions, including the possible reactions of the reactive radical intermediates taking place after the initial oxidation of the phenol-hydroxyl groups, we show that i) Laccase activity is able to catalyze bond cleavage in low molecular weight phenolic lignin......-substituted phenols, benzenethiols, polyphenols, and polyamines, which may be oxidized. In addition, the currently available analytical methods that can be used to detect enzyme catalyzed changes in lignin are summarized, and an improved nomenclature for unequivocal interpretation of the action of laccases on lignin...

  20. Accumulation of N-acyl-ethanolamine phospholipids in rat brains during post-decapitative ischemia

    Moesgaard, B.; Hansen, Harald S.; Jaroszewski, J.W.

    1999-01-01

    -phospho(N-acyl)-ethanolamine (NAPE(PLAS)), respectively, by spiking with authentic materials. Additionally, the identification was verified by thin-layer chromatography, which also showed the accumulation of N-acyl-ethanolamine phospholipids. The use of K-EDTA instead of the commonly used Cs...

  1. Identification of N-acyl-fumonisin B1 as new cytotoxic metabolites of fumonisin mycotoxins.

    Harrer, Henning; Laviad, Elad L; Humpf, Hans Ulrich; Futerman, Anthony H

    2013-03-01

    Fumonisins are mycotoxins produced by Fusarium species. The predominant derivative, fumonisin B1 (FB1), occurs in food and feed and is of health concern due to its hepatotoxic and carcinogenic effects. However, the role of FB1 metabolites on the mechanism of the toxicity, the inhibition of the ceramide synthesis, is unknown. The aim of this study was to identify new fumonisin metabolites and to evaluate their cytotoxic potential. MS, molecular biology, and in vitro enzyme assays were used to investigate fumonisin metabolism in mammalian cells overexpressing human ceramide synthase (CerS) genes. N-acyl-FB1 derivatives were detected as new metabolites in cultured cells at levels of up to 10 pmol/mg of protein. The N-acylation of FB1 and hydrolyzed FB1 was analyzed in several cell lines, including cells overexpressing CerS. The acyl-chain length of the N-acyl fumonisins depends on the CerS isoform acylating them. The N-acyl fumonisins are more cytotoxic than the parent fumonisin B1. The identification of N-acyl fumonisins with various acyl chain lengths together with the observed cytotoxicity of these compounds is a new aspect of fumonisin-related toxicity. Therefore, these new metabolites might play an important role in the mode of action of fumonisins. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. 1,5-Anhydro-D-fructose: regioselective acylation with fatty acids

    Lundt, Inge; Andersen, Søren Møller; Marcussen, Jan

    1999-01-01

    Regioselective acylation of 1,5-anhydro-D-fructose was performed with dodecanoic acid to give 1,5-anhydro-6-O-dodecanoyl-D-fructose, chemically in 50% yield and enzymatically in quantitative yield. Quantitative conversions were also obtained using hexadecanoic and octadecanoic acids as acyl donors...

  3. A simple, effective, green method for regioselective 3-acylation of unprotected indoles

    Tran, Phuong Huong; Tran, Hai N.; Hansen, Poul Erik

    2015-01-01

    A fast and green method is developed for regioselective acylation of indoles in the 3-position without the need for protection of the NH position. The method is based on Friedel-Crafts acylation using acid anhydrides. The method has been optimized, and Y(OTf)3 in catalytic amounts is found...

  4. Cis–Trans Configuration of Coumaric Acid Acylation Affects the Spectral and Colorimetric Properties of Anthocyanins

    Gregory T. Sigurdson

    2018-03-01

    Full Text Available The color expression of anthocyanins can be affected by a variety of environmental factors and structural characteristics. Anthocyanin acylation (type and number of acids is known to be key, but the influence of acyl isomers (with unique stereochemistries remains to be explored. The objective of this study was to investigate the effects of cis–trans configuration of the acylating group on the spectral and colorimetric properties of anthocyanins. Petunidin-3-rutinoside-5-glucoside (Pt-3-rut-5-glu and Delphinidin-3-rutinoside-5-glucoside (Dp-3-rut-5-glu and their cis and trans coumaroylated derivatives were isolated from black goji and eggplant, diluted in pH 1–9 buffers, and analyzed spectrophotometrically (380–700 nm and colorimetrically (CIELAB during 72 h of storage (25 °C, dark. The stereochemistry of the acylating group strongly impacted the spectra, color, and stability of the Dp and Pt anthocyanins. Cis acylated pigments exhibited the greatest λmax in all pH, as much as 66 nm greater than their trans counterparts, showing bluer hues. Cis acylation seemed to reduce hydration across pH, increasing color intensity, while trans acylation generally improved color retention over time. Dp-3-cis-p-cou-rut-5-glu exhibited blue hues even in pH 5 (C*ab = 10, hab = 256° where anthocyanins are typically colorless. Cis or trans double bond configurations of the acylating group affected anthocyanin spectral and stability properties.

  5. Suppression of acyl migration in enzymatic production of structured lipids through temperature programming

    Yang, Tiankui; Fruekilde, Maj-Britt; Xu, Xuebing

    2005-01-01

    Acyl migration in the glycerol backbone often leads to the increase of by-products in the enzymatic production of specific structured lipids. Acyl migration is a thermodynamic process and is very difficult to stop fully in actual reactions. The objective of this study was to investigate...

  6. Mechanistic aspects of the metal catalyzed alternating copolymerization of epoxides and carbon monoxide.

    Allmendinger, Markus; Molnar, Ferenc; Zintl, Manuela; Luinstra, Gerrit A; Preishuber-Pflügl, Peter; Rieger, Bernhard

    2005-09-05

    The cobalt-catalyzed alternating copolymerization of epoxides and CO is a novel, direct approach to aliphatic polyesters, such as poly(hydroxybutyrate) (PHB). This reaction was found to be catalyzed by Ph3Si[Co(CO)4] (4) and pyridine affording in a first step the stable mono-insertion product Ph3Si-O-CH(CH3)-CH2-CO-Co(CO)4 (5). However, a profound mechanistic understanding, especially of the role of pyridine as the key component for the polymerization reaction was missing. ATR-IR online monitoring under catalytic conditions and DFT calculations were used to show that an acylpyridinium cation is formed by cleavage of the cobalt-acyl bond of 5 in the presence of pyridine. The Lewis acid thus generated activates the next incoming epoxide monomer for ring opening through [Co(CO)4]-. The catalytic cycle is completed by a subsequent CO insertion in the new cobalt-alkyl bond. The calculations are used to explore the energetic hypersurface of the polymerization reaction and are complemented by extended experimental investigations that also support the mechanistic hypotheses.

  7. Synthesis and Bioactivity of Pyrazole Acyl Thiourea Derivatives

    Jian Wu

    2012-05-01

    Full Text Available Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine and ethyl acetoacetate. The key 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl chloride intermediates 4 were first generated in four steps through cyclization, formylation, oxidation and acylation. Thess were then reacted with ammonium thiocyanate in the presence of PEG-400 to afford 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl isothiocyanates 5. Subsequent reaction with fluorinated aromatic amines resulted in the formation of the title compounds. The synthesized compound were unequivocally characterized by IR, 1H-NMR, 13C-NMR and elemental analysis and some of the synthesized compounds displayed good antifungal activities against Gibberella zeae, Fusarium oxysporum, Cytospora mandshurica and anti-TMV activity in preliminary antifungal activity tests.

  8. N-acyl phosphatidylethanolamines affect the lateral distribution of cholesterol in membranes

    Térová, B.; Slotte, J.P.; Petersen, G.

    2005-01-01

    -acyl-POPE) or N-acyl-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (N-acyl-DPPE), and how the molecules interacted with cholesterol. The gel ¿ liquid crystalline transition temperature of sonicated N-acyl phosphatidylethanolamine vesicles in water correlated positively with the number of palmitic acyl chains...... in the molecules. Based on diphenylhexatriene steady state anisotropy measurements, the presence of 33 mol% cholesterol in the membranes removed the phase transition from N-oleoyl-POPE bilayers, but failed to completely remove it from N-palmitoyl-DPPE and N-palmitoyl-POPE bilayers, suggesting rather weak...... interaction of cholesterol with the N-saturated NAPEs. The rate of cholesterol desorption from mixed monolayers containing N-palmitoyl-DPPE and cholesterol (1:1 molar ratio) was much higher compared to cholesterol/DPPE binary monolayers, suggesting a weak cholesterol interaction with N-palmitoyl-DPPE also...

  9. Fluorescently labelled bovine acyl-CoA-binding protein acting as an acyl-CoA sensor: interaction with CoA and acyl-CoA esters and its use in measuring free acyl-CoA esters and non-esterified fatty acids

    Wadum, M.C.; Villadsen, J.K.; Feddersen, S.

    2002-01-01

    methods for the determination of free acyl-CoA concentrations. No such method is presently available. In the present study, we describe the synthesis of two acyl-CoA sensors for measuring free acyl-CoA concentrations using acyl-CoA-binding protein as a scaffold. Met24 and Ala53 of bovine acyl...... of ligand (excitation 387nm). Titration of FACI-24 and FACI-53 with hexadecanoyl-CoA and dodecanoyl-CoA increased the fluorescence yield 5.5-and 4.7-fold at 460 and 495nm respectively. FACI-24 exhibited a high, and similar increase in, fluorescence yield at 460nm upon binding of C14-C20 saturated...

  10. Acylation of salmon calcitonin modulates in vitro intestinal peptide flux through membrane permeability enhancement

    Trier, Sofie; Linderoth, Lars; Bjerregaard, Simon

    2015-01-01

    hypothesize that tailoring the acylation may be used to optimize intestinal translocation. This work aims to characterize acylated analogues of the therapeutic peptide salmon calcitonin (sCT), which lowers blood calcium, by systematically increasing acyl chain length at two positions, in order to elucidate...... to be optimal, as elongating the chain causes greater binding to the cell membrane but similar permeability, and we speculate that increasing the chain length further may decrease the permeability. In conclusion, acylated sCT acts as its own in vitro intestinal permeation enhancer, with reversible effects...... on Caco-2 cells, indicating that acylation of sCT may represent a promising tool to increase intestinal permeability without adding oral permeation enhancers....

  11. Modeling evolution of hydrogen bonding and stabilization of transition states in the process of cocaine hydrolysis catalyzed by human butyrylcholinesterase.

    Gao, Daquan; Zhan, Chang-Guo

    2006-01-01

    Molecular dynamics (MD) simulations and quantum mechanical/molecular mechanical (QM/MM) calculations were performed on the prereactive enzyme-substrate complex, transition states, intermediates, and product involved in the process of human butyrylcholinesterase (BChE)-catalyzed hydrolysis of (-)-cocaine. The computational results consistently reveal a unique role of the oxyanion hole (consisting of G116, G117, and A199) in BChE-catalyzed hydrolysis of cocaine, compared to acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylcholine. During BChE-catalyzed hydrolysis of cocaine, only G117 has a hydrogen bond with the carbonyl oxygen (O31) of the cocaine benzoyl ester in the prereactive BChE-cocaine complex, and the NH groups of G117 and A199 are hydrogen-bonded with O31 of cocaine in all of the transition states and intermediates. Surprisingly, the NH hydrogen of G116 forms an unexpected hydrogen bond with the carboxyl group of E197 side chain and, therefore, is not available to form a hydrogen bond with O31 of cocaine in the acylation. The NH hydrogen of G116 is only partially available to form a weak hydrogen bond with O31 of cocaine in some structures involved in the deacylation. The change of the estimated hydrogen-bonding energy between the oxyanion hole and O31 of cocaine during the reaction process demonstrates how the protein environment can affect the energy barrier for each step of the BChE-catalyzed hydrolysis of cocaine. These insights concerning the effects of the oxyanion hole on the energy barriers provide valuable clues on how to rationally design BChE mutants with a higher catalytic activity for the hydrolysis of (-)-cocaine. 2005 Wiley-Liss, Inc.

  12. Muon-catalyzed fusion revisited

    Anon.

    1984-12-15

    A negative muon can induce nuclear fusion in the reaction of deuteron and triton nuclei giving a helium nucleus, a neutron and an emerging negative muon. The muon forms a tightlybound deuteron-triton-muon molecule and fusion follows in about 10{sup -12}s. Then the muon is free again to induce further reactions. Thus the muon can serve as a catalyst for nuclear fusion, which can proceed without the need for the high temperatures which are needed in the confinement and inertial fusion schemes. At room temperature, up to 80 fusions per muon have recently been observed at the LAMPF machine at Los Alamos, and it is clear that this number can be exceeded. These and other results were presented at a summer Workshop on Muon-Catalyzed Fusion held in Jackson, Wyoming. Approximately fifty scientists attended from Austria, Canada, India, Italy, Japan, South Africa, West Germany, and the United States. The Workshop itself is symbolic of the revival of interest in this subject.

  13. Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling

    Færgeman, Nils J.; Knudsen, J

    1997-01-01

    (Ki for acyl-CoA is 5 nM) indicates strongly that the free cytosolic acyl-CoA concentration is below 5 nM under these conditions. Only a limited number of the reported experiments on the effects of acyl-CoA on cellular functions and enzymes have been carried out at low physiological concentrations...

  14. Relationships between acylated ghrelin with growth hormone, insulin resistance, lipid profile, and cardio respiratory function in lean and obese men

    Hasan Matin Homaee

    2011-01-01

    Conclusions: Obese and lean inactive young men had different levels of acylated ghrelin, GH, insulin, insulin resistance index, cardiorespiratory function and body fat percent. Body fat percent, insulin, and GH levels appear to be best determinant factors of acylated ghrelin levels. Also, in both obese and lean young men, higher levels of cardiovascular function were associated with higher levels of acylated ghrelin.

  15. Long-chain acyl-CoA-dependent regulation of gene expression in bacteria, yeast and mammals

    Black, P N; Færgeman, Nils J.; DiRusso, C C

    2000-01-01

    ). Both repression and activation are dependent upon the function of either of the acyl-CoA synthetases Faa1p or Faa4p. In mammals, purified hepatocyte nuclear transcription factor 4alpha (HNF-4alpha) like E. coli FadR, binds long chain acyl-CoA directly. Coexpression of HNF-4alpha and acyl-CoA synthetase...

  16. Iron Catalyzed Cycloaddition of Alkynenitriles and Alkynes

    D’Souza, Brendan R.; Lane, Timothy K.

    2011-01-01

    The combination of Fe(OAc)2 and an electron-donating, sterically-hindered pyridyl bisimine ligand catalyzes the cycloaddition of alkynenitriles and alkynes. A variety of substituted pyridines were obtained in good yields. PMID:21557582

  17. Reactions of Cp2MCl2 (M=Ti or Zr with Imine-Oxime Ligands. Formation of Metallacycles

    C. Tripathi

    2005-07-01

    Full Text Available The reactions of bis(cyclopentadienyltitanium(IV/zirconium(IV dichloridewith a series of imine-oxime ligands (LH2, derived by condensing benzil-α-monoxime and2-phenylenediamine, 4-phenylenediamine, 4-methyl-2-phenylenediamine, 2,6-diamino-pyridine, have been studied in anhydrous tetrahydrofuran in the presence of base andmetallocycles of the [Cp2M(L] (M=Ti or Zr type have been isolated. Tentative structureshave been proposed for the products based on elemental analysis, electrical conductance andspectral (electronic, IR and 1H-NMR data. Proton NMR spectra indicate that on the NMRtime scale there is rapid rotation of the cyclopentadienyl ring around the metal-ring axis at25oC. Studies were conducted to assess the growth inhibiting potential of the complexessynthesized and the ligands against various bacterial strains.

  18. Morphological mutations induced by gamma rays, ethylene imine and N-nitroso-N-ethyl urea in lentil (Lens culinaris medik.)

    Solanki, I.S.; Sharma, B.

    2003-01-01

    Dry and healthy seeds of a large seeded lentil cv, 'Precoz Selection', were treated with three doses each of gamma rays, ethylene imine (EI) and N-nitroso-N-ethyl urea (NEU). Based on the frequency of morphological mutations, the mutagens were arranged in the order: NEU > EI >. Gamma rays and dose-dependent relationship was observed in the case of gamma rays (5 kR 1 damage groups induced morphological mutations in the order: HH > HL > LH > LL. The morphological mutations included changes for growth habit, foliage, plant height and maturity and flowering behaviour. A mild relative mutagenic specificity and differences in mutability of genes for different traits were observed, In general the spectrum of morphological mutations was not influenced by the groups of M 1 damage, except that some mutation types occurred more frequently, than others in certain groups. (author)

  19. Ruthenium-Catalyzed Aerobic Oxidation of Amines.

    Ray, Ritwika; Hazari, Arijit Singha; Lahiri, Goutam Kumar; Maiti, Debabrata

    2018-01-18

    Amine oxidation is one of the fundamental reactions in organic synthesis as it leads to a variety of value-added products such as oximes, nitriles, imines, and amides among many others. These products comprise the key N-containing building blocks in the modern chemical industry, and such transformations, when achieved in the presence of molecular oxygen without using stoichiometric oxidants, are much preferred as they circumvent the production of unwanted wastes. In parallel, the versatility of ruthenium catalysts in various oxidative transformations is well-documented. Herein, this review focuses on aerobic oxidation of amines specifically by using ruthenium catalysts and highlights the major achievements in this direction and challenges that still need to be addressed. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Central and peripheral des-acyl ghrelin regulates body temperature in rats.

    Inoue, Yoshiyuki; Nakahara, Keiko; Maruyama, Keisuke; Suzuki, Yoshiharu; Hayashi, Yujiro; Kangawa, Kenji; Murakami, Noboru

    2013-01-04

    In the present study using rats, we demonstrated that central and peripheral administration of des-acyl ghrelin induced a decrease in the surface temperature of the back, and an increase in the surface temperature of the tail, although the effect of peripheral administration was less marked than that of central administration. Furthermore, these effects of centrally administered des-acyl ghrelin could not be prevented by pretreatment with [D-Lys3]-GHRP-6 GH secretagogue receptor 1a (GHS-R1a) antagonists. Moreover, these actions of des-acyl ghrelin on body temperature were inhibited by the parasympathetic nerve blocker methylscopolamine but not by the sympathetic nerve blocker timolol. Using immunohistochemistry, we confirmed that des-acyl ghrelin induced an increase of cFos expression in the median preoptic nucleus (MnPO). Additionally, we found that des-acyl ghrelin dilated the aorta and tail artery in vitro. These results indicate that centrally administered des-acyl ghrelin regulates body temperature via the parasympathetic nervous system by activating neurons in the MnPO through interactions with a specific receptor distinct from the GHS-R1a, and that peripherally administered des-acyl ghrelin acts on the central nervous system by passing through the blood-brain barrier, whereas it exerts a direct action on the peripheral vascular system. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. A New Acylated Flavonol Glycoside from Chenopodium foliosum

    Zlatina Kokanova-Nedialkova, , , , , and

    2014-07-01

    Full Text Available A new acylated flavonol glycoside, namely gomphrenol-3-O-( 5 '''-O-E-feruloyl-β-D-apiofuranosyl-(1→2[β-D-glucopyranosyl-(1→6]-β-D-glucopyranoside (1 was isolated from the aerial parts of Chenopodium foliosum Asch. The structure of 1 was determined by means of spectroscopic methods (1D and 2D NMR, UV, IR, and HRESIMS. Radical scavenging and antioxidant activities of 1 were established using DPPH and ABTS radicals, FRAP assay and inhibition of lipid peroxidation (LP in linoleic acid system by the ferric thiocyanate method. Compound 1 showed low activity (DPPH and ABTS or lack of activity (FRAP and LP. In combination with CCl 4, 1 reduced the damage caused by the hepatotoxic agent and preserved cell viability and GSH level, decreased LDH leakage and reduced lipid damage. Effects were concentration dependent, most visible at the highest concentration (100 µg/m L , and similar to those of silymarin .

  2. Acylation of proteins with myristic acid occurs cotranslationally

    Wilcox, C.; Hu, J.S.; Olson, E.N.

    1987-01-01

    Several proteins of viral and cellular origin are acylated with myristic acid early during their biogenesis. To investigate the possibility that myristylation occurred cotranslationally, the BC 3 H1 muscle cell line, which contains a broad array of myristylated proteins, was pulse-labeled with [ 3 H]myristic acid. Nascent polypeptide chains covalently associated with transfer RNA were isolated subsequently by ion-exchange chromatography. [ 3 H]Myristate was attached to nascent chains through an amide linkage and was identified by thin-layer chromatography after its release from nascent chains by acid methanolysis. Inhibition of cellular protein synthesis with puromycin resulted in cessation of [ 3 H]myristate-labeling of nascent chains, in agreement with the dependence of this modification on protein synthesis in vivo. These data represent a direct demonstration that myristylation of proteins is a cotranslational modification

  3. Very long-chain acyl-coenzyme A dehydrogenase deficiency

    A. V. Degtyareva

    2014-01-01

    Full Text Available The paper describes a case of a baby with a severe infant form of very long-chain acyl-coenzyme A dehydrogenase deficiency, a very rare genetic disorder. The basis for the disease is a disorder of mitochondrial β-oxidation of long-chain fatty acids. Accumulation of acyl-CoA-derived fatty acids causes a toxic effect on the myocardium and cardiac conduction system, liver, skeletal muscles, and other organs. The development of hypoglycemia is typical. Treatment in the acute period involves the immediately ceased delivery of long-chain triglycerides, the provision of the body with medium-chain triglycerides, and the correction of glycemia. In our observation the baby was born at term with a satisfactory condition in a family with a poor history (the first baby had suddenly died at the age of 3,5 months. The disease manifested itself as bradyarrhythmia and cardiac arrest on day 2 of life. The clinical symptom complex also included hepatomegalia, hypoglycemic episodes, lactate acidosis, and elevated blood levels of cytolytic enzymes and creatine phosphokinase. The diagnosis was suspected on the basis of the high blood values of acylcarnitines (primarily C14:1 and verified by a molecular genetic examination. Syndrome therapy and dietotherapy resulted in the abolishment of the abnormality. At the age of 2 years of life, the infant’s physical, motor, mental, and speech development corresponded to his age although he had mild right-sided hemiparesis. Thus, timely therapy determines the favorable prognosis of the disease even in its severe infant forms. 

  4. An in vitro fatty acylation assay reveals a mechanism for Wnt recognition by the acyltransferase Porcupine.

    Asciolla, James J; Miele, Matthew M; Hendrickson, Ronald C; Resh, Marilyn D

    2017-08-18

    Wnt proteins are a family of secreted signaling proteins that play key roles in regulating cell proliferation in both embryonic and adult tissues. Production of active Wnt depends on attachment of palmitoleate, a monounsaturated fatty acid, to a conserved serine by the acyltransferase Porcupine (PORCN). Studies of PORCN activity relied on cell-based fatty acylation and signaling assays as no direct enzyme assay had yet been developed. Here, we present the first in vitro assay that accurately recapitulates PORCN-mediated fatty acylation of a Wnt substrate. The critical feature is the use of a double disulfide-bonded Wnt peptide that mimics the two-dimensional structure surrounding the Wnt acylation site. PORCN-mediated Wnt acylation was abolished when the Wnt peptide was treated with DTT, and did not occur with a linear (non-disulfide-bonded) peptide, or when the double disulfide-bonded Wnt peptide contained Ala substituted for the Ser acylation site. We exploited this in vitro Wnt acylation assay to provide direct evidence that the small molecule LGK974, which is in clinical trials for managing Wnt-driven tumors, is a bona fide PORCN inhibitor whose IC 50 for inhibition of Wnt fatty acylation in vitro closely matches that for inhibition of Wnt signaling. Side-by-side comparison of PORCN and Hedgehog acyltransferase (HHAT), two enzymes that attach 16-carbon fatty acids to secreted proteins, revealed that neither enzyme will accept the other's fatty acyl-CoA or peptide substrates. These findings illustrate the unique enzyme-substrate selectivity exhibited by members of the membrane-bound O -acyl transferase family. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Decarbonylative Cross-Couplings: Nickel Catalyzed Functional Group Interconversion Strategies for the Construction of Complex Organic Molecules

    Guo, Lin

    2018-04-13

    -mediated decarbonylation process of esters and proposed a reaction mechanism involving a C(acyl)-O bond cleavage and a CO extrusion. Key nickel intermediates were isolated and characterized by Shi and co-workers, supporting the assumption of a nickel/ N-heterocyclic carbene-promoted C(acyl)-O bond activation and functionalization. Our combined experimental and computational study of a ligand-controlled chemoselective nickel-catalyzed cross-coupling of aromatic esters with alkylboron reagents provided further insight into the reaction mechanism. We demonstrated that nickel complexes with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative addition step, resulting in decarbonylative alkylations, while nickel complexes with monodentate phosphorus ligands promote the activation of the C(acyl)-O bond, leading to the production of ketone products. Although more detailed mechanistic investigations need to be undertaken, the successful development of decarbonylative cross-coupling reactions can serve as a solid foundation for future studies. We believe that this type of decarbonylative cross-coupling reactions will be of significant value, in particularly in combination with the retrosynthetic analysis and synthesis of natural products and biologically active molecules. Thus, the presented ester substitution methods will pave the way for successful applications in the construction of complex frameworks by late-stage modification and functionalization of carboxylic acid derivatives.

  6. Decarbonylative Cross-Couplings: Nickel Catalyzed Functional Group Interconversion Strategies for the Construction of Complex Organic Molecules.

    Guo, Lin; Rueping, Magnus

    2018-05-15

    -mediated decarbonylation process of esters and proposed a reaction mechanism involving a C(acyl)-O bond cleavage and a CO extrusion. Key nickel intermediates were isolated and characterized by Shi and co-workers, supporting the assumption of a nickel/ N-heterocyclic carbene-promoted C(acyl)-O bond activation and functionalization. Our combined experimental and computational study of a ligand-controlled chemoselective nickel-catalyzed cross-coupling of aromatic esters with alkylboron reagents provided further insight into the reaction mechanism. We demonstrated that nickel complexes with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative addition step, resulting in decarbonylative alkylations, while nickel complexes with monodentate phosphorus ligands promote the activation of the C(acyl)-O bond, leading to the production of ketone products. Although more detailed mechanistic investigations need to be undertaken, the successful development of decarbonylative cross-coupling reactions can serve as a solid foundation for future studies. We believe that this type of decarbonylative cross-coupling reactions will be of significant value, in particularly in combination with the retrosynthetic analysis and synthesis of natural products and biologically active molecules. Thus, the presented ester substitution methods will pave the way for successful applications in the construction of complex frameworks by late-stage modification and functionalization of carboxylic acid derivatives.

  7. Decarbonylative Cross-Couplings: Nickel Catalyzed Functional Group Interconversion Strategies for the Construction of Complex Organic Molecules

    Guo, Lin; Rueping, Magnus

    2018-01-01

    -mediated decarbonylation process of esters and proposed a reaction mechanism involving a C(acyl)-O bond cleavage and a CO extrusion. Key nickel intermediates were isolated and characterized by Shi and co-workers, supporting the assumption of a nickel/ N-heterocyclic carbene-promoted C(acyl)-O bond activation and functionalization. Our combined experimental and computational study of a ligand-controlled chemoselective nickel-catalyzed cross-coupling of aromatic esters with alkylboron reagents provided further insight into the reaction mechanism. We demonstrated that nickel complexes with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative addition step, resulting in decarbonylative alkylations, while nickel complexes with monodentate phosphorus ligands promote the activation of the C(acyl)-O bond, leading to the production of ketone products. Although more detailed mechanistic investigations need to be undertaken, the successful development of decarbonylative cross-coupling reactions can serve as a solid foundation for future studies. We believe that this type of decarbonylative cross-coupling reactions will be of significant value, in particularly in combination with the retrosynthetic analysis and synthesis of natural products and biologically active molecules. Thus, the presented ester substitution methods will pave the way for successful applications in the construction of complex frameworks by late-stage modification and functionalization of carboxylic acid derivatives.

  8. Attempts to Synthesize 3-acyl-4-hydroxycoumarins from Meldrum’s acid -- and Related Chemistry

    Ye, Fengbin; Tropp, Kristin; Yu, Yiting

    2007-01-01

    We start our synthetic work with the acylation of Meldrum’s acid to get three different 5-acyl Meldrum’s acids. These compounds are attacked by various nucleophiles containing different hetero atoms to obtain β-ketoesters, β-ketoamides and the corresponding β-keto-phosphorus compounds respectively. New β-ketoamides could be synthesized and characterized. The reaction of acylated Meldrum’s acid and diphenylphosphine did not lead to the expected β-keto-phosphide compound, but the resulting prod...

  9. Exploring Cooperative Effects in Oxidative NHC Catalysis: Regioselective Acylation of Carbohydrates.

    Cramer, David L; Bera, Srikrishna; Studer, Armido

    2016-05-23

    The utility of oxidative NHC catalysis for both the regioselective and chemoselective functionalization of carbohydrates is explored. Chiral NHCs allow for the highly regioselective oxidative esterification of various carbohydrates using aldehydes as acylation precursors. The transformation was also shown to be amenable to both cis/trans diol isomers, free amino groups, and selective for specific sugar epimers in competition experiments. Efficiency and regioselectivity of the acylation can be improved upon using two different NHC catalysts that act cooperatively. The potential of the method is documented by the regioselective acylation of an amino-linked neodisaccharide. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Age-dependent decline in acyl-ghrelin concentrations and reduced association of acyl-ghrelin and growth hormone in healthy older adults.

    Nass, Ralf; Farhy, Leon S; Liu, Jianhua; Pezzoli, Suzan S; Johnson, Michael L; Gaylinn, Bruce D; Thorner, Michael O

    2014-02-01

    Acyl-ghrelin is thought to have both orexigenic effects and to stimulate GH release. A possible cause of the anorexia of aging is an age-dependent decrease in circulating acyl-ghrelin levels. The purpose of the study was to compare acyl-ghrelin and GH concentrations between healthy old and young adults and to examine the relationship of acyl-ghrelin and GH secretion in both age groups. Six healthy older adults (age 62-74 y, body mass index range 20.9-29 kg/m(2)) and eight healthy young men (aged 18-28 y, body mass index range 20.6-26.2 kg/m(2)) had frequent blood samples drawn for hormone measurements every 10 minutes for 24 hours. Ghrelin was measured in an in-house, two-site sandwich ELISA specific for full-length acyl-ghrelin. GH was measured in a sensitive assay (Immulite 2000), and GH peaks were determined by deconvolution analysis. The acyl-ghrelin/GH association was estimated from correlations between amplitudes of individual GH secretory events and the average acyl-ghrelin concentration in the 60-minute interval preceding each GH burst. Twenty-four-hour mean (±SEM) GH (0.48 ± 0.14 vs 2.2 ± 0.3 μg/L, P adults compared with young adults. Twenty-four-hour cortisol concentrations were higher in the old than the young adults (15.1 ± 1.0 vs 10.6 ± 0.9 μg/dL, respectively, P young adults (0.16 ± 0.12 vs 0.69 ± 0.04, P age-dependent decline in circulating acyl-ghrelin levels, which might play a role both in the decline of GH and in the anorexia of aging. Our data also suggest that with normal aging, endogenous acyl-ghrelin levels are less tightly linked to GH regulation.

  11. Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels?

    Özcan, Behiye; Neggers, Sebastian J C M M; Miller, Anne Reifel; Yang, Hsiu-Chiung; Lucaites, Virginia; Abribat, Thierry; Allas, Soraya; Huisman, Martin; Visser, Jenny A; Themmen, Axel P N; Sijbrands, Eric J G; Delhanty, Patric J D; van der Lely, Aart Jan

    2014-06-01

    The objective of this study was to assess the effects of a continuous overnight infusion of des-acyl ghrelin (DAG) on acylated ghrelin (AG) levels and glucose and insulin responses to a standard breakfast meal (SBM) in eight overweight patients with type 2 diabetes. Furthermore, in the same patients and two additional subjects, the effects of DAG infusion on AG concentrations and insulin sensitivity during a hyperinsulinemic-euglycemic clamp (HEC) were assessed. A double-blind, placebo-controlled cross-over study design was implemented, using overnight continuous infusions of 3 and 10  μg DAG/kg per h and placebo to study the effects on a SBM. During a HEC, we studied the insulin sensitivity. We observed that, compared with placebo, overnight DAG administration significantly decreased postprandial glucose levels, both during continuous glucose monitoring and at peak serum glucose levels. The degree of improvement in glycemia was correlated with baseline plasma AG concentrations. Concurrently, DAG infusion significantly decreased fasting and postprandial AG levels. During the HEC, 2.5  h of DAG infusion markedly decreased AG levels, and the M-index, a measure of insulin sensitivity, was significantly improved in the six subjects in whom we were able to attain steady-state euglycemia. DAG administration was not accompanied by many side effects when compared with placebo. DAG administration improves glycemic control in obese subjects with type 2 diabetes through the suppression of AG levels. DAG is a good candidate for the development of compounds in the treatment of metabolic disorders or other conditions with a disturbed AG:DAG ratio, such as type 2 diabetes mellitus or Prader-Willi syndrome. © 2014 European Society of Endocrinology.

  12. Highly efficient extraction and lipase-catalyzed transesterification of triglycerides from Chlorella sp. KR-1 for production of biodiesel.

    Lee, Ok Kyung; Kim, Young Hyun; Na, Jeong-Geol; Oh, You-Kwan; Lee, Eun Yeol

    2013-11-01

    We developed a method for the highly efficient lipid extraction and lipase-catalyzed transesterification of triglyceride from Chlorella sp. KR-1 using dimethyl carbonate (DMC). Almost all of the total lipids, approximately 38.9% (w/w) of microalgae dry weight, were extracted from the dried microalgae biomass using a DMC and methanol mixture (7:3 (v/v)). The extracted triglycerides were transesterified into fatty acid methyl esters (FAMEs) using Novozyme 435 as the biocatalyst in DMC. Herein, DMC was used as the reaction medium and acyl acceptor. The reaction conditions were optimized and the FAMEs yield was 293.82 mg FAMEs/g biomass in 6 h of reaction time at 60 °C in the presence of 0.2% (v/v) water. Novozyme 435 was reused more than ten times while maintaining relative FAMEs conversion that was greater than 90% of the initial FAMEs conversion. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Mechanism of papain-catalyzed synthesis of oligo-tyrosine peptides.

    Mitsuhashi, Jun; Nakayama, Tsutomu; Narai-Kanayama, Asako

    2015-01-01

    Di-, tri-, and tetra-tyrosine peptides with angiotensin I-converting enzyme inhibitory activity were synthesized by papain-catalyzed polymerization of L-tyrosine ethyl ester in aqueous media at 30 °C. Varying the reaction pH from 6.0 to 7.5 and the initial concentration of the ester substrate from 25 to 100 mM, the highest yield of oligo-tyrosine peptides (79% on a substrate basis) was produced at pH 6.5 and 75 mM, respectively. In the reaction initiated with 100 mM of the substrate, approx. 50% yield of insoluble, highly polymerized peptides accumulated. At less than 15 mM, the reaction proceeded poorly; however, from 30 mM to 120 mM a dose-dependent increase in the consumption rate of the substrate was observed with a sigmoidal curve. Meanwhile, each of the tri- and tetra-tyrosine peptides, even at approx. 5mM, was consumed effectively by papain but was not elongated to insoluble polymers. For deacylation of the acyl-papain intermediate through which a new peptide bond is made, L-tyrosine ethyl ester, even at 5mM, showed higher nucleophilic activity than di- and tri-tyrosine. These results indicate that the mechanism through which papain polymerizes L-tyrosine ethyl ester is as follows: the first interaction between papain and the ester substrate is a rate-limiting step; oligo-tyrosine peptides produced early in the reaction period are preferentially used as acyl donors, while the initial ester substrate strongly contributes as a nucleophile to the elongation of the peptide product; and the balance between hydrolytic fragmentation and further elongation of oligo-tyrosine peptides is dependent on the surrounding concentration of the ester substrate. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Pyridine Group-Assisted Addition of Diazo-Compounds to Imines in the 3-CC Reaction of 2-Aminopyridines, Aldehydes, and Diazo-Compounds

    Gulevich, Anton V.; Helan, Victoria; Wink, Donald J.

    2013-01-01

    A novel three-component (3-CC) coupling reaction of 2-aminoazines, aromatic aldehydes and diazo-compounds producing polyfunctional β-amino-α-diazo-compounds has been developed. The reaction features an unprecedented heterocycle-assisted addition of a diazo-compound to an imine. The obtained diazoesters were efficiently converted into valuable heterocycles, as well as to β-amino acid derivatives. PMID:23373731

  15. Syn-Selective Synthesis of β-Branched α-Amino Acids by Alkylation of Glycine-Derived Imines with Secondary Sulfonates.

    Lou, Sha; McKenna, Grace M; Tymonko, Steven A; Ramirez, Antonio; Benkovics, Tamas; Conlon, David A; González-Bobes, Francisco

    2015-10-16

    A syn-selective synthesis of β-branched α-amino acids has been developed based on the alkylation of glycine imine esters with secondary sulfonates. The potassium counterion for the enolate, the solvent, and the leaving group on the electrophile were key levers to maximize the diasteroselectivity of the alkylation. The optimized conditions enabled a straightforward preparation of a number of β-branched α-amino acids that can be challenging to obtain.

  16. Diketones and ketoesters synthesis by acylation of substituted trimethylsilyl lithio-malonates

    Mayani, Mbutyabo

    1983-01-01

    The acylation of trimethylsilyl substituted lithio malonates with dicarbonyl-dichlorides and diacid monoester chlorides gives, after a simple hydrolysis by water, various diketones and ketoesters. The yields are generally good. The method is easy. (author) [fr

  17. Covalent organic polymer functionalization of activated carbon surfaces through acyl chloride for environmental clean-up

    Mines, Paul D.; Thirion, Damien; Uthuppu, Basil

    2017-01-01

    Nanoporous networks of covalent organic polymers (COPs) are successfully grafted on the surfaces of activated carbons, through a series of surface modification techniques, including acyl chloride formation by thionyl chloride. Hybrid composites of activated carbon functionalized with COPs exhibit...

  18. A metalloenzyme-like catalytic system for the chemoselective oxidative cross-coupling of primary amines to imines under ambient conditions.

    Largeron, Martine; Fleury, Maurice-Bernard

    2015-02-23

    The direct oxidative cross-coupling of primary amines is a challenging transformation as homocoupling is usually preferred. We report herein the chemoselective preparation of cross-coupled imines through the synergistic combination of low loadings of Cu(II) metal-catalyst and o-iminoquinone organocatalyst under ambient conditions. This homogeneous cooperative catalytic system has been inspired by the reaction of copper amine oxidases, a family of metalloenzymes with quinone organic cofactors that mediate the selective oxidation of primary amines to aldehydes. After optimization, the desired cross-coupled imines are obtained in high yields with broad substrate scope through a transamination process that leads to the homocoupled imine intermediate, followed by dynamic transimination. The ability to carry out the reactions at room temperature and with ambient air, rather than molecular oxygen as the oxidant, and equimolar amounts of each coupling partner is particularly attractive from an environmentally viewpoint. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Influence of Endo- and Exocyclic Heteroatoms on Stabilities and 1,3-Dipolar Cycloaddition Reactivities of Mesoionic Azomethine Ylides and Imines.

    Champagne, Pier Alexandre; Houk, K N

    2017-10-20

    The geometries, stabilities, and 1,3-dipolar cycloaddition reactivities of 24 mesoionic azomethine ylides and imines were investigated using density functional theory calculations at the M06-2X/6-311+G-(d,p)/M06-2X/6-31G-(d) level. The computed structures highlight how the commonly used "aromatic" resonance form should be replaced by two more accurate resonance structures. Stabilities of the dipoles were assessed by various homodesmotic schemes and are consistent with these compounds being nonaromatic. The activation free energies with ethylene or acetylene range from 11.8 to 36.6 kcal/mol. Within each dipole type, the predicted cycloaddition reactivities correlate with the reaction energies and the resonance stabilization energies provided by the various substituents. Endocyclic (X) heteroatoms increase the reactivity of the 1,3-dipoles in the order of O > NH ≅ S, whereas exocyclic (Y) substituents increase it in the order of CH 2 > NH > O > S. Distortion/interaction analysis indicated that the difference in reactivity between differently substituted 1,3-dipoles is driven by distortion, whereas the difference between azomethine ylides and imines is related to lower interaction energies of imines with the dipolarophiles.

  20. Metabolism of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine in the human neutrophil

    Triggiani, M.; D'Souza, D.M.; Chilton, F.H.

    1991-01-01

    The biosynthesis of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (1-acyl-2-acetyl-GPC) together with that of 1-alkyl-2-acetyl-GPC (platelet-activating factor) has been demonstrated in a variety of inflammatory cells and tissues. It has been hypothesized that the relative proportion of these phospholipids produced upon cell activation may be influenced by their rates of catabolism. We studied the catabolism of 1-acyl-2-acetyl-GPC in resting and activated human neutrophils and compared it to that of 1-alkyl-2-acetyl-GPC. Neutrophils rapidly catabolize both 1-alkyl-2-acetyl-GPC and 1-acyl-2-acetyl-GPC; however, the rate of catabolism of 1-acyl-2-acetyl-GPC is approximately 2-fold higher than that of 1-alkyl-2-acetyl-GPC. In addition, most of 1-acyl-2-acetyl-GPC is catabolized through a pathway different from that of 1-alkyl-2-acetyl-GPC. The main step in the catabolism of 1-acyl-2-acetyl-GPC is the removal of the long chain at the sn-1 position; the long chain residue is subsequently incorporated either into triglycerides or into phosphatidylcholine. The 1-lyso-2-acetyl-GPC formed in this reaction is then further degraded to glycerophosphocholine, choline, or phosphocholine. 1-Acyl-2-acetyl-GPC is also catabolized, to a lesser extent, through deacetylation at the sn-2 position and reacylation with a long chain fatty acid. Stimulation of neutrophils by A23187 results in a higher rate of catabolism of 1-acyl-2-acetyl-GPC by increasing both the removal of the long chain at the sn-1 position and the deacetylation-reacylation at the sn-2 position. In a broken cell preparation, the cytosolic fraction of the neutrophil was shown to contain an enzyme activity which cleaved the sn-1 position of 1-acyl-2-acetyl-GPC and 1-acyl-2-lyso-GPC but not of 1,2-diacyl-GPC

  1. A liver-specific defect of Acyl-CoA degradation produces hyperammonemia, hypoglycemia and a distinct hepatic Acyl-CoA pattern.

    Nicolas Gauthier

    Full Text Available Most conditions detected by expanded newborn screening result from deficiency of one of the enzymes that degrade acyl-coenzyme A (CoA esters in mitochondria. The role of acyl-CoAs in the pathophysiology of these disorders is poorly understood, in part because CoA esters are intracellular and samples are not generally available from human patients. We created a mouse model of one such condition, deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase (HL, in liver (HLLKO mice. HL catalyses a reaction of ketone body synthesis and of leucine degradation. Chronic HL deficiency and acute crises each produced distinct abnormal liver acyl-CoA patterns, which would not be predictable from levels of urine organic acids and plasma acylcarnitines. In HLLKO hepatocytes, ketogenesis was undetectable. Carboxylation of [2-(14C] pyruvate diminished following incubation of HLLKO hepatocytes with the leucine metabolite 2-ketoisocaproate (KIC. HLLKO mice also had suppression of the normal hyperglycemic response to a systemic pyruvate load, a measure of gluconeogenesis. Hyperammonemia and hypoglycemia, cardinal features of many inborn errors of acyl-CoA metabolism, occurred spontaneously in some HLLKO mice and were inducible by administering KIC. KIC loading also increased levels of several leucine-related acyl-CoAs and reduced acetyl-CoA levels. Ultrastructurally, hepatocyte mitochondria of KIC-treated HLLKO mice show marked swelling. KIC-induced hyperammonemia improved following administration of carglumate (N-carbamyl-L-glutamic acid, which substitutes for the product of an acetyl-CoA-dependent reaction essential for urea cycle function, demonstrating an acyl-CoA-related mechanism for this complication.

  2. Acyl carrier proteins from sunflower (Helianthus annuus L.) seeds and their influence on FatA and FatB acyl-ACP thioesterase activities.

    Aznar-Moreno, Jose A; Venegas-Calerón, Mónica; Martínez-Force, Enrique; Garcés, Rafael; Salas, Joaquín J

    2016-08-01

    The kinetics of acyl-ACP thioesterases from sunflower importantly changed when endogenous ACPs were used. Sunflower FatB was much more specific towards saturated acyl-ACPs when assayed with them. Acyl carrier proteins (ACPs) are small (~9 kDa), soluble, acidic proteins involved in fatty acid synthesis in plants and bacteria. ACPs bind to fatty acids through a thioester bond, generating the acyl-ACP lipoproteins that are substrates for fatty acid synthase (FAS) complexes, and that are required for fatty acid chain elongation, acting as important intermediates in de novo fatty acid synthesis in plants. Plants, usually express several ACP isoforms with distinct functionalities. We report here the cloning of three ACPs from developing sunflower seeds: HaACP1, HaACP2, and HaACP3. These proteins were plastidial ACPs expressed strongly in seeds, and as such they are probably involved in the synthesis of sunflower oil. The recombinant sunflower ACPs were expressed in bacteria but they were lethal to the prokaryote host. Thus, they were finally produced using the GST gene fusion system, which allowed the apo-enzyme to be produced and later activated to the holo form. Radiolabelled acyl-ACPs from the newly cloned holo-ACP forms were also synthesized and used to characterize the activity of recombinant sunflower FatA and FatB thioesterases, important enzymes in plant fatty acids synthesis. The activity of these enzymes changed significantly when the endogenous ACPs were used. Thus, FatA importantly increased its activity levels, whereas FatB displayed a different specificity profile, with much high activity levels towards saturated acyl-CoA derivatives. All these data pointed to an important influence of the ACP moieties on the activity of enzymes involved in lipid synthesis.

  3. Acyl Meldrum's acid derivatives: application in organic synthesis

    Janikowska, K; Rachoń, J; Makowiec, S

    2014-01-01

    This review is focused on an important class of Meldrum's acid derivatives commonly known as acyl Meldrum's acids. The preparation methods of these compounds are considered including the recently proposed and rather rarely used ones. The chemical properties of acyl Meldrum's acids are described in detail, including thermal stability and reactions with various nucleophiles. The possible mechanisms of these transformations are analyzed. The bibliography includes 134 references

  4. Mild and Highly Efficient Copper(I Inspired Acylation of Alcohols and Polyols

    Enoch A. Mensah

    2017-01-01

    Full Text Available A new and highly efficient method mediated by tetrakis(acetonitrilecopper(I triflate for activating both simple and highly hindered anhydrides in the acylation of alcohols and polyols is described. This new acylation method is mild and mostly proceeds at room temperature with low catalyst loading. The method is versatile and has been extended to a wide variety of different alcohol substrates to afford the corresponding ester products in good to excellent yields.

  5. Deciphering the acylation pattern of Yersinia enterocolitica lipid A.

    Mar Reinés

    Full Text Available Pathogenic bacteria may modify their surface to evade the host innate immune response. Yersinia enterocolitica modulates its lipopolysaccharide (LPS lipid A structure, and the key regulatory signal is temperature. At 21°C, lipid A is hexa-acylated and may be modified with aminoarabinose or palmitate. At 37°C, Y. enterocolitica expresses a tetra-acylated lipid A consistent with the 3'-O-deacylation of the molecule. In this work, by combining genetic and mass spectrometric analysis, we establish that Y. enterocolitica encodes a lipid A deacylase, LpxR, responsible for the lipid A structure observed at 37°C. Western blot analyses indicate that LpxR exhibits latency at 21°C, deacylation of lipid A is not observed despite the expression of LpxR in the membrane. Aminoarabinose-modified lipid A is involved in the latency. 3-D modelling, docking and site-directed mutagenesis experiments showed that LpxR D31 reduces the active site cavity volume so that aminoarabinose containing Kdo(2-lipid A cannot be accommodated and, therefore, not deacylated. Our data revealed that the expression of lpxR is negatively controlled by RovA and PhoPQ which are necessary for the lipid A modification with aminoarabinose. Next, we investigated the role of lipid A structural plasticity conferred by LpxR on the expression/function of Y. enterocolitica virulence factors. We present evidence that motility and invasion of eukaryotic cells were reduced in the lpxR mutant grown at 21°C. Mechanistically, our data revealed that the expressions of flhDC and rovA, regulators controlling the flagellar regulon and invasin respectively, were down-regulated in the mutant. In contrast, the levels of the virulence plasmid (pYV-encoded virulence factors Yops and YadA were not affected in the lpxR mutant. Finally, we establish that the low inflammatory response associated to Y. enterocolitica infections is the sum of the anti-inflammatory action exerted by pYV-encoded YopP and the

  6. Deciphering the acylation pattern of Yersinia enterocolitica lipid A.

    Reinés, Mar; Llobet, Enrique; Dahlström, Käthe M; Pérez-Gutiérrez, Camino; Llompart, Catalina M; Torrecabota, Nuria; Salminen, Tiina A; Bengoechea, José A

    2012-01-01

    Pathogenic bacteria may modify their surface to evade the host innate immune response. Yersinia enterocolitica modulates its lipopolysaccharide (LPS) lipid A structure, and the key regulatory signal is temperature. At 21°C, lipid A is hexa-acylated and may be modified with aminoarabinose or palmitate. At 37°C, Y. enterocolitica expresses a tetra-acylated lipid A consistent with the 3'-O-deacylation of the molecule. In this work, by combining genetic and mass spectrometric analysis, we establish that Y. enterocolitica encodes a lipid A deacylase, LpxR, responsible for the lipid A structure observed at 37°C. Western blot analyses indicate that LpxR exhibits latency at 21°C, deacylation of lipid A is not observed despite the expression of LpxR in the membrane. Aminoarabinose-modified lipid A is involved in the latency. 3-D modelling, docking and site-directed mutagenesis experiments showed that LpxR D31 reduces the active site cavity volume so that aminoarabinose containing Kdo(2)-lipid A cannot be accommodated and, therefore, not deacylated. Our data revealed that the expression of lpxR is negatively controlled by RovA and PhoPQ which are necessary for the lipid A modification with aminoarabinose. Next, we investigated the role of lipid A structural plasticity conferred by LpxR on the expression/function of Y. enterocolitica virulence factors. We present evidence that motility and invasion of eukaryotic cells were reduced in the lpxR mutant grown at 21°C. Mechanistically, our data revealed that the expressions of flhDC and rovA, regulators controlling the flagellar regulon and invasin respectively, were down-regulated in the mutant. In contrast, the levels of the virulence plasmid (pYV)-encoded virulence factors Yops and YadA were not affected in the lpxR mutant. Finally, we establish that the low inflammatory response associated to Y. enterocolitica infections is the sum of the anti-inflammatory action exerted by pYV-encoded YopP and the reduced activation of

  7. Plant fatty acyl reductases: enzymes generating fatty alcohols for protective layers with potential for industrial applications.

    Rowland, Owen; Domergue, Frédéric

    2012-09-01

    Primary fatty alcohols are found throughout the biological world, either in free form or in a combined state. They are common components of plant surface lipids (i.e. cutin, suberin, sporopollenin, and associated waxes) and their absence can significantly perturb these essential barriers. Fatty alcohols and/or derived compounds are also likely to have direct functions in plant biotic and abiotic interactions. An evolutionarily related set of alcohol-forming fatty acyl reductases (FARs) is present in all kingdoms of life. Plant microsomal and plastid-associated FAR enzymes have been characterized, acting on acyl-coenzymeA (acyl-CoA) or acyl-acyl carrier protein (acyl-ACP) substrates, respectively. FARs have distinct substrate specificities both with regard to chain length and chain saturation. Fatty alcohols and wax esters, which are a combination of fatty alcohol and fatty acid, have a variety of commercial applications. The expression of FARs with desired specificities in transgenic microbes or oilseed crops would provide a novel means of obtaining these valuable compounds. In the present review, we report on recent progress in characterizing plant FAR enzymes and in understanding the biological roles of primary fatty alcohols, as well as describe the biotechnological production and industrial uses of fatty alcohols. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Acyl transfer from membrane lipids to peptides is a generic process.

    Dods, Robert H; Bechinger, Burkhard; Mosely, Jackie A; Sanderson, John M

    2013-11-15

    The generality of acyl transfer from phospholipids to membrane-active peptides has been probed using liquid chromatography-mass spectrometry analysis of peptide-lipid mixtures. The peptides examined include melittin, magainin II, PGLa, LAK1, LAK3 and penetratin. Peptides were added to liposomes with membrane lipid compositions ranging from pure phosphatidylcholine (PC) to mixtures of PC with phosphatidylethanolamine, phosphatidylserine or phosphatidylglycerol. Experiments were typically conducted at pH7.4 at modest salt concentrations (90 mM NaCl). In favorable cases, lipidated peptides were further characterized by tandem mass spectrometry methods to determine the sites of acylation. Melittin and magainin II were the most reactive peptides, with significant acyl transfer detected under all conditions and membrane compositions. Both peptides were lipidated at the N-terminus by transfer from PC, phosphatidylethanolamine, phosphatidylserine or phosphatidylglycerol, as well as at internal sites: lysine for melittin; serine and lysine for magainin II. Acyl transfer could be detected within 3h of melittin addition to negatively charged membranes. The other peptides were less reactive, but for each peptide, acylation was found to occur in at least one of the conditions examined. The data demonstrate that acyl transfer is a generic process for peptides bound to membranes composed of diacylglycerophospholipids. Phospholipid membranes cannot therefore be considered as chemically inert toward peptides and by extension proteins. © 2013. Published by Elsevier Ltd. All rights reserved.

  9. Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord

    Sato, Miho; Nakahara, Keiko; Goto, Shintaro; Kaiya, Hiroyuki; Miyazato, Mikiya; Date, Yukari; Nakazato, Masamitsu; Kangawa, Kenji; Murakami, Noboru

    2006-01-01

    Expressions of the growth hormone secretagogue receptor (GHS-R) mRNA and its protein were confirmed in rat fetal spinal cord tissues by RT-PCR and immunohistochemistry. In vitro, over 3 nM ghrelin and des-acyl ghrelin induced significant proliferation of primary cultured cells from the fetal spinal cord. The proliferating cells were then double-stained using antibodies against the neuronal precursor marker, nestin, and the cell proliferation marker, 5-bromo-2'-deoxyuridine (BrdU), and the nestin-positive cells were also found to be co-stained with antibody against GHS-R. Furthermore, binding studies using [ 125 I]des-acyl ghrelin indicated the presence of a specific binding site for des-acyl ghrelin, and confirmed that the binding was displaced with unlabeled des-acyl ghrelin or ghrelin. These results indicate that ghrelin and des-acyl ghrelin induce proliferation of neuronal precursor cells that is both dependent and independent of GHS-R, suggesting that both ghrelin and des-acyl ghrelin are involved in neurogenesis of the fetal spinal cord

  10. Lipopolysaccharides with acylation defects potentiate TLR4 signaling and shape T cell responses.

    Anna Martirosyan

    Full Text Available Lipopolysaccharides or endotoxins are components of Gram-negative enterobacteria that cause septic shock in mammals. However, a LPS carrying hexa-acyl lipid A moieties is highly endotoxic compared to a tetra-acyl LPS and the latter has been considered as an antagonist of hexa-acyl LPS-mediated TLR4 signaling. We investigated the relationship between the structure and the function of bacterial LPS in the context of human and mouse dendritic cell activation. Strikingly, LPS with acylation defects were capable of triggering a strong and early TLR4-dependent DC activation, which in turn led to the activation of the proteasome machinery dampening the pro-inflammatory cytokine secretion. Upon activation with tetra-acyl LPS both mouse and human dendritic cells triggered CD4(+ T and CD8(+ T cell responses and, importantly, human myeloid dendritic cells favored the induction of regulatory T cells. Altogether, our data suggest that LPS acylation controlled by pathogenic bacteria might be an important strategy to subvert adaptive immunity.

  11. Plasma levels of acylated and total ghrelin in pediatric patients with chronic kidney disease.

    Naufel, Maria Fernanda Soares; Bordon, Milena; de Aquino, Talita Marques; Ribeiro, Eliane Beraldi; de Abreu Carvalhaes, João Tomás

    2010-12-01

    This cross-sectional study set out to compare total and acyl ghrelin levels in children with mild chronic kidney disease (CKD) undergoing conservative treatment (n = 19) with children with end-stage renal disease (ESRD) undergoing hemodialysis (n = 24), and with healthy controls (n = 20). The relationship between ghrelin levels and parameters of renal function, nutritional status, and selective hormones were investigated. ESRD patients had higher total ghrelin levels than those with mild CKD or control individuals. However, acyl ghrelin did not differ between groups, indicating that the excess circulating ghrelin was desacylated. Since desacyl ghrelin has been shown to inhibit appetite, increased levels might contribute to protein-energy wasting in pediatric renal patients. When all 43 renal patients were combined, multiple regression analysis found age and glomerular filtration rate (GFR) to be significant negative predictors of total ghrelin. Acyl ghrelin was influenced negatively by age and positively by energy intake. Acyl to total ghrelin ratio related positively to GFR and energy intake. The results indicate that total but not acyl ghrelin is influenced by low GFR in children with CKD and suggests that ghrelin activation may be impaired in these patients. Since energy intake is a positive predictor of acyl ghrelin, the physiological control of ghrelin secretion appears to be altered in pediatric renal patients.

  12. Poly(vinyl-alcohol)/poly(ethylene-glycol)/poly(ethylene-imine) blend membranes - structure and CO2 facilitated transport

    Ben Hamouda, S.; Quang, Trong Nguyen; Langevin, D.; Sadok, Roudeslic

    2010-01-01

    Poly(vinyl-alcohol) (PVA)/poly(ethylene-imine) (PEI)/poly(ethylene-glycol) (PEG) blend membranes were prepared by solution casting followed by solvent evaporation. The effects of the blend polymer composition on the membrane structure and CO 2 /N 2 permeation characteristics were investigated. IR spectroscopy evidenced strong hydrogen bonding interactions between amorphous PVA and PEI, and weaker interactions between PVA and PEG. DSC studies showed that PVA crystallization was partially inhibited by the interactions between amorphous PVA and PEI blend, in which PEG separated into nodules. The CO 2 permeability decreased with an increase in CO 2 partial pressure in feed gas, while the N 2 permeability remained constant. This result indicated that only CO 2 was transported by the facilitated transport mechanism. The CO 2 and N 2 permeabilities increased monotonically with the PEI content in the blend membranes, whereas the ideal selectivity of CO 2 to N 2 transport showed a maximum. When CO 2 is humidified, its permeability through the blend membranes is much higher than that of dry CO 2 , but the change in permeability due to the presence of humidity is reversible. (authors)

  13. Photometric Characterization of the Reductive Amination Scope of the Imine Reductases from Streptomyces tsukubaensis and Streptomyces ipomoeae.

    Matzel, Philipp; Krautschick, Lukas; Höhne, Matthias

    2017-10-18

    Imine reductases (IREDs) have emerged as promising enzymes for the asymmetric synthesis of secondary and tertiary amines starting from carbonyl substrates. Screening the substrate specificity of the reductive amination reaction is usually performed by time-consuming GC analytics. We found two highly active IREDs in our enzyme collection, IR-20 from Streptomyces tsukubaensis and IR-Sip from Streptomyces ipomoeae, that allowed a comprehensive substrate screening with a photometric NADPH assay. We screened 39 carbonyl substrates combined with 17 amines as nucleophiles. Activity data from 663 combinations provided a clear picture about substrate specificity and capabilities in the reductive amination of these enzymes. Besides aliphatic aldehydes, the IREDs accepted various cyclic (C 4 -C 8 ) and acyclic ketones, preferentially with methylamine. IR-Sip also accepted a range of primary and secondary amines as nucleophiles. In biocatalytic reactions, IR-Sip converted (R)-3-methylcyclohexanone with dimethylamine or pyrrolidine with high diastereoselectivity (>94-96 % de). The nucleophile acceptor spectrum depended on the carbonyl substrate employed. The conversion of well-accepted substrates could also be detected if crude lysates were employed as the enzyme source. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Effect of the shell on the transport properties of poly(glycerol) and Poly(ethylene imine) nanoparticles

    Adeli, M.; Haag, R.; Zarnegar, Z.

    2007-01-01

    Dendritic core-shell architectures containing poly (glycerol) and poly (ethylene imine) cores and poly(lactide) shell (PG-PLA and PEI-PLA respectively) were synthesized. Analogous of these core-shell architectures containing the same cores but poly (L-lactide) shell (PG-PLLA and PEI-PLLA, respectively) were also synthesized. In this work PG and PEI were used as macroinitiator for ring opening polymerization of the lactid and L-lactide monomers. Different molar ratios of monomer to end functional groups of PG ([LA]/[OH]) and PEI ([LA]/[NHn] (n = 1 or 2)) were used to prepare the core-shell architectures with different shell thickness. These core-shell architectures were able to encapsulate and transport the small guest molecules. Their transport capacity (TC) depended on the type and thickness of the shells. TC of core-shell architectures containing PLLA shell was higher than that for their analogs containing PLA shell. The diameter of core-shell architectures was between 20-80 nm. The rate of release of guest molecules from chloroform solution of nanocarriers to water phase was investigated and it depended on the type of the core, shell and solvent

  15. Zeolite 5A Catalyzed Etherification of Diphenylmethanol

    Cooke, Jason; Henderson, Eric J.; Lightbody, Owen C.

    2009-01-01

    An experiment for the synthetic undergraduate laboratory is described in which zeolite 5A catalyzes the room temperature dehydration of diphenylmethanol, (C[subscript 6]H[subscript 5])[subscript 2]CHOH, producing 1,1,1',1'-tetraphenyldimethyl ether, (C[subscript 6]H[subscript 5])[subscript 2]CHOCH(C[subscript 6]H[subscript 5])[subscript 2]. The…

  16. Muon catalyzed fusion under compressive conditions

    Cripps, G.; Goel, B.; Harms, A.A.

    1991-01-01

    The viability of a symbiotic combination of Muon Catalyzed Fusion (μCF) and high density generation processes has been investigated. The muon catalyzed fusion reaction rates are formulated in the temperature and density range found under moderate compressive conditions. Simplified energy gain and power balance calculations indicate that significant energy gain occurs only if standard type deuterium-tritium (dt) fusion is ignited. A computer simulation of the hydrodynamics and fusion kinetics of a spherical deuterium-tritium pellet implosion including muons is performed. Using the muon catalyzed fusion reaction rates formulated and under ideal conditions, the pellet ignites (and thus has a significant energy gain) only if the initial muon concentration is approximately 10 17 cm -3 . The muons need to be delivered to the pellet within a very short-time (≅ 1 ns). The muon pulse required in order to make the high density and temperature muon catalyzed fusion scheme viable is beyond the present technology for muon production. (orig.) [de

  17. Enyne Metathesis Catalyzed by Ruthenium Carbene Complexes

    Poulsen, Carina Storm; Madsen, Robert

    2003-01-01

    Enyne metathesis combines an alkene and an alkyne into a 1,3-diene. The first enyne metathesis reaction catalyzed by a ruthenium carbene complex was reported in 1994. This review covers the advances in this transformation during the last eight years with particular emphasis on methodology...

  18. Enzyme-Catalyzed Transetherification of Alkoxysilanes

    Peter G. Taylor

    2013-01-01

    Full Text Available We report the first evidence of an enzyme-catalyzed transetherification of model alkoxysilanes. During an extensive enzymatic screening in the search for new biocatalysts for silicon-oxygen bond formation, we found that certain enzymes promoted the transetherification of alkoxysilanes when tert-butanol or 1-octanol were used as the reaction solvents.

  19. Biodiesel production by enzyme-catalyzed transesterification

    Stamenković Olivera S.

    2005-01-01

    Full Text Available The principles and kinetics of biodiesel production from vegetable oils using lipase-catalyzed transesterification are reviewed. The most important operating factors affecting the reaction and the yield of alkyl esters, such as: the type and form of lipase, the type of alcohol, the presence of organic solvents, the content of water in the oil, temperature and the presence of glycerol are discussed. In order to estimate the prospects of lipase-catalyzed transesterification for industrial application, the factors which influence the kinetics of chemically-catalysed transesterification are also considered. The advantages of lipase-catalyzed transesterification compared to the chemically-catalysed reaction, are pointed out. The cost of down-processing and ecological problems are significantly reduced by applying lipases. It was also emphasized that lipase-catalysed transesterification should be greatly improved in order to make it commercially applicable. The further optimization of lipase-catalyzed transesterification should include studies on the development of new reactor systems with immobilized biocatalysts and the addition of alcohol in several portions, and the use of extra cellular lipases tolerant to organic solvents, intracellular lipases (i.e. whole microbial cells and genetically-modified microorganisms ("intelligent" yeasts.

  20. Defluoridation potential of jute fibers grafted with fatty acyl chain

    Manna, Suvendu; Saha, Prosenjit; Roy, Debasis; Sen, Ramkrishna; Adhikari, Basudam

    2015-11-01

    Waterborne fluoride is usually removed from water by coagulation, adsorption, ion exchange, electro dialysis or reverse osmosis. These processes are often effective over narrow pH ranges, release ions considered hazardous to human health or produce large volumes of toxic sludge that are difficult to handle and dispose. Although plant matters have been shown to remove waterborne fluoride, they suffer from poor removal efficiency. Following from the insight that interaction between microbial carbohydrate biopolymers and anionic surfaces is often facilitated by lipids, an attempt has been made to enhance fluoride adsorption efficiency of jute by grafting the lignocellulosic fiber with fatty acyl chains found in vegetable oils. Fluoride removal efficiency of grafted jute was found to be comparable or higher than those of alternative defluoridation processes. Infrared and X-ray photoelectron spectroscopic evidence indicated that hydrogen bonding, protonation and C-F bonding were responsible for fluoride accumulation on grafted jute. Adsorption based on grafted jute fibers appears to be an economical, sustainable and eco-friendly alternative technique for removing waterborne fluoride.

  1. New acylated flavonoid glycosides from flowers of Aerva javanica.

    Mussadiq, Sara; Riaz, Naheed; Saleem, Muhammad; Ashraf, Muhammad; Ismail, Tayaba; Jabbar, Abdul

    2013-07-01

    Chromatographic purification of ethyl acetate soluble fraction of the methanolic extract of the flowers of Aerva javanica yielded three new acylated flavone glycosides: kaempferol-3-O-β-d-[4‴-E-p-coumaroyl-α-l-rhamnosyl(1 → 6)]-galactoside (1), kaempferol-3-O-β-d-[4‴-E-p-coumaroyl-α-l-rhamnosyl(1 → 6)]-(3″-E-p-coumaroyl)galactoside (2), and kaempferol-3-O-β-d-[4‴-E-p-coumaroyl-α-l-rhamnosyl(1 → 6)]-(4″-E-p-coumaroyl)galactoside (3), along with p-coumaric acid (4), caffeic acid (5), gallic acid (6), eicosanyl-trans-p-coumarate (7), hexadecyl ferulate (8), and hexacosyl ferulate (9). The compounds 1-9 were characterized using 1D ((1)H, (13)C) and 2D NMR (HMQC, HMBC, and COSY) spectroscopy and mass spectrometry (EI-MS, HR-EI-MS, FAB-MS, and HR-FAB-MS) and in comparison with the reported data in the literature. Compound 1 showed weak inhibitory activity against enzymes, such as acetylcholinesterase, butyrylcholinesterase, and lipoxygenase with IC50 values 205.1, 304.1, and 212.3 μM, respectively, whereas compounds 2 and 3 were only weakly active against the enzyme acetylcholinesterase.

  2. Fractionation and Characterization of Tannin Acyl Hydrolase from Aspergillus niger

    YUNITA ARIAN SANI ANWAR

    2009-09-01

    Full Text Available We previously produced tannin acyl hydrolase (tannase from Aspergillus niger isolated from cacao pod. In the present study the enzyme was subjected to fractionation by ammonium sulphate followed by dialysis process. The saturation level of ammonium sulphate used was 30-80% where the best enzyme activity was obtained at the saturation level of 60%. Compared to that of crude enzyme, specific activity of tannase after dialysis was four folds. Characterization results showed that optimum activity was at 35-50 oC and pH 6. Tannase was activated by K+ and Na+ at concentration of 0.01 and 0.05 M respectively. Mg2+ was found activate tannase only at 0.01 M. Addition of metal ions like Zn2+, Cu2+, Ca2+, Mn2+ and Fe2+ inhibited the enzyme activity. Kinetics analysis of various substrates tested showed that the Km value of tannic acid and gallotannin was 0.401 and 6.611 mM respectively. Vmax value of tannic acid was 10.804 U/ml and of gallotannin was 12.406 U/ml. Based on Michaelis-Menten constant (Km, the tannase obtained in the present study was more active in hydrolysing depside bonds rather than ester bonds.

  3. Fractionation and Characterization of Tannin Acyl Hydrolase from Aspergillus niger

    YUNITA ARIAN SANI ANWAR

    2009-09-01

    Full Text Available We previously produced tannin acyl hydrolase (tannase from Aspergillus niger isolated from cacao pod. In the present study the enzyme was subjected to fractionation by ammonium sulphate followed by dialysis process. The saturation level of ammonium sulphate used was 30–80% where the best enzyme activity was obtained at the saturation level of 60%. Compared to that of crude enzyme, specific activity of tannase after dialysis was four folds. Characterization results showed that optimum activity was at 35–50 °C and pH 6. Tannase was activated by K+ and Na+ at concentration of 0.01 and 0.05 M respectively. Mg2+ was found activate tannase only at 0.01 M. Addition of metal ions like Zn2+, Cu2+, Ca2+, Mn2+ and Fe2+ inhibited the enzyme activity. Kinetics analysis of various substrates tested showed that the Km value of tannic acid and gallotannin was 0.401 and 6.611 mM respectively. Vmax value of tannic acid was 10.804 U/ml and of gallotannin was 12.406 U/ml. Based on Michaelis-Menten constant (Km, the tannase obtained in the present study was more active in hydrolysing depside bonds rather than ester bonds.

  4. Acylation and metabolism of (n-6) fatty acids in hepatocytes

    Voss, A.C.; Sprecher, H.

    1986-01-01

    Isolated hepatocytes (5 x 10 6 in 2ml) from chow fed rats were incubated from 20 to 60 min. with increasing concentrations of [1- 14 C] labeled 18:2 (n-6), 18:3 (n-6) or 20:3 (n-6) to define optimum conditions for measuring acylation and metabolism to other (n-6) acids with subsequent incorporation into lipids. The triglycerides (TG) and phospholipids (PL) contained 157 and 80 nmols of 18:2 (n-6) and 6.0 and 6.1 nmols of other (n-6) acids, respectively, when cells were incubated with 0.3mM [1- 14 C] 18:2 (n-6) for 40 min. When cells were incubated with 0.3mM [1- 14 C] 18:2 (n-6) plus 0.15 to 0.45mM 18:3 (n-6) or 20:3 (n-6), the metabolism of 18:2 (n-6) to other (n-6) acids was inhibited but not totally abolished. These results may suggest that (n-6) acid made from linoleate do not totally equilibrate with exogenous 18:3 (n-6) or 20:3

  5. Acylated flavonol tri- and tetraglycosides in the flavonoid metabolome of Cladrastis kentukea (Leguminosae).

    Kite, Geoffrey C; Rowe, Emily R; Lewis, Gwilym P; Veitch, Nigel C

    2011-04-01

    The foliar metabolome of Cladrastis kentukea (Leguminosae) contains a complex mixture of flavonoids including acylated derivatives of the 3-O-rhamnosyl(1→2)[rhamnosyl(1→6)]-galactosides of kaempferol and quercetin and their 7-O-rhamnosides, together with an array of non-acylated kaempferol and quercetin di-, tri- and tetraglycosides. Thirteen of the acylated flavonoids, 12 of which had not been reported previously, were characterised by spectroscopic and chemical methods. Eight of these were the four isomers of kaempferol 3-O-α-l-rhamnopyranosyl(1→2)[α-l-rhamnopyranosyl(1→6)]-(3/4-O-E/Z-p-coumaroyl-β-d-galactopyranoside) and their 7-O-α-l-rhamnopyranosides, and three were isomers of quercetin 3-O-α-l-rhamnopyranosyl(1→2)[α-l-rhamnopyranosyl(1→6)]-(3/4-O-E/Z-p-coumaroyl-β-d-galactopyranoside) - the remaining 4Z isomer was identified by LC-UV-MS analysis of a crude extract. The final two acylated flavonoids characterised by NMR were the 3E and 4E isomers of kaempferol 3-O-α-l-rhamnopyranosyl(1→2)[α-l-rhamnopyranosyl(1→6)]-(3/4-O-E-feruloyl-β-d-galactopyranoside)-7-O-α-l-rhamnopyranoside while the 3Z and 4Z isomers were again detected by LC-UV-MS. Using the observed fragmentation behaviour of the isolated compounds following a variety of MS experiments, a further 18 acylated flavonoids were given tentative structures by LC-MS analysis of a crude extract. Acylated flavonoids were absent from the flowers of C. kentukea, which contained an array of non-acylated kaempferol and quercetin glycosides. Immature fruits contained kaempferol 3-O-α-rhamnopyranosyl(1→2)[α-rhamnopyranosyl(1→6)]-β-galactopyranoside and its 7-O-α-rhamnopyranoside as the major flavonoids with acylated flavonoids, different from those in the leaves, only present as minor constituents. The presence of acylated flavonoids distinguishes the foliar flavonoid metabolome of C. kentukea from that of a closely related legume, Styphnolobium japonicum, which contains a similar

  6. Kinetics of aggregation growth with competition between catalyzed birth and catalyzed death

    Wang Haifeng; Gao Yan; Lin Zhenquan

    2008-01-01

    An aggregation growth model of three species A, B and C with the competition between catalyzed birth and catalyzed death is proposed. Irreversible aggregation occurs between any two aggregates of the like species with the constant rate kernels I n (n = 1,2,3). Meanwhile, a monomer birth of an A species aggregate of size k occurs under the catalysis of a B species aggregate of size j with the catalyzed birth rate kernel K(k,j) = Kkj v and a monomer death of an A species aggregate of size k occurs under the catalysis of a C species aggregate of size j with the catalyzed death rate kernel L(k,j)=Lkj v , where v is a parameter reflecting the dependence of the catalysis reaction rates of birth and death on the size of catalyst aggregate. The kinetic evolution behaviours of the three species are investigated by the rate equation approach based on the mean-field theory. The form of the aggregate size distribution of A species a k (t) is found to be dependent crucially on the competition between the catalyzed birth and death of A species, as well as the irreversible aggregation processes of the three species: (1) In the v k (t) satisfies the conventional scaling form; (2) In the v ≥ 0 case, the competition between the catalyzed birth and death dominates the process. When the catalyzed birth controls the process, a k (t) takes the conventional or generalized scaling form. While the catalyzed death controls the process, the scaling description of the aggregate size distribution breaks down completely

  7. Biosynthesis of plasmalogens by the microsomal fraction of Fischer R-3259 sarcoma. Influence of specific 2-acyl chains on the desaturation of 1-alkyl-2-acyl-sn-gycero-3-phosphoethanolamine

    Wykle, R.L.; Schremmer, J.M.

    1979-08-07

    In the Fischer R-3259 sarcoma, ethanolamine plasmalogens are synthesized from 1-akyl-2-acyl-sn-glycero-3-phosphoethanolamine by a microsomal desaturase that inserts a ..delta../sup 1/ double bond in the alkyl chain. In the present study, a series of 1-(1-/sup 14/C)hexadecyl-2-acyl-GPE substrates containing specific acyl groups ranging from C/sub 2/ /sub 0/ to C/sub 20/ /sub 4/ at the 2 position were prepared and tested as substrates for the microsomal ..delta../sup 1/-alkyl desaturase. The microsomal preparations contained an acyl hydrolase that removed the C/sub 2/ /sub 0/, C/sub 4/ /sub 0/, and C/sub 7/ /sub 0/ acyl groups from the 2 position. By inhibiting the hydrolase with diisopropyl fluorophosphate, it was possible to test conversion of the unaltered substrates to plasmalogens. The alkyl desaturase exhibited little discrimination among the specific acyl derivatives tested. The highest rate of desaturation was obtained with 1-(1-/sup 14/C)-hexadecyl-2-acyl-GPE synthesized in situ in the microsomes via acylation of 1-(1-/sup 14/C)hexadecyl-GPE; this rate was threefold that observed with exogenously acylated substrates. The 1-(1-/sup 14/C)hexadecyl-2-acyl-GPE synthesized in situ contained highly unsaturated acyl groups; no selectivity of the desaturase for specific acyl chains was detected when the different molecular species of 1-(1-/sup 14/C)alkyl-2-acyl-GPE and 1-(1-/sup 14/C)alk-1'-eyl-2-acyl-GPE were compared. The short-chain substrates, being moe hydrophilic, mimicked the chromatographic behavior of 1-alkyl-GPE, yet they did not resemble the lyso compound in its higher conversion to plasmalogens. Thus, despite their similar R/sub f/ values, the packing of the short-chain acyl homologues in the membrane may be quite different from that of the lyso compound. Binding of 1-hexadecyl-2-acyl-GPE and 1-hexadecyl-GPE to microsomal membranes was similar.

  8. Insight into Coenzyme A cofactor binding and the mechanism of acyl-transfer in an acylating aldehyde dehydrogenase from Clostridium phytofermentans.

    Tuck, Laura R; Altenbach, Kirsten; Ang, Thiau Fu; Crawshaw, Adam D; Campopiano, Dominic J; Clarke, David J; Marles-Wright, Jon

    2016-02-22

    The breakdown of fucose and rhamnose released from plant cell walls by the cellulolytic soil bacterium Clostridium phytofermentans produces toxic aldehyde intermediates. To enable growth on these carbon sources, the pathway for the breakdown of fucose and rhamnose is encapsulated within a bacterial microcompartment (BMC). These proteinaceous organelles sequester the toxic aldehyde intermediates and allow the efficient action of acylating aldehyde dehydrogenase enzymes to produce an acyl-CoA that is ultimately used in substrate-level phosphorylation to produce ATP. Here we analyse the kinetics of the aldehyde dehydrogenase enzyme from the fucose/rhamnose utilisation BMC with different short-chain fatty aldehydes and show that it has activity against substrates with up to six carbon atoms, with optimal activity against propionaldehyde. We have also determined the X-ray crystal structure of this enzyme in complex with CoA and show that the adenine nucleotide of this cofactor is bound in a distinct pocket to the same group in NAD(+). This work is the first report of the structure of CoA bound to an aldehyde dehydrogenase enzyme and our crystallographic model provides important insight into the differences within the active site that distinguish the acylating from non-acylating aldehyde dehydrogenase enzymes.

  9. Profiling acylated homoserine lactones in Yersinia ruckeri and influence of exogenous acyl homoserine lactones and known quorum-sensing inhibitors on protease production

    Kastbjerg, Vicky Gaedt; Nielsen, Kristian Fog; Dalsgaard, Inger

    2007-01-01

    produced at least eight different acylated homoserine lactones (AHLs) with N-(3-oxooctanoyl)-l-homoserine lactone (3-oxo-C8-HSL) being the dominant molecule. Also, some uncommon AHL, N-(3-oxoheptanoyl)-l-homoserine lactone (3-oxo-C7-HSL) and N-(3-oxononanoyl)-l-homoserine lactone (3-oxo-C9-HSL), were...

  10. Effect of heterologous expression of acyl-CoA-binding protein on acyl-CoA level and composition in yeast

    Mandrup, S; Jepsen, R; Skøtt, H

    1993-01-01

    We have expressed a bovine synthetic acyl-CoA-binding protein (ACBP) gene in yeast (Saccharomyces cerevisiae) under the control of the GAL1 promoter. The heterologously expressed bovine ACBP constituted up to 6.4% of total cellular protein and the processing was identical with that of native bovi...

  11. OleA Glu117 is key to condensation of two fatty-acyl coenzyme A substrates in long-chain olefin biosynthesis

    Jensen, Matthew R.; Goblirsch, Brandon R.; Christenson, James K.; Esler, Morgan A.; Mohamed, Fatuma A.; Wackett, Lawrence P.; Wilmot, Carrie M. (UMM)

    2017-10-12

    In the interest of decreasing dependence on fossil fuels, microbial hydrocarbon biosynthesis pathways are being studied for renewable, tailored production of specialty chemicals and biofuels. One candidate is long-chain olefin biosynthesis, a widespread bacterial pathway that produces waxy hydrocarbons. Found in three- and four-gene clusters, oleABCD encodes the enzymes necessary to produce cis-olefins that differ by alkyl chain length, degree of unsaturation, and alkyl chain branching. The first enzyme in the pathway, OleA, catalyzes the Claisen condensation of two fatty acyl-coenzyme A (CoA) molecules to form a β-keto acid. In this report, the mechanistic role of Xanthomonas campestris OleA Glu117 is investigated through mutant enzymes. Crystal structures were determined for each mutant as well as their complex with the inhibitor cerulenin. Complemented by substrate modeling, these structures suggest that Glu117 aids in substrate positioning for productive carbon–carbon bond formation. Analysis of acyl-CoA substrate hydrolysis shows diminished activity in all mutants. When the active site lacks an acidic residue in the 117 position, OleA cannot form condensed product, demonstrating that Glu117 has a critical role upstream of the essential condensation reaction. Profiling of pH dependence shows that the apparent pKa for Glu117 is affected by mutagenesis. Taken together, we propose that Glu117 is the general base needed to prime condensation via deprotonation of the second, non-covalently bound substrate during turnover. This is the first example of a member of the thiolase superfamily of condensing enzymes to contain an active site base originating from the second monomer of the dimer.

  12. A Canonical Biotin Synthesis Enzyme, 8-Amino-7-Oxononanoate Synthase (BioF), Utilizes Different Acyl Chain Donors in Bacillus subtilis and Escherichia coli.

    Manandhar, Miglena; Cronan, John E

    2018-01-01

    BioF (8-amino-7-oxononanoate synthase) is a strictly conserved enzyme that catalyzes the first step in assembly of the fused heterocyclic rings of biotin. The BioF acyl chain donor has long been thought to be pimeloyl-CoA. Indeed, in vitro the Escherichia coli and Bacillus sphaericus enzymes have been shown to condense pimeloyl-CoA with l-alanine in a pyridoxal 5'-phosphate-dependent reaction with concomitant CoA release and decarboxylation of l-alanine. However, recent in vivo studies of E. coli and Bacillus subtilis suggested that the BioF proteins of the two bacteria could have different specificities for pimelate thioesters in that E. coli BioF may utilize either pimeloyl coenzyme A (CoA) or the pimelate thioester of the acyl carrier protein (ACP) of fatty acid synthesis. In contrast, B. subtilis BioF seemed likely to be specific for pimeloyl-CoA and unable to utilize pimeloyl-ACP. We now report genetic and in vitro data demonstrating that B. subtilis BioF specifically utilizes pimeloyl-CoA. IMPORTANCE Biotin is an essential vitamin required by mammals and birds because, unlike bacteria, plants, and some fungi, these organisms cannot make biotin. Currently, the biotin included in vitamin tablets and animal feeds is made by chemical synthesis. This is partly because the biosynthetic pathways in bacteria are incompletely understood. This paper defines an enzyme of the Bacillus subtilis pathway and shows that it differs from that of Escherichia coli in the ability to utilize specific precursors. These bacteria have been used in biotin production and these data may aid in making biotin produced by biotechnology commercially competitive with that produced by chemical synthesis. Copyright © 2017 American Society for Microbiology.

  13. Both acyl and des-acyl ghrelin regulate adiposity and glucose metabolism via central nervous system ghrelin receptors.

    Heppner, Kristy M; Piechowski, Carolin L; Müller, Anne; Ottaway, Nickki; Sisley, Stephanie; Smiley, David L; Habegger, Kirk M; Pfluger, Paul T; Dimarchi, Richard; Biebermann, Heike; Tschöp, Matthias H; Sandoval, Darleen A; Perez-Tilve, Diego

    2014-01-01

    Growth hormone secretagogue receptors (GHSRs) in the central nervous system (CNS) mediate hyperphagia and adiposity induced by acyl ghrelin (AG). Evidence suggests that des-AG (dAG) has biological activity through GHSR-independent mechanisms. We combined in vitro and in vivo approaches to test possible GHSR-mediated biological activity of dAG. Both AG (100 nmol/L) and dAG (100 nmol/L) significantly increased inositol triphosphate formation in human embryonic kidney-293 cells transfected with human GHSR. As expected, intracerebroventricular infusion of AG in mice increased fat mass (FM), in comparison with the saline-infused controls. Intracerebroventricular dAG also increased FM at the highest dose tested (5 nmol/day). Chronic intracerebroventricular infusion of AG or dAG increased glucose-stimulated insulin secretion (GSIS). Subcutaneously infused AG regulated FM and GSIS in comparison with saline-infused control mice, whereas dAG failed to regulate these parameters even with doses that were efficacious when delivered intracerebroventricularly. Furthermore, intracerebroventricular dAG failed to regulate FM and induce hyperinsulinemia in GHSR-deficient (Ghsr(-/-)) mice. In addition, a hyperinsulinemic-euglycemic clamp suggests that intracerebroventricular dAG impairs glucose clearance without affecting endogenous glucose production. Together, these data demonstrate that dAG is an agonist of GHSR and regulates body adiposity and peripheral glucose metabolism through a CNS GHSR-dependent mechanism.

  14. Acyl Chain Preference in Foam Cell Formation from Mouse Peritoneal Macrophages.

    Fujiwara, Yuko; Hama, Kotaro; Tsukahara, Makoto; Izumi-Tsuzuki, Ryosuke; Nagai, Toru; Ohe-Yamada, Mihoko; Inoue, Keizo; Yokoyama, Kazuaki

    2018-01-01

    Macrophage foam cells play critical roles in the initiation and development of atherosclerosis by synthesizing and accumulating cholesteryl ester (CE) in lipid droplets. However, in analyzing lipid metabolism in foam cell formation, studies have focused on the sterol group, and little research has been done on the acyl chains. Therefore, we adapted a model system using liposomes containing particular acyl chains and examined the effect of various acyl chains on foam cell formation. Of the phosphatidylserine (PS) liposomes tested containing PS, phosphatidylcholine, and cholesterol, we found that unsaturated (C18:1), but not saturated (C16:0 and C18:0), PS liposomes induced lipid droplet formation, indicating that foam cell formation depends on the nature of the acyl chain of the PS liposomes. Experiments on the uptake and accumulation of cholesterol from liposomes by adding [ 14 C]cholesterol suggested that foam cell formation could be induced only when cholesterol was converted to CE in the case of C18:1 PS liposomes. Both microscopic observations and metabolic analysis suggest that cholesterol incorporated into either C16:0 or C18:0 PS liposomes may stay intact after being taken in by endosomes. The [ 14 C]C18:1 fatty acyl chain in the C18:1 PS liposome was used to synthesize CE and triacylglycerol (TG). Interestingly, the [ 14 C]C16:0 in the C18:1 PS liposome was metabolized to sphingomyelin rather than being incorporated into either CE or TG, which could be because of enzymatic acyl chain selectivity. In conclusion, our results indicate that the acyl chain preference of macrophages could have some impact on their progression to foam cells.

  15. Acute effect of exercise intensity and duration on acylated ghrelin and hunger in men.

    Broom, David R; Miyashita, Masashi; Wasse, Lucy K; Pulsford, Richard; King, James A; Thackray, Alice E; Stensel, David J

    2017-03-01

    Acute exercise transiently suppresses the orexigenic gut hormone acylated ghrelin, but the extent to which exercise intensity and duration determine this response is not fully understood. The effects of manipulating exercise intensity and duration on acylated ghrelin concentrations and hunger were examined in two experiments. In experiment one, nine healthy males completed three, 4-h conditions (control, moderate-intensity running (MOD) and vigorous-intensity running (VIG)), with an energy expenditure of ~2.5 MJ induced in both MOD (55-min running at 52% peak oxygen uptake (V.O 2peak )) and VIG (36-min running at 75% V.O 2peak ). In experiment two, nine healthy males completed three, 9-h conditions (control, 45-min running (EX45) and 90-min running (EX90)). Exercise was performed at 70% V.O 2peak In both experiments, participants consumed standardised meals, and acylated ghrelin concentrations and hunger were quantified at predetermined intervals. In experiment one, delta acylated ghrelin concentrations were lower than control in MOD (ES = 0.44, P = 0.01) and VIG (ES = 0.98, P Hunger ratings were similar across the conditions (P = 0.35). In experiment two, delta acylated ghrelin concentrations were lower than control in EX45 (ES = 0.77, P Hunger ratings were lower than control in EX45 (ES = 0.20, P = 0.01) and EX90 (ES = 0.27, P = 0.001); EX45 and EX90 were similar (ES = 0.07, P = 0.34). Hunger and delta acylated ghrelin concentrations remained suppressed at 1.5 h in EX90 but not EX45. In conclusion, exercise intensity, and to a lesser extent duration, are determinants of the acylated ghrelin response to acute exercise. © 2017 Society for Endocrinology.

  16. Disruption of the acyl-coa binding protein gene delays hepatic adaptation to metabolic changes at weaning

    Neess, Ditte; Bloksgaard, Maria; Sørensen, Signe Bek

    2011-01-01

    The acyl-CoA binding protein/diazepam binding inhibitor (ACBP/DBI) is an intracellular protein that binds C14-C22 acyl-CoA esters and is thought to act as an acyl-CoA transporter. In vitro analyses have indicated that ACBP can transport acyl-CoA esters between different enzymatic systems; however....... The delayed induction of SREBP target genes around weaning is caused by a compromised processing and decreased expression of SREBP precursors leading to reduced binding of SREBP to target sites in chromatin. In conclusion, lack of ACBP interferes with the normal metabolic adaptation to weaning and leads...

  17. Characterization of a stearoyl-acyl carrier protein desaturase gene family from chocolate tree, Theobroma cacao L

    Zhang, Yufan; Maximova, Siela N.; Guiltinan, Mark J.

    2015-01-01

    In plants, the conversion of stearoyl-ACP to oleoyol-ACP is catalyzed by a plastid-localized soluble stearoyl-acyl carrier protein (ACP) desaturase (SAD). The activity of SAD significantly impacts the ratio of saturated and unsaturated fatty acids, and is thus a major determinant of fatty acid composition. The cacao genome contains eight putative SAD isoforms with high amino acid sequence similarities and functional domain conservation with SAD genes from other species. Sequence variation in known functional domains between different SAD family members suggested that these eight SAD isoforms might have distinct functions in plant development, a hypothesis supported by their diverse expression patterns in various cacao tissues. Notably, TcSAD1 is universally expressed across all the tissues, and its expression pattern in seeds is highly correlated with the dramatic change in fatty acid composition during seed maturation. Interestingly, TcSAD3 and TcSAD4 appear to be exclusively and highly expressed in flowers, functions of which remain unknown. To test the function of TcSAD1 in vivo, transgenic complementation of the Arabidopsis ssi2 mutant was performed, demonstrating that TcSAD1 successfully rescued all AtSSI2 related phenotypes further supporting the functional orthology between these two genes. The identification of the major SAD gene responsible for cocoa butter biosynthesis provides new strategies for screening for novel genotypes with desirable fatty acid compositions, and for use in breeding programs to help pyramid genes for quality and other traits such as disease resistance. PMID:25926841

  18. Characterization of a stearoyl-acyl carrier protein desaturase gene family from chocolate tree, Theobroma cacao L.

    Zhang, Yufan; Maximova, Siela N; Guiltinan, Mark J

    2015-01-01

    In plants, the conversion of stearoyl-ACP to oleoyol-ACP is catalyzed by a plastid-localized soluble stearoyl-acyl carrier protein (ACP) desaturase (SAD). The activity of SAD significantly impacts the ratio of saturated and unsaturated fatty acids, and is thus a major determinant of fatty acid composition. The cacao genome contains eight putative SAD isoforms with high amino acid sequence similarities and functional domain conservation with SAD genes from other species. Sequence variation in known functional domains between different SAD family members suggested that these eight SAD isoforms might have distinct functions in plant development, a hypothesis supported by their diverse expression patterns in various cacao tissues. Notably, TcSAD1 is universally expressed across all the tissues, and its expression pattern in seeds is highly correlated with the dramatic change in fatty acid composition during seed maturation. Interestingly, TcSAD3 and TcSAD4 appear to be exclusively and highly expressed in flowers, functions of which remain unknown. To test the function of TcSAD1 in vivo, transgenic complementation of the Arabidopsis ssi2 mutant was performed, demonstrating that TcSAD1 successfully rescued all AtSSI2 related phenotypes further supporting the functional orthology between these two genes. The identification of the major SAD gene responsible for cocoa butter biosynthesis provides new strategies for screening for novel genotypes with desirable fatty acid compositions, and for use in breeding programs to help pyramid genes for quality and other traits such as disease resistance.

  19. Structural rearrangements occurring upon cofactor binding in the Mycobacterium smegmatis β-ketoacyl-acyl carrier protein reductase MabA.

    Küssau, Tanja; Flipo, Marion; Van Wyk, Niel; Viljoen, Albertus; Olieric, Vincent; Kremer, Laurent; Blaise, Mickaël

    2018-05-01

    In mycobacteria, the ketoacyl-acyl carrier protein (ACP) reductase MabA (designated FabG in other bacteria) catalyzes the NADPH-dependent reduction of β-ketoacyl-ACP substrates to β-hydroxyacyl-ACP products. This first reductive step in the fatty-acid biosynthesis elongation cycle is essential for bacteria, which makes MabA/FabG an interesting drug target. To date, however, very few molecules targeting FabG have been discovered and MabA remains the only enzyme of the mycobacterial type II fatty-acid synthase that lacks specific inhibitors. Despite the existence of several MabA/FabG crystal structures, the structural rearrangement that occurs upon cofactor binding is still not fully understood. Therefore, unlocking this knowledge gap could help in the design of new inhibitors. Here, high-resolution crystal structures of MabA from Mycobacterium smegmatis in its apo, NADP + -bound and NADPH-bound forms are reported. Comparison of these crystal structures reveals the structural reorganization of the lid region covering the active site of the enzyme. The crystal structure of the apo form revealed numerous residues that trigger steric hindrance to the binding of NADPH and substrate. Upon NADPH binding, these residues are pushed away from the active site, allowing the enzyme to adopt an open conformation. The transition from an NADPH-bound to an NADP + -bound form is likely to facilitate release of the product. These results may be useful for subsequent rational drug design and/or for in silico drug-screening approaches targeting MabA/FabG.

  20. In-source formation of N-acetyl-p-benzoquinone imine (NAPQI), the putatively toxic acetaminophen (paracetamol) metabolite, after derivatization with pentafluorobenzyl bromide and GC-ECNICI-MS analysis.

    Tsikas, Dimitrios; Trettin, Arne; Zörner, Alexander A; Gutzki, Frank-Mathias

    2011-05-15

    Pentafluorobenzyl (PFB) bromide (PFB-Br) is a versatile derivatization reagent for numerous classes of compounds. Under electron-capture negative-ion chemical ionization (ECNICI) conditions PFB derivatives of acidic compounds readily and abundantly ionize to produce intense anions due to [M-PFB](-). In the present article we investigated the PFB-Br derivatization of unlabelled acetaminophen (N-acetyl-p-aminophenol, NAPAP-d(0); paracetamol; MW 151) and tetradeuterated acetaminophen (NAPAP-d(4); MW 155) in anhydrous acetonitrile and their GC-ECNICI-MS behavior using methane as the buffer gas. In addition to the expected anions [M-PFB](-) at m/z 150 from NAPAP-d(0) and m/z 154 from NAPAP-d(4), we observed highly reproducibly almost equally intense anions at m/z 149 and m/z 153, respectively. Selected ion monitoring of these ions is suitable for specific and sensitive quantification of acetaminophen in human plasma and urine. Detailed investigations suggest in-source formation of N-acetyl-p-benzoquinone imine (NAPQI; MW 149), the putatively toxic acetaminophen metabolite, from the PFB ether derivative of NAPAP. GC-ECNICI-MS of non-derivatized NAPAP did not produce NAPQI. The peak area ratio of m/z 149 to m/z 150 and of m/z 153 to m/z 154 decreased with increasing ion-source temperature in the range 100-250°C. Most likely, NAPQI formed in the ion-source captures secondary electrons to become negatively charged (i.e., [NAPQI](-)) and thus detectable. Formation of NAPQI was not observed under electron ionization (EI) conditions, i.e., by GC-EI-MS, from derivatized and non-derivatized NAPAP. NAPQI was not detectable in flow injection analysis LC-MS of native NAPAP in positive electrospray ionization (ESI) mode, whereas in negative ESI mode low extent NAPQI formation was observed (<5%). Our results suggest that oxidation of drug derivatives in the ion-sources of mass spectrometers may form intermediates that are produced from activated drugs in enzyme-catalyzed reactions

  1. Potential of acylated peptides to target the influenza A virus

    Daniel Lauster

    2015-04-01

    Full Text Available For antiviral drug design, especially in the field of influenza virus research, potent multivalent inhibitors raise high expectations for combating epidemics and pandemics. Among a large variety of covalent and non-covalent scaffold systems for a multivalent display of inhibitors, we created a simple supramolecular platform to enhance the antiviral effect of our recently developed antiviral Peptide B (PeBGF, preventing binding of influenza virus to the host cell. By conjugating the peptide with stearic acid to create a higher-order structure with a multivalent display, we could significantly enhance the inhibitory effect against the serotypes of both human pathogenic influenza virus A/Aichi/2/1968 H3N2, and avian pathogenic A/FPV/Rostock/34 H7N1 in the hemagglutination inhibition assay. Further, the inhibitory potential of stearylated PeBGF (C18-PeBGF was investigated by infection inhibition assays, in which we achieved low micromolar inhibition constants against both viral strains. In addition, we compared C18-PeBGF to other published amphiphilic peptide inhibitors, such as the stearylated sugar receptor mimicking peptide (Matsubara et al. 2010, and the “Entry Blocker” (EB (Jones et al. 2006, with respect to their antiviral activity against infection by Influenza A Virus (IAV H3N2. However, while this strategy seems at a first glance promising, the native situation is quite different from our experimental model settings. First, we found a strong potential of those peptides to form large amyloid-like supramolecular assemblies. Second, in vivo, the large excess of cell surface membranes provides an unspecific target for the stearylated peptides. We show that acylated peptides insert into the lipid phase of such membranes. Eventually, our study reveals serious limitations of this type of self-assembling IAV inhibitors.

  2. Acylation of cellular proteins with endogenously synthesized fatty acids

    Towler, D.; Glaser, L.

    1986-01-01

    A number of cellular proteins contain covalently bound fatty acids. Previous studies have identified myristic acid and palmitic acid covalently linked to protein, the former usually attached to proteins by an amide linkage and the latter by ester or thio ester linkages. While in a few instances specific proteins have been isolated from cells and their fatty acid composition has been determined, the most frequent approach to the identification of protein-linked fatty acids is to biosynthetically label proteins with fatty acids added to intact cells. This procedure introduces possible bias in that only a selected fraction of proteins may be labeled, and it is not known whether the radioactive fatty acid linked to the protein is identical with that which is attached to the protein when the fatty acid is derived from endogenous sources. We have examined the distribution of protein-bound fatty acid following labeling with [ 3 H]acetate, a general precursor of all fatty acids, using BC 3 H1 cells (a mouse muscle cell line) and A431 cells (a human epidermoid carcinoma). Myristate, palmitate, and stearate account for essentially all of the fatty acids linked to protein following labeling with [ 3 H]acetate, but at least 30% of the protein-bound palmitate in these cells was present in amide linkage. In BC3H1 cells, exogenous palmitate becomes covalently bound to protein such that less than 10% of the fatty acid is present in amide linkage. These data are compatible with multiple protein acylating activities specific for acceptor protein fatty acid chain length and linkage

  3. Arabidopsis PIZZA has the capacity to acylate brassinosteroids.

    Schneider, Katja; Breuer, Christian; Kawamura, Ayako; Jikumaru, Yusuke; Hanada, Atsushi; Fujioka, Shozo; Ichikawa, Takanari; Kondou, Youichi; Matsui, Minami; Kamiya, Yuji; Yamaguchi, Shinjiro; Sugimoto, Keiko

    2012-01-01

    Brassinosteroids (BRs) affect a wide range of developmental processes in plants and compromised production or signalling of BRs causes severe growth defects. To identify new regulators of plant organ growth, we searched the Arabidopsis FOX (Full-length cDNA Over-eXpressor gene) collection for mutants with altered organ size and isolated two overexpression lines that display typical BR deficient dwarf phenotypes. The phenotype of these lines, caused by an overexpression of a putative acyltransferase gene PIZZA (PIZ), was partly rescued by supplying exogenous brassinolide (BL) and castasterone (CS), indicating that endogenous BR levels are rate-limiting for the growth of PIZ overexpression lines. Our transcript analysis further showed that PIZ overexpression leads to an elevated expression of genes involved in BR biosynthesis and a reduced expression of BR inactivating hydroxylases, a transcriptional response typical to low BR levels. Taking the advantage of relatively high endogenous BR accumulation in a mild bri1-301 background, we found that overexpression of PIZ results in moderately reduced levels of BL and CS and a strong reduction of typhasterol (TY) and 6-deoxocastasterone (6-deoxoCS), suggesting a role of PIZ in BR metabolism. We tested a set of potential substrates in vitro for heterologously expressed PIZ and confirmed its acyltransferase activity with BL, CS and TY. The PIZ gene is expressed in various tissues but as reported for other genes involved in BR metabolism, the loss-of-function mutants did not display obvious growth phenotypes under standard growth conditions. Together, our data suggest that PIZ can modify BRs by acylation and that these properties might help modulating endogenous BR levels in Arabidopsis.

  4. Cold fusion catalyzed by muons and electrons

    Kulsrud, R.M.

    1990-10-01

    Two alternative methods have been suggested to produce fusion power at low temperature. The first, muon catalyzed fusion or MCF, uses muons to spontaneously catalyze fusion through the muon mesomolecule formation. Unfortunately, this method fails to generate enough fusion energy to supply the muons, by a factor of about ten. The physics of MCF is discussed, and a possible approach to increasing the number of MCF fusions generated by each muon is mentioned. The second method, which has become known as ''Cold Fusion,'' involves catalysis by electrons in electrolytic cells. The physics of this process, if it exists, is more mysterious than MCF. However, it now appears to be an artifact, the claims for its reality resting largely on experimental errors occurring in rather delicate experiments. However, a very low level of such fusion claimed by Jones may be real. Experiments in cold fusion will also be discussed

  5. Characterization of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme of human small intestine.

    Hiramine, Yasushi; Tanabe, Toshizumi

    2011-06-01

    Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme plays a significant role in dietary triacylglycerol (TAG) absorption in the small intestine. However, the characteristics of human intestinal DGAT enzyme have not been examined in detail. The aim of our study was to characterize the human intestinal DGAT enzyme by examining acyl-CoA specificity, temperature dependency, and selectivity for 1,2-diacylglycerol (DAG) or 1,3-DAG. We detected DGAT activity of human intestinal microsome and found that the acyl-CoA specificity and temperature dependency of intestinal DGAT coincided with those of recombinant human DGAT1. To elucidate the selectivity of human intestinal DGAT to 1,2-DAG or 1,3-DAG, we conducted acyl-coenzyme A:monoacylglycerol acyltransferase assays using 1- or 2-monoacylglycerol (MAG) as substrates. When 2-MAG was used as acyl acceptor, both 1,2-DAG and TAG were generated; however, when 1-MAG was used, 1,3-DAG was predominantly observed and little TAG was detected. These findings suggest that human small intestinal DGAT, which is mainly encoded by DGAT1, utilizes 1,2-DAG as the substrate to form TAG. This study will contribute to understand the lipid absorption profile in the small intestine.

  6. Engineered Production of Short-Chain Acyl-Coenzyme A Esters in Saccharomyces cerevisiae

    Krink-Koutsoubelis, Nicolas; Loechner, Anne C.; Lechner, Anna

    2018-01-01

    Short-chain acyl-coenzyme A esters serve as intermediate compounds in fatty acid biosynthesis, and the production of polyketides, biopolymers and other value-added chemicals. S. cerevisiae is a model organism that has been utilized for the biosynthesis of such biologically and economically valuable...... compounds. However, its limited repertoire of short-chain acyl-CoAs effectively prevents its application as a production host for a plethora of natural products. Therefore, we introduced biosynthetic metabolic pathways to five different acyl-CoA esters into S. cerevisiae. Our engineered strains provide......-CoA at 0.5 μM; and isovaleryl-CoA, n-butyryl-CoA, and n-hexanoyl-CoA at 6 μM each. The acyl-CoAs produced in this study are common building blocks of secondary metabolites and will enable the engineered production of a variety of natural products in S. cerevisiae. By providing this toolbox of acyl...

  7. THE EFFECTS OF EXERCISE ON FOOD INTAKE AND HUNGER: RELATIONSHIP WITH ACYLATED GHRELIN AND LEPTIN

    Serife Vatansever-Ozen

    2011-06-01

    Full Text Available This study investigated the effects of a long bout of aerobic exercise on hunger and energy intake and circulating levels of leptin and acylated ghrelin. Ten healthy male subjects undertook two, 4 h trials in a randomized crossover design. In the exercise trial subjects ran for 105 min at 50% of maximal oxygen uptake and the last 15 min at 70% of maximal oxygen uptake followed by a 120 min rest period. In the control trial, subjects rested for 4 h. Subjects consumed a buffet test meal at 180 min during each trial. Hunger ratings, acylated ghrelin, leptin, glucose and insulin concentrations were measured at 0, 1, 2, 3 and 4 h. No differences were found at baseline values for hunger, acylated ghrelin, leptin, insulin and glucose for both trials (p > 0.05. The estimated energy expenditure of the exercise trial was 1550 ± 136 kcal. Exercise did not change subsequent absolute energy intake, but produced a significant decrease (p < 0.05 in relative energy intake. A two-way ANOVA revealed a significant (p < 0. 05 interaction effect for hunger and acylated ghrelin. In conclusion, this exercise regimen had a positive effect on reducing appetite which is related to reduced acylated ghrelin responses over time. This finding lends support for a role of exercise in weight management

  8. Targeted Lipidomics in Drosophila melanogaster Identifies Novel 2-Monoacylglycerols and N-acyl Amides

    Takacs, Sara M.; Stuart, Jordyn M.; Basnet, Arjun; Raboune, Siham; Widlanski, Theodore S.; Doherty, Patrick; Bradshaw, Heather B.

    2013-01-01

    Lipid metabolism is critical to coordinate organ development and physiology in response to tissue-autonomous signals and environmental cues. Changes to the availability and signaling of lipid mediators can limit competitiveness, adaptation to environmental stressors, and augment pathological processes. Two classes of lipids, the N-acyl amides and the 2-acyl glycerols, have emerged as important signaling molecules in a wide range of species with important signaling properties, though most of what is known about their cellular functions is from mammalian models. Therefore, expanding available knowledge on the repertoire of these lipids in invertebrates will provide additional avenues of research aimed at elucidating biosynthetic, metabolic, and signaling properties of these molecules. Drosophila melanogaster is a commonly used organism to study intercellular communication, including the functions of bioactive lipids. However, limited information is available on the molecular identity of lipids with putative biological activities in Drosophila. Here, we used a targeted lipidomics approach to identify putative signaling lipids in third instar Drosophila larvae, possessing particularly large lipid mass in their fat body. We identified 2-linoleoyl glycerol, 2-oleoyl glycerol, and 45 N-acyl amides in larval tissues, and validated our findings by the comparative analysis of Oregon-RS, Canton-S and w1118 strains. Data here suggest that Drosophila represent another model system to use for the study of 2-acyl glycerol and N-acyl amide signaling. PMID:23874457

  9. Gold nanoparticles capped with benzalkonium chloride and poly (ethylene imine) for enhanced loading and skin permeability of 5-fluorouracil.

    Safwat, Mohamed A; Soliman, Ghareb M; Sayed, Douaa; Attia, Mohamed A

    2017-11-01

    To enhance 5-fluorouracil (5-FU) permeability through the skin by loading onto gold nanoparticles (GNPs) capped with two cationic ligands, benzalkonium chloride (BC) or poly (ethylene imine) (PEI). Whereas 5-FU has excellent efficacy against many cancers, its poor permeability through biological membranes and several adverse effects limit its clinical benefits. BC and PEI were selected to stabilize GNPs and to load 5-FU through ionic interactions. 5-FU/BC-GNPs and 5-FU/PEI-GNPs were prepared at different 5-FU/ligand molar ratios and different pH values and were evaluated using different techniques. GNPs stability was tested as a function of salt concentration and storage time. 5-FU release from BC- and PEI-GNPs was evaluated as a function of solution pH. Ex vivo permeability studies of different 5-FU preparations were carried out using mice skin. 5-FU-loaded GNPs size and surface charge were dependent on the 5-FU/ligand molar ratios. 5-FU entrapment efficiency and loading capacity were dependent on the used ligand, 5-FU/ligand molar ratio and solution pH. Maximum drug entrapment efficiency of 59.0 ± 1.7% and 46.0 ± 1.1% were obtained for 5-FU/BC-GNPs and 5-FU/PEI-GNPs, respectively. 5-FU-loaded GNPs had good stability against salinity and after storage for 4 months at room temperature and at 4 °C. In vitro 5-FU release was pH- and ligand-dependent where slower release was observed at higher pH and for 5-FU/BC-GNPs. 5-FU permeability through mice skin was significantly higher for drug-loaded GNPs compared with drug-ligand complex or drug aqueous solution. Based on these results, BC- and PEI-GNPs might find applications as effective topical delivery systems of 5-FU.

  10. Ionic Conductivity and Potential Application for Fuel Cell of a Modified Imine-Based Covalent Organic Framework.

    Montoro, Carmen; Rodríguez-San-Miguel, David; Polo, Eduardo; Escudero-Cid, Ricardo; Ruiz-González, Maria Luisa; Navarro, Jorge A R; Ocón, Pilar; Zamora, Félix

    2017-07-26

    We present the novel potential application of imine-based covalent organic frameworks (COFs), formed by the direct Schiff reaction between 1,3,5-tris(4-aminophenyl)benzene and 1,3,5-benzenetricarbaldehyde building blocks in m-cresol or acetic acid, named RT-COF-1 or RT-COF-1Ac/RT-COF-1AcB. The post-synthetic treatment of RT-COF-1 with LiCl leads to the formation of LiCl@RT-COF-1. The ionic conductivity of this series of polyimine COFs has been characterized at variable temperature and humidity, using electrochemical impedance spectroscopy. LiCl@RT-COF-1 exhibits a conductivity value of 6.45 × 10 -3 S cm -1 (at 313 K and 100% relative humidity) which is among the highest values so far reported in proton conduction for COFs. The mechanism of conduction has been determined using 1 H and 7 Li solid-state nuclear magnetic resonance spectroscopy. Interestingly, these materials, in the presence of controlled amounts of acetic acid and under pressure, show a remarkable processability that gives rise to quasi-transparent and flexible films showing in-plane structural order as confirmed by X-ray crystallography. Finally, we prove that these films are useful for the construction of proton exchange membrane fuel cells (PEMFC) reaching values up to 12.95 mW cm -2 and 53.1 mA cm -2 for maximum power and current density at 323 K, respectively.

  11. Synthesis and characterization of poly(propylene imine)-dendrimer-grafted gold nanoparticles as nanocarriers of doxorubicin.

    Golshan, Marzieh; Salami-Kalajahi, Mehdi; Mirshekarpour, Mina; Roghani-Mamaqani, Hossein; Mohammadi, Maryam

    2017-07-01

    The aim of current work is synthesis 4th-generation-poly(propylene imine) (PPI)-dendrimer modified gold nanoparticles (Au-G4A) as nanocarriers for doxorubicin (DOX) and studying in vitro drug release kinetics from nanocarriers into different media. Accordingly, AuNPs were synthesized by reduction of chloroauric acid (HAuCl 4 ) aqueous solution with trisodium citrate and modified with cysteamine to obtain amine-functionalized (Au-NH 2 ) nanoparticles. Au-NH 2 nanoparticles were used as multifunctional cores and participated in Michael addition of acrylonitrile and reduction process by lithium aluminum hydride (LAH) to synthesize Au-G4A nanoparticles. Also, peripheral primary amine groups of Au-G4A were conjugated with folic acid (FA) (Au-G4F) to study the bioconjugation effect on drug release behavior of nanostructures. Ultraviolet spectroscopy (UV-vis), atomic force microscopy (AFM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) were used to approve the synthesis of different nanostructures. Finally, Au-G4A and Au-G4F samples were loaded with DOX and exposed to environments with different pH values to examine the release properties of nanostructures. Also, drug release kinetics was investigated by fitting of experimental data with different release models. As a result, synthesized dendritic structures showed Higuchi and Korsmeyer-Peppas models release behavior due to better solubility of drug in release media with respect to dendrimer cavities and drug release through polymeric matrix respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. A Highly Stable Microporous Covalent Imine Network Adsorbent for Natural Gas Upgrading and Flue Gas CO2 Capture

    Das, Swapan Kumar

    2016-06-06

    The feasible capture and separation of CO2 and N2 from CH4 is an important task for natural gas upgrading and the control of greenhouse gas emissions. Here, we studied the microporous covalent imine networks (CIN) material prepared through Schiff base condensation and exhibited superior chemical robustness under both acidic and basic conditions and high thermal stability. The material possesses a relatively uniform nanoparticle size of approximately 70 to 100 nm. This network featured permanent porosity with a high surface area (722 m2g-1) and micropores. A single-component gas adsorption study showed enhanced CO2 and CH4 uptakes of 3.32 mmol/g and 1.14 mmol/g, respectively, at 273 K and 1 bar, coupled with high separation selectivities for CO2/CH4, CH4/N2, and CO2/N2 of 23, 11.8 and 211, respectively. The enriched Lewis basicity in the porous skeletons favours the interaction of quadrupolar CO2 and polarizable CH4, resulting in enhanced CH4 and CO2 uptake and high CH4/N2, CO2/CH4 and CO2/N2 selectivities. Breakthrough experiments showed high CO2/CH4, CH4/N2 and CO2/N2 selectivities of 7.29, 40 and 125, respectively, at 298 K and 1 bar. High heats of adsorption for CH4 and CO2 (QstCH4; 32.61 kJ mol-1 and QstCO2; 42.42 kJ mol-1) provide the ultimate validation for the high selectivity. To the best of our knowledge, such a versatile adsorbent material that displays both enhanced uptake and selectivity for a variety of binary gas mixtures, including CO2/ CH4, CO2/N2 and CH4/N2, has not been extensively explored.

  13. Efficient water removal in lipase-catalyzed esterifications using a low-boiling-point azeotrope.

    Yan, Youchun; Bornscheuer, Uwe T; Schmid, Rolf D

    2002-04-05

    High conversions in lipase-catalyzed syntheses of esters from free acyl donors and an alcohol requires efficient removal of water preferentially at temperatures compatible to enzyme activity. Using a lipase B from Candida antarctica (CAL-B)-mediated synthesis of sugar fatty-acid esters, we show that a mixture of ethyl methylketone (EMK) and hexane (best ratio: 4:1, vo/vo) allows efficient removal of water generated during esterification. Azeotropic distillation of the solvent mixture (composition: 26% EMK, 55% hexane, 19% water) takes place at 59 degrees C, which closely matches the optimum temperature reported for CAL-B. Water is then removed from the azeotrope by membrane vapor permeation. In case of glucose stearate, 93% yield was achieved after 48 h using an equimolar ratio of glucose and stearic acid. CAL-B could be reused for seven reaction cycles, with 86% residual activity after 14 d total reaction time at 59 degrees C. A decrease in fatty-acid chain length as well as increasing temperatures (75 degrees C) resulted in lower conversions. In addition, immobilization of CAL-B on a magnetic polypropylene carrier (EP 100) facilitated separation of the biocatalyst. Copyright 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 31--34, 2002; DOI 10.1002/bit.10084

  14. Desaturation reactions catalyzed by soluble methane monooxygenase.

    Jin, Y; Lipscomb, J D

    2001-09-01

    Soluble methane monooxygenase (MMO) is shown to be capable of catalyzing desaturation reactions in addition to the usual hydroxylation and epoxidation reactions. Dehydrogenated products are generated from MMO-catalyzed oxidation of certain substrates including ethylbenzene and cyclohexadienes. In the reaction of ethylbenzene, desaturation of ethyl C-H occurred along with the conventional hydroxvlations of ethyl and phenyl C-Hs. As a result, styrene is formed together with ethylphenols and phenylethanols. Similarly, when 1,3- and 1,4-cyclohexadienes were used as substrates, benzene was detected as a product in addition to the corresponding alcohols and epoxides. In all cases, reaction conditions were found to significantly affect the distribution among the different products. This new activity of MMO is postulated to be associated with the chemical properties of the substrates rather than fundamental changes in the nature of the oxygen and C-H activation chemistries. The formation of the desaturated products is rationalized by formation of a substrate cationic intermediate, possibly via a radical precursor. The cationic species is then proposed to partition between recombination (alcohol formation) and elimination (alkene production) pathways. This novel function of MMO indicates close mechanistic kinship between the hydroxylation and desaturation reactions catalyzed by the nonheme diiron clusters.

  15. Proghrelin peptides: Desacyl ghrelin is a powerful inhibitor of acylated ghrelin, likely to impair physiological effects of acyl ghrelin but not of obestatin A study of pancreatic polypeptide secretion from mouse islets

    Kumar, Rajesh; Salehi, Albert; Rehfeld, Jens F

    2010-01-01

    Proghrelin, produced by the ghrelin (A-like) cells of the gastric mucosa, gives rise to cleavage products, including desacyl ghrelin, acyl ghrelin and obestatin. The products are thought to be secreted concomitantly. In an earlier study we found acyl ghrelin and obestatin, but not desacyl ghrelin......, to suppress the release of hormones from isolated islets of mouse and rat pancreas....

  16. Proghrelin peptides: Desacyl ghrelin is a powerful inhibitor of acylated ghrelin, likely to impair physiological effects of acyl ghrelin but not of obestatin A study of pancreatic polypeptide secretion from mouse islets

    Kumar, Rajesh; Salehi, Albert; Rehfeld, Jens F

    2010-01-01

    Proghrelin, produced by the ghrelin (A-like) cells of the gastric mucosa, gives rise to cleavage products, including desacyl ghrelin, acyl ghrelin and obestatin. The products are thought to be secreted concomitantly. In an earlier study we found acyl ghrelin and obestatin, but not desacyl ghrelin...

  17. Synthesis of 3-acetyl-N-aryl-4-diethylaminoselenet-2(2H)-imines from 4-diethylamino-3-butyn-2-one and aryl isoselenocyanates

    Atanassov, Plamen K; Linden, Anthony; Heimgartner, Heinz

    2004-01-01

    The reaction of aryl isoselenocyanates (1a-d) with 4-diethylamino-3-butyn-2-one (6) in refluxing tetrahydrofuran afforded N-arylselenet-2(2H)-imines (7) in moderate yields. The structure of the stable 4-bromophenyl derivative (7b) has been established by X-Ray crystallography. A stepwise cycloaddition via an intermediate zwitterion (A/A¢) is proposed as the reaction mechanism. In boiling tetrahydrofuran, the selenetimines (7) are in equilibrium with ketenimines (B), which were intercepted by ...

  18. Quantum-chemical evaluation of the lability of π-electronic systems in N-benzoyl derivatives of phosphorus and sulfur imines

    Egorov, Yu.P.; Pen'kovskii, V.V.; Boldeskul, I.E.

    1986-01-01

    The charges on atoms, the bond indices, their components, and the energies of the highest occupied π orbitals of four N-benzoyl derivatives of phosphorus and sulfur imines have been calculated by the CNDO/2 method in an spd basis. According to the results obtained, the π system of a bridging sulfur-nitrogen group is more labile than a phosphorus-nitrogen group, in agreement with the experimental evaluations of the transmission of the electronic effects of substituents in these systems. An interpretation of this lability has been given

  19. EMR searching of quantum behavior of magnetic γ-Fe2O3 nanoparticles encapsulated into poly(propylene imine dendrimer

    Vorobeva V.E., Domracheva N.E., Gruzdev M.S.

    2016-12-01

    Full Text Available The superparamagnetic γ-Fe2O3 nanoparticles (average diameter of 2.5 nm encapsulated in poly(propylene imine dendrimer have been investigated by electron magnetic resonance (EMR. EMR measurements have been recorded in perpendicular and parallel configurations in the wide temperature range (4.2-300 K. It has been shown that the model based on the spin value S = 30, corresponding to the total magnetic moment of the nanoparticle, can be used to interpret the experimental results and the proof of the quantum behavior of γ-Fe2O3 nanoparticles.

  20. Long Chain N-acyl Homoserine Lactone Production by Enterobacter sp. Isolated from Human Tongue Surfaces

    Yin, Wai-Fong; Purmal, Kathiravan; Chin, Shenyang; Chan, Xin-Yue; Chan, Kok-Gan

    2012-01-01

    We report the isolation of N-acyl homoserine lactone-producing Enterobacter sp. isolate T1-1 from the posterior dorsal surfaces of the tongue of a healthy individual. Spent supernatants extract from Enterobacter sp. isolate T1-1 activated the biosensor Agrobacterium tumefaciens NTL4(pZLR4), suggesting production of long chain AHLs by these isolates. High resolution mass spectrometry analysis of these extracts confirmed that Enterobacter sp. isolate T1-1 produced a long chain N-acyl homoserine lactone, namely N-dodecanoyl-homoserine lactone (C12-HSL). To the best of our knowledge, this is the first isolation of Enterobacter sp., strain T1-1 from the posterior dorsal surface of the human tongue and N-acyl homoserine lactones production by this bacterium. PMID:23202161

  1. Kinetic study on the inhibition of xanthine oxidase by acylated derivatives of flavonoids synthesised enzymatically.

    de Araújo, Maria Elisa Melo Branco; Franco, Yollanda Edwirges Moreira; Alberto, Thiago Grando; Messias, Marcia Cristina Fernandes; Leme, Camila Wielewski; Sawaya, Alexandra Christine Helena Frankland; Carvalho, Patricia de Oliveira

    2017-12-01

    Studies have reported that flavonoids inhibit xanthine oxidase (XO) activity; however, poor solubility and stability in lipophilic media limit their bioavailability and applications. This study evaluated the kinetic parameters of XO inhibition and partition coefficients of flavonoid esters biosynthesised from hesperidin, naringin, and rutin via enzymatic acylation with hexanoic, octanoic, decanoic, lauric, and oleic acids catalysed by Candida antarctica lipase B (CALB). Quantitative determination by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) showed higher conversion yields (%) for naringin and rutin esters using acyl donors with 8C and 10C. Rutin decanoate had higher partition coefficients (0.95), and naringin octanoate and naringin decanoate showed greater inhibitory effects on XO (IC 50 of 110.35 and 117.51 μM, respectively). Kinetic analysis showed significant differences (p flavonoids before and after acylation regarding K m values, whereas the values for V max were the same, implying the competitive nature of XO inhibition.

  2. Commelinid Monocotyledon Lignins Are Acylated by p-Coumarate1[OPEN

    Free, Heather C.A.; Smith, Bronwen G.

    2018-01-01

    Commelinid monocotyledons are a monophyletic clade differentiated from other monocotyledons by the presence of cell wall-bound ferulate and p-coumarate. The Poaceae, or grass family, is a member of this group, and most of the p-coumarate in the cell walls of this family acylates lignin. Here, we isolated and examined lignified cell wall preparations from 10 species of commelinid monocotyledons from nine families other than Poaceae, including species from all four commelinid monocotyledon orders (Poales, Zingiberales, Commelinales, and Arecales). We showed that, as in the Poaceae, lignin-linked p-coumarate occurs exclusively on the hydroxyl group on the γ-carbon of lignin unit side chains, mostly on syringyl units. Although the mechanism of acylation has not been studied directly in these species, it is likely to be similar to that in the Poaceae and involve BAHD acyl-coenzyme A:monolignol transferases. PMID:29724771

  3. Exploring the Leishmania Hydrophilic Acylated Surface Protein B (HASPB) Export Pathway by Live Cell Imaging Methods.

    MacLean, Lorna; Price, Helen; O'Toole, Peter

    2016-01-01

    Leishmania major is a human-infective protozoan parasite transmitted by the bite of the female phlebotomine sand fly. The L. major hydrophilic acylated surface protein B (HASPB) is only expressed in infective parasite stages suggesting a role in parasite virulence. HASPB is a "nonclassically" secreted protein that lacks a conventional signal peptide, reaching the cell surface by an alternative route to the classical ER-Golgi pathway. Instead HASPB trafficking to and exposure on the parasite plasma membrane requires dual N-terminal acylation. Here, we use live cell imaging methods to further explore this pathway allowing visualization of key events in real time at the individual cell level. These methods include live cell imaging using fluorescent reporters to determine the subcellular localization of wild type and acylation site mutation HASPB18-GFP fusion proteins, fluorescence recovery after photobleaching (FRAP) to analyze the dynamics of HASPB in live cells, and live antibody staining to detect surface exposure of HASPB by confocal microscopy.

  4. Synthesis of 1-isopropyl-3-acyl-5-methyl-benzimidazolone Derivatives and Their Antimicrobial Activity

    Shaopeng Wei

    2013-03-01

    Full Text Available A series of N-acylated analogues of 1-isopropyl-3-acyl-5-methyl-benzimidazolone were synthesized. Bioassay results indicated that analogues 5-07 and 5-19 exhibited the most potency against Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Analogues 5-02, 5-07, 5-12, 5-15, 5-19, 5-20 and 5-25 could effectively inhibit the spore germination of Botrytis cinerea. The relationship between structure and their antimicrobial activity (SAR has also been discussed according to aliphatic acids and aromatic acids derivatives, respectively. This implied that the N-acylated derivatives of 5-methyl-benzimidazolone might be potential antimicrobial agents.

  5. Phase behavior and nanoscale structure of phospholipid membranes incorporated with acylated C-14-peptides

    Pedersen, T.B.; Kaasgaard, Thomas; Jensen, M.O.

    2005-01-01

    The thermotropic phase behavior and lateral structure of dipalmitoylphosphatidylcholine (DPPC) lipid bilayers containing an acylated peptide has been characterized by differential scanning calorimetry (DSC) on vesicles and atomic force microscopy (AFM) on mica-supported bilayers. The acylated...... peptide, which is a synthetic decapeptide N-terminally linked to a C-14 acyl chain (C-14-peptide), is incorporated into DPPC bilayers in amounts ranging from 0-20 mol %. The calorimetric scans of the two-component system demonstrate a distinct influence of the C-14-peptide on the lipid bilayer...... gel phase DPPC bilayers, inserts preferentially into preexisting defect regions and has a noticeable influence on the organization of the surrounding lipids. The presence of the C-14-peptide gives rise to a laterally heterogeneous bilayer structure with coexisting lipid domains characterized by a 10...

  6. Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity.

    Ellis, Jessica M; Wong, G William; Wolfgang, Michael J

    2013-05-01

    Numerous neurological diseases are associated with dysregulated lipid metabolism; however, the basic metabolic control of fatty acid metabolism in neurons remains enigmatic. Here we have shown that neurons have abundant expression and activity of the long-chain cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase 7 (ACOT7) to regulate lipid retention and metabolism. Unbiased and targeted metabolomic analysis of fasted mice with a conditional knockout of ACOT7 in the nervous system, Acot7(N-/-), revealed increased fatty acid flux into multiple long-chain acyl-CoA-dependent pathways. The alterations in brain fatty acid metabolism were concomitant with a loss of lean mass, hypermetabolism, hepatic steatosis, dyslipidemia, and behavioral hyperexcitability in Acot7(N-/-) mice. These failures in adaptive energy metabolism are common in neurodegenerative diseases. In agreement, Acot7(N-/-) mice exhibit neurological dysfunction and neurodegeneration. These data show that ACOT7 counterregulates fatty acid metabolism in neurons and protects against neurotoxicity.

  7. Kinetics of acyl transfer reactions in organic media catalysed by Candida antarctica lipase B.

    Martinelle, M; Hult, K

    1995-09-06

    The acyl transfer reactions catalysed by Candida antartica lipase B in organic media followed a bi-bi ping-pong mechanism, with competitive substrate inhibition by the alcohols used as acyl acceptors. The effect of organic solvents on Vm and Km was investigated. The Vm values in acetonitrile was 40-50% of those in heptane. High Km values in acetonitrile compared to those in heptane could partly be explained by an increased solvation of the substrates in acetonitrile. Substrate solvation caused a 10-fold change in substrate specificity, defined as (Vm/Km)ethyl octanoate/(Vm/Km)octanoic acid, going from heptane to acetonitrile. Deacylation was the rate determining step for the acyl transfer in heptane with vinyl- and ethyl octanoate as acyl donors and (R)-2-octanol as acyl acceptor. With 1-octanol, a rate determining deacylation step in heptane was indicated using the same acyl donors. Using 1-octanol as acceptor in heptane, S-ethyl thiooctanoate had a 25- to 30-fold lower Vm/Km value and vinyl octanoate a 4-fold higher Vm/Km value than that for ethyl octanoate. The difference showed to be a Km effect for vinyl octanoate and mainly a Km effect for S-ethyl thiooctanoate. The Vm values of the esterification of octanoic acid with different alcohols was 10-30-times lower than those for the corresponding transesterification of ethyl octanoate. The low activity could be explained by a low pH around the enzyme caused by the acid or a withdrawing of active enzyme by nonproductive binding by the acid.

  8. N-Acylated and d Enantiomer Derivatives of a Nonamer Core Peptide of Lactoferricin B Showing Improved Antimicrobial Activity

    Wakabayashi, Hiroyuki; Matsumoto, Hiroshi; Hashimoto, Koichi; Teraguchi, Susumu; Takase, Mitsunori; Hayasawa, Hirotoshi

    1999-01-01

    N-acylated or d enantiomer peptide derivatives based on the sequence RRWQWRMKK in lactoferricin B demonstrated antimicrobial activities greater than those of lactoferricin B against bacteria and fungi. The most potent peptide, conjugated with an 11-carbon-chain acyl group, showed two to eight times lower MIC than lactoferricin B.

  9. N-Acylated and D enantiomer derivatives of a nonamer core peptide of lactoferricin B showing improved antimicrobial activity.

    Wakabayashi, H; Matsumoto, H; Hashimoto, K; Teraguchi, S; Takase, M; Hayasawa, H

    1999-05-01

    N-acylated or D enantiomer peptide derivatives based on the sequence RRWQWRMKK in lactoferricin B demonstrated antimicrobial activities greater than those of lactoferricin B against bacteria and fungi. The most potent peptide, conjugated with an 11-carbon-chain acyl group, showed two to eight times lower MIC than lactoferricin B.

  10. Continuous recording of long-chain acyl-coenzyme A synthetase activity using fluorescently labeled bovine serum albumin

    Demant, Erland J.F.; Nystrøm, Birthe T.

    2001-01-01

    acyl-Coenzyme A, synthetase, activity assay, fluorescence recording, fatty acid probe, serum albumin, hydroxycoumarin, detergent, micelles, Pseudomonas fragi, rat liver microsomes......acyl-Coenzyme A, synthetase, activity assay, fluorescence recording, fatty acid probe, serum albumin, hydroxycoumarin, detergent, micelles, Pseudomonas fragi, rat liver microsomes...

  11. Synthesis of 1-indanones through the intramolecular Friedel-Crafts acylation reaction using NbCl5 as Lewis acid

    Polo, Ellen Christine; Silva-Filho, Luiz Carlos da; Silva, Gil Valdo Jose da; Constantino, Mauricio Gomes

    2008-01-01

    The intramolecular Friedel-Crafts acylation reaction of 3-arylpropanoic acids to give 1-indanones can be effected in good yields under mild conditions (room temperature) by using niobium pentachloride. Our results indicate that NbCl 5 acts both as reagent (to transform carboxylic acids into acyl chlorides) and as catalyst in the Friedel-Crafts cyclization. (author)

  12. Acylation, Diastereoselective Alkylation, and Cleavage of an Oxazolidinone Chiral Auxiliary: A Multistep Asymmetric Synthesis Experiment for Advanced Undergraduates

    Smith, Thomas E.; Richardson, David P.; Truran, George A.; Belecki, Katherine; Onishi, Megumi

    2008-01-01

    An introduction to the concepts and experimental techniques of diastereoselective synthesis using a chiral auxiliary is described. The 4-benzyl-2-oxazolidinone chiral auxiliary developed by Evans is acylated with propionic anhydride under mild conditions using DMAP as an acyl transfer catalyst. Deprotonation with NaN(TMS)[subscript 2] at -78…

  13. 40 CFR 721.7270 - 1-propanaminium, 3-amino-, N,N,N-trimethyl-N-soya acyl derivs., chloride.

    2010-07-01

    ...-trimethyl-N-soya acyl derivs., chloride. 721.7270 Section 721.7270 Protection of Environment ENVIRONMENTAL...-soya acyl derivs., chloride. (a) Chemical substance and significant new uses subject to reporting. (1...., chloride (PMN P-01-646; CAS No. 391232-99-8) is subject to reporting under this section for the significant...

  14. Inhibition of 3T3-L1 adipocyte differentiation by expression of acyl-CoA-binding protein antisense RNA

    Mandrup, S; Sorensen, R V; Helledie, T

    1998-01-01

    Several lines of evidence have recently underscored the significance of fatty acids or fatty acid-derived metabolites as signaling molecules in adipocyte differentiation. The acyl-CoA-binding protein (ACBP), which functions as an intracellular acyl-CoA pool former and transporter, is induced duri...

  15. Reaction of tantalum-alkyne complexes with isocyanates or acyl cyanides

    Kataoka, Yasutaka; Oguchi, Yoshiyuki; Yoshizumi, Kazuyuki; Miwatashi, Seiji; Takai, Kazuhiko; Utimoto, Kiitiro

    1992-01-01

    Treatment of alkynes with low-valent tantalum derived from TiCl 5 and zinc produces tantalum-alkyne complexes (not isolated), which react in situ with phenyl isocyanate (or butyl isocyanate) to give (E)-α, β-unsaturated amides stereoselectively. The tantalum-alkyne complexes also react with acyl cyanides in the presence of BF 3 ·OEt 2 to give α-cyanohydrins. In both reactions, filtration of the reaction mixture containing the tantalum-alkyne complexes before addition of isocyanates (or acyl cyanides) is indispensable to obtain good yields. (author)

  16. pHP-Tethered N-Acyl Carbamate: A Photocage for Nicotinamide.

    Salahi, Farbod; Purohit, Vatsal; Ferraudi, Guillermo; Stauffacher, Cynthia; Wiest, Olaf; Helquist, Paul

    2018-05-04

    The synthesis of a new photocaged nicotinamide having an N-acyl carbamate linker and a p-hydroxyphenacyl (pHP) chromophore is described. The photophysical and photochemical studies showed an absorption maximum at λ = 330 nm and a quantum yield for release of 11% that are dependent upon both pH and solvent. While the acyl carbamate releases nicotinamide efficiently, a simpler amide linker was inert to photocleavage. This photocaged nicotinamide has significant advantages with respect to quantum yield, absorbance wavelength, rate of release, and solubility that make it the first practical example of a photocaged amide.

  17. Effect of room temperature ionic liquid structure on the enzymatic acylation of flavonoids

    Lue, Bena-Marie; Guo, Zheng; Xu, Xuebing

    2010-01-01

    Enzymatic acylation reactions of flavonoids (rutin, esculin) with long chain fatty acids (palmitic, oleic acids) were carried out in 14 different ionic liquid media containing a range of cation and anion structures. Classification of RTILs according to flavonoid solubility (using COSMO...... must be struck that maximized flavonoid solubility with minimum negative impact on lipase activity. The process also benefitted from an increased reaction temperature which may have helped to reduced mass transfer limitations. Keywords: Room temperature ionic liquids (RTILs); Biosynthesis; Acylation......; Flavonoids; Lipase; Long chain fatty acids...

  18. Synthesis of N-Acylated Amino Acid Surfactant from L-Proline and Palmitoyl Chloride

    Meutia Fadhilah Hasibuan; Mohd Wahid Samsudin; Rahimi Mohd Yusop; Suria Ramli

    2015-01-01

    A biodegradable, less toxic and environmentally friendly N-acylated amino acid surfactant was prepared from the amino acid L-proline and palmitoyl chloride through acylation reaction using the Schotten-Baumann reaction condition. The reaction result was a white flake form and the percentage of the crude yield was 72 % with melting point in range of 52 - 58 degree Celsius. Functional group of amide which was detected using Fourier Transform Infrared method showed the presence of N-palmitoyl proline. The purity analysis using High Performance Liquid Chromatography and Thin Layer Chromatography showed the result was a mixture compound. (author)

  19. Acyl-CoA binding proteins; structural and functional conservation over 2000 MYA

    Faergeman, Nils J; Wadum, Majken; Feddersen, Søren

    2007-01-01

    -CoA binding protein, ACBP, has been proposed to play a pivotal role in the intracellular trafficking and utilization of long-chain fatty acyl-CoA esters. Depletion of acyl-CoA binding protein in yeast results in aberrant organelle morphology incl. fragmented vacuoles, multi-layered plasma membranes...... and accumulation of vesicles of variable sizes. In contrast to synthesis and turn-over of glycerolipids, the levels of very-long-chain fatty acids, long-chain bases and ceramide are severely affected by Acb1p depletion, suggesting that Acb1p, rather than playing a general role, serves specific roles in cellular...

  20. Acyl-CoA-binding protein/diazepam-binding inhibitor gene and pseudogenes

    Mandrup, S; Hummel, R; Ravn, S

    1992-01-01

    Acyl-CoA-binding protein (ACBP) is a 10 kDa protein isolated from bovine liver by virtue of its ability to bind and induce the synthesis of medium-chain acyl-CoA esters. Surprisingly, it turned out to be identical to a protein named diazepam-binding Inhibitor (DBI) claimed to be an endogenous mod...... have molecularly cloned and characterized the ACBP/DBI gene family in rat. The rat ACBP/DBI gene family comprises one expressed gene and four processed pseudogenes of which one was shown to exist in two allelic forms. The expressed gene is organized into four exons and three introns...

  1. Selective Acylation Enhances Membrane Charge Sensitivity of the Antimicrobial Peptide Mastoparan-X

    Etzerodt, Thomas Povl; Henriksen, Jonas Rosager; Rasmussen, Palle

    2011-01-01

    and positioning of the peptide in the membrane caused by either PA or OA acylation play a critical role in the fine-tuning of the effective charge of the peptide and thereby the fine-tuning of the peptide's selectivity between neutral and negatively charged lipid membranes. This finding is unique compared...... to previous reports where peptide acylation enhanced membrane affinity but also resulted in impaired selectivity. Our result may provide a method of enhancing selectivity of antimicrobial peptides toward bacterial membranes due to their high negative charge—a finding that should be investigated for other...

  2. Association of acylated cationic decapeptides with dipalmitoylphosphatidylserine-dipalmitoyl- phosphatidylcholine lipid membranes

    Pedersen, T. B.; Sabra, Mads Christian; Frokjaer, Sven

    2001-01-01

    decapeptides that are N-terminally linked with C-2, C-8, and C-14 acyl chains contain four basic histidine residues in their identical amino acid sequence. A binding model, based on changes in the intrinsic fluorescent properties of the peptides upon association with the DPPC-DPPS membranes, is used...... DPPC-DPPS lipid mixture. The extent of peptide association deduced from the heat capacity measurements suggests a strong binding and membrane insertion of the C-14 acylated peptide in accordance with the fluorescence measurements....

  3. Des-Acyl Ghrelin and Ghrelin O-Acyltransferase Regulate Hypothalamic-Pituitary-Adrenal Axis Activation and Anxiety in Response to Acute Stress

    Stark, R.; Santos, V.V.; Geenen, B.; Cabral, A.; Dinan, T.; Bayliss, J.A.; Lockie, S.H.; Reichenbach, A.; Lemus, M.B.; Perello, M.; Spencer, S.J.; Kozicz, L.T.; Andrews, Z.B.

    2016-01-01

    Ghrelin exists in two forms in circulation, acyl ghrelin and des-acyl ghrelin, both of which have distinct and fundamental roles in a variety of physiological functions. Despite this fact, a large proportion of papers simply measure and refer to plasma ghrelin without specifying the acylation

  4. Acute aerobic exercise differentially alters acylated ghrelin and perceived fullness in normal-weight and obese individuals.

    Heden, Timothy D; Liu, Ying; Park, Youngmin; Dellsperger, Kevin C; Kanaley, Jill A

    2013-09-01

    Adiposity alters acylated ghrelin concentrations, but it is unknown whether adiposity alters the effect of exercise and feeding on acylated ghrelin responses. Therefore, the purpose of this study was to determine whether adiposity [normal-weight (NW) vs. obese (Ob)] influences the effect of exercise and feeding on acylated ghrelin, hunger, and fullness. Fourteen NW and 14 Ob individuals completed two trials in a randomized counterbalanced fashion, including a prior exercise trial (EX) and a no exercise trial (NoEX). During the EX trial, the participants performed 1 h of treadmill walking (55-60% peak O2 uptake) during the evening, 12 h before a 4-h standardized mixed meal test. Frequent blood samples were taken and analyzed for acylated ghrelin, and a visual analog scale was used to assess perceived hunger and fullness. In NW individuals, EX, compared with NoEX, reduced fasting acylated ghrelin concentrations by 18% (P = 0.03), and, in response to feeding, the change in acylated ghrelin (P = 0.02) was attenuated by 39%, but perceived hunger and fullness were unaltered. In Ob individuals, despite no changes in fasting or postprandial acylated ghrelin concentrations with EX, postprandial fullness was attenuated by 46% compared with NoEX (P = 0.05). In summary, exercise performed the night before a meal suppresses acylated ghrelin concentrations in NW individuals without altering perceived hunger or fullness. In Ob individuals, despite no changes in acylated ghrelin concentrations, EX reduced the fullness response to the test meal. Acylated ghrelin and perceived fullness responses are differently altered by acute aerobic exercise in NW and Ob individuals.

  5. In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine-based nanoparticles

    Lopes CDF

    2016-06-01

    Full Text Available Cátia DF Lopes,1–3,* Hugo Oliveira,1,* Inês Estevão,1 Liliana Raquel Pires,1 Ana Paula Pêgo1,2,4,5 1INEB – Instituto de Engenharia Biomédica, Universidade do Porto (UPorto, Porto, Portugal; 2i3S – Instituto de Investigação e Inovação em Saúde, NanoBiomaterials for Targeted Therapies Group, UPorto, Porto, Portugal; 3FMUP – Faculdade de Medicina da Universidade do Porto, Porto, Portugal; 4ICBAS – Instituto de Ciências Biomédicas Abel Salazar, UPorto, Porto, Portugal; 5FEUP – Faculdade de Engenharia da Universidade do Porto, Porto, Portugal *These authors contributed equally to this work Abstract: A major challenge in neuronal gene therapy is to achieve safe, efficient, and minimally invasive transgene delivery to neurons. In this study, we report the use of a nonviral neurotropic poly(ethylene imine-based nanoparticle that is capable of mediating neuron-specific transfection upon a subcutaneous injection. Nanoparticles were targeted to peripheral neurons by using the nontoxic carboxylic fragment of tetanus toxin (HC, which, besides being neurotropic, is capable of being retrogradely transported from neuron terminals to the cell bodies. Nontargeted particles and naked plasmid DNA were used as control. Five days after treatment by subcutaneous injection in the footpad of Wistar rats, it was observed that 56% and 64% of L4 and L5 dorsal root ganglia neurons, respectively, were expressing the reporter protein. The delivery mediated by HC-functionalized nanoparticles spatially limited the transgene expression, in comparison with the controls. Histological examination revealed no significant adverse effects in the use of the proposed delivery system. These findings demonstrate the feasibility and safety of the developed neurotropic nanoparticles for the minimally invasive delivery of genes to the peripheral nervous system, opening new avenues for the application of gene therapy strategies in the treatment of peripheral

  6. Diastereo- and regioselective addition of thioamide dianions to imines and aziridines: synthesis of N-thioacyl-1,2-diamines and N-thioacyl-1,3-diamines.

    Shibahara, Fumitoshi; Kobayashi, Shun-ichiro; Maruyama, Toshifumi; Murai, Toshiaki

    2013-01-02

    Addition reactions of thioamide dianions that were derived from N-arylmethyl thioamides to imines and aziridines were carried out. The reactions of imines gave the addition products of N-thioacyl-1,2-diamines in a highly diastereoselective manner in good-to-excellent yields. The diastereomeric purity of these N-thioacyl-1,2-diamines could be enriched by simple recrystallization. The reduction of N-thioacyl-1,2-diamines with LiAlH(4) gave their corresponding 1,2-diamines in moderate-to-good yields with retention of their stereochemistry. The oxidative-desulfurization/cyclization of an N-thioacyl-1,2-diamine in CuCl(2)/O(2) and I(2)/pyridine systems gave the cyclized product in moderate yield and the trans isomer was obtained as the sole product. On the other hand, a similar cyclization reaction with antiformin (aq. NaClO) as an oxidant gave the cis isomer as the major product. The reactions of N-tosylaziridines gave the addition products of N-thioacyl-1,3-diamines with low diastereoselectivity but high regioselectivity and in good-to-excellent yields. The use of AlMe(3) as an additive improved the efficiency and regioselectivity of the reaction. The stereochemistry of the obtained products was determined by X-ray diffraction. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Poly-Cross-Linked PEI Through Aromatically Conjugated Imine Linkages as a New Class of pH-Responsive Nucleic Acids Packing Cationic Polymers

    Chen, Shun; Jin, Tuo

    2016-01-01

    Cationic polyimines polymerized through aromatically conjugated bis-imine linkages and intra-molecular cross-linking were found to be a new class of effective transfection materials for their flexibility in structural optimization, responsiveness to intracellular environment, the ability to facilitate endosome escape and cytosol release of the nucleic acids, as well as self-metabolism. When three phthalaldehydes of different substitution positions were used to polymerize highly branched low-molecular weight polyethylenimine (PEI 1.8K), the product through ortho-phthalimines (named PPOP) showed significantly higher transfection activity than its two tere- and iso-analogs (named PPTP and PPIP). Physicochemical characterization confirmed the similarity of three polyimines in pH-responded degradability, buffer capacity, as well as the size and Zeta potential of the polyplexes formed from the polymers. A mechanistic speculation may be that the ortho-positioned bis-imine linkage of PPOP may only lead to the straight trans-configuration due to steric hindrance, resulting in larger loops of intra-polymer cross-linking and more flexible backbone. PMID:26869931

  8. Structural, kinetic, and docking studies of artificial imine reductases based on biotin-streptavidin technology: an induced lock-and-key hypothesis.

    Robles, Victor Muñoz; Dürrenberger, Marc; Heinisch, Tillmann; Lledós, Agustí; Schirmer, Tilman; Ward, Thomas R; Maréchal, Jean-Didier

    2014-11-05

    An artificial imine reductase results upon incorporation of a biotinylated Cp*Ir moiety (Cp* = C5Me5(-)) within homotetrameric streptavidin (Sav) (referred to as Cp*Ir(Biot-p-L)Cl] ⊂ Sav). Mutation of S112 reveals a marked effect of the Ir/streptavidin ratio on both the saturation kinetics as well as the enantioselectivity for the production of salsolidine. For [Cp*Ir(Biot-p-L)Cl] ⊂ S112A Sav, both the reaction rate and the selectivity (up to 96% ee (R)-salsolidine, kcat 14-4 min(-1) vs [Ir], KM 65-370 mM) decrease upon fully saturating all biotin binding sites (the ee varying between 96% ee and 45% ee R). In contrast, for [Cp*Ir(Biot-p-L)Cl] ⊂ S112K Sav, both the rate and the selectivity remain nearly constant upon varying the Ir/streptavidin ratio [up to 78% ee (S)-salsolidine, kcat 2.6 min(-1), KM 95 mM]. X-ray analysis complemented with docking studies highlight a marked preference of the S112A and S112K Sav mutants for the SIr and RIr enantiomeric forms of the cofactor, respectively. Combining both docking and saturation kinetic studies led to the formulation of an enantioselection mechanism relying on an "induced lock-and-key" hypothesis: the host protein dictates the configuration of the biotinylated Ir-cofactor which, in turn, by and large determines the enantioselectivity of the imine reductase.

  9. The role of ß-ketoacyl-acyl carrier protein synthase III in the condensation steps of fatty acid biosynthesis in sunflower

    González-Mellado, Damián; von Wettstein, Penny; Garcés, Rafael

    2010-01-01

    The ß-ketoacyl-acyl carrier protein synthase III (KAS III; EC 2.3.1.180) is a condensing enzyme catalyzing the initial step of fatty acid biosynthesis using acetyl-CoA as primer. To determine the mechanisms involved in the biosynthesis of fatty acids in sunflower (Helianthus annuus L.) developing...... seeds, a cDNA coding for HaKAS III (EF514400) was isolated, cloned and sequenced. Its protein sequence is as much as 72% identical to other KAS III-like ones such as those from Perilla frutescens, Jatropha curcas, Ricinus communis or Cuphea hookeriana. Phylogenetic study of the HaKAS III homologous...... proteins infers its origin from cyanobacterial ancestors. A genomic DNA gel blot analysis revealed that HaKAS III is a single copy gene. Expression levels of this gene, examined by Q-PCR, revealed higher levels in developing seeds storing oil than in leaves, stems, roots or seedling cotyledons...

  10. Ser/Thr Phosphorylation Regulates the Fatty Acyl-AMP Ligase Activity of FadD32, an Essential Enzyme in Mycolic Acid Biosynthesis*

    Le, Nguyen-Hung; Molle, Virginie; Eynard, Nathalie; Miras, Mathieu; Stella, Alexandre; Bardou, Fabienne; Galandrin, Ségolène; Guillet, Valérie; André-Leroux, Gwenaëlle; Bellinzoni, Marco; Alzari, Pedro; Mourey, Lionel; Burlet-Schiltz, Odile; Daffé, Mamadou; Marrakchi, Hedia

    2016-01-01

    Mycolic acids are essential components of the mycobacterial cell envelope, and their biosynthetic pathway is a well known source of antituberculous drug targets. Among the promising new targets in the pathway, FadD32 is an essential enzyme required for the activation of the long meromycolic chain of mycolic acids and is essential for mycobacterial growth. Following the in-depth biochemical, biophysical, and structural characterization of FadD32, we investigated its putative regulation via post-translational modifications. Comparison of the fatty acyl-AMP ligase activity between phosphorylated and dephosphorylated FadD32 isoforms showed that the native protein is phosphorylated by serine/threonine protein kinases and that this phosphorylation induced a significant loss of activity. Mass spectrometry analysis of the native protein confirmed the post-translational modifications and identified Thr-552 as the phosphosite. Phosphoablative and phosphomimetic FadD32 mutant proteins confirmed both the position and the importance of the modification and its correlation with the negative regulation of FadD32 activity. Investigation of the mycolic acid condensation reaction catalyzed by Pks13, involving FadD32 as a partner, showed that FadD32 phosphorylation also impacts the condensation activity. Altogether, our results bring to light FadD32 phosphorylation by serine/threonine protein kinases and its correlation with the enzyme-negative regulation, thus shedding a new horizon on the mycolic acid biosynthesis modulation and possible inhibition strategies for this promising drug target. PMID:27590338

  11. Bulk gold catalyzed oxidation reactions of amines and isocyanides and iron porphyrin catalyzed N-H and O-H bond insertion/cyclization reactions of diamines and aminoalcohols

    Klobukowski, Erik [Iowa State Univ., Ames, IA (United States)

    2011-01-01

    conditions, it was found that the oxidative dehydrogenation of dibenzylamine to Nbenzylidenebenzylamine, with N-methylmorpholine N-oxide (NMMO), was nearly quantitative (96%) within 24 h. However, the reaction with oxygen was much slower, with only a 52% yield of imine product over the same time period. Moreover, the rate of reaction was found to be influenced by the nature of the amine N-oxide. For example, the use of the weakly basic pyridine N-oxide (PyNO) led to an imine yield of only 6% after 24 h. A comparison of amine N-oxide and O2 was also examined in the oxidation of PhCH{sub 2}OH to PhCHO catalyzed by bulk gold. In this reaction, a 52% yield of the aldehyde was achieved when NMMO was used, while only a 7% product yield was afforded when O{sub 2} was the oxidant after 48 h. The bulk gold-catalyzed oxidative dehydrogenation of cyclic amines generates amidines, which upon treatment with Aerosil and water were found to undergo hydrolysis to produce lactams. Moreover, 5-, 6-, and 7-membered lactams could be prepared through a one-pot reaction of cyclic amines by treatment with oxygen, water, bulk gold, and Aerosil. This method is much more atom economical than industrial processes, does not require corrosive acids, and does not generate undesired byproducts. Additionally, the gold and Aerosil catalysts can be readily separated from the reaction mixture. The second project involved studying iron(III) tetraphenylporphyrin chloride, Fe(TPP)Cl, as a homogeneous catalyst for the generation of carbenes from diazo reagents and their reaction with heteroatom compounds. Fe(TPP)Cl, efficiently catalyzed the insertion of carbenes derived from methyl 2-phenyldiazoacetates into O-H bonds of aliphatic and aromatic alcohols. Fe(TPP)Cl was also found to be an effective catalyst for tandem N-H and O-H insertion/cyclization reactions when 1,2-diamines and 1,2-alcoholamines were treated with diazo reagents. This approach provides a one-pot process for synthesizing piperazinones and

  12. Checks and balances in membrane phospholipid class and acyl chain homeostasis, the yeast perspective

    de Kroon, A.I.P.M.|info:eu-repo/dai/nl/084765283; Rijken, P.J.|info:eu-repo/dai/nl/32716297X; De Smet, C.H.|info:eu-repo/dai/nl/304824224

    2013-01-01

    Glycerophospholipids are the most abundant membrane lipid constituents in most eukaryotic cells. As a consequence, phospholipid class and acyl chain homeostasis are crucial for maintaining optimal physical properties of membranes that in turn are crucial for membrane function. The topic of this

  13. 2-ethylhydracrylic aciduria in short/branched-chain acyl-CoA dehydrogenase deficiency

    Korman, Stanley H; Andresen, Brage S; Zeharia, Avraham

    2005-01-01

    BACKGROUND: Isolated excretion of 2-methylbutyrylglycine (2-MBG) is the hallmark of short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD), a recently identified defect in the proximal pathway of L-isoleucine oxidation. SBCADD might be underdiagnosed because detection and recognition...

  14. Catalytic Intermolecular Cross-Couplings of Azides and LUMO-Activated Unsaturated Acyl Azoliums

    Li, Wenjun

    2017-02-15

    An example for the catalytic synthesis of densely functionalized 1,2,3-triazoles through a LUMO activation mode has been developed. The protocol is enabled by intermolecular cross coupling reactions of azides with in situ-generated alpha,beta-unsaturated acyl azoliums. High yields and broad scope as well as the investigation of reaction mechanism are reported.

  15. New bradykinin analogues acylated on the N-terminus: effect on rat uterus and blood pressure

    Labudda, O.; Wierzba, T.; Sobolewski, D.; Sleszyňska, M.; Gawiňski, L.; Plačková, Malgorzata; Slaninová, Jiřina; Prahl, A.

    2007-01-01

    Roč. 54, č. 1 (2007), s. 193-198 ISSN 0001-527X Grant - others:State Comittee for Scientific Research(PL) PB1108/T09/2005/28 Institutional research plan: CEZ:AV0Z40550506 Keywords : bradykinin * antagonists * acylation Subject RIV: CE - Biochemistry Impact factor: 1.261, year: 2007 www.actabp.pl

  16. In vitro and in vivo aspects of N-acyl-phosphatidylethanolamine-containing liposomes

    Vermehren, C.; Clausen-Beck, B.; Frøkjær, S.

    2003-01-01

    Incorporation of the phospholipid, N-acyl-phosphatidylethanolamine (NAPE), has shown to increase the liposomal stability towards plasma components in vitro. Besides increasing the circulation-time, NAPE has been shown to contain fusiogenic properties. Hence, fusion between NAPE-liposomes and target...

  17. Antipathogenic potential of marine Bacillus sp. SS4 on N-acyl ...

    Antipathogenic therapy is an outcome of the quorum-sensing inhibition (QSI) mechanism, which targets autoinducer-dependent virulent gene expression in bacterial pathogens. -acyl homoserine lactone (AHL) acts as a key regulator in the production of virulence factors and biofilm formation in Pseudomonas aeruginosa ...

  18. N-acyl thioureas - selective ligands for complexing of heavy metals and noble metals

    Schuster, M.

    1992-01-01

    Acyl thioureas are complexing agents for heavy metals that are easily produced and very stable. Their favourable toxicological data make them particularly suitable for industrial applications, e.g. detoxification of metallic process solutions or solvent extraction of metals. (orig.) [de

  19. Tissue carnitine homeostasis in very-long-chain acyl-CoA dehydrogenase-deficient mice

    Spiekerkoetter, Ute; Tokunaga, Chonan; Wendel, Udo; Mayatepek, Ertan; Ijlst, Lodewijk; Vaz, Frederic M.; van Vlies, Naomi; Overmars, Henk; Duran, Marinus; Wijburg, Frits A.; Wanders, Ronald J.; Strauss, Arnold W.

    2005-01-01

    Deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD) is the most common long-chain fatty acid oxidation defect and presents with heterogeneous clinical manifestations. Accumulation of long-chain acylcarnitines and deficiency of free carnitine have often been proposed to play an important

  20. Selective Monoacylation of Ferrocene with Bulky Acylating Agents over Mesoporous Sieve AlKIT-5

    Vitvarová, Dana; Voláková, Martina; Vlk, Josef; Vinu, A.; Štěpnička, P.; Čejka, Jiří

    2010-01-01

    Roč. 16, č. 26 (2010), s. 7773-7780 ISSN 0947-6539 R&D Projects: GA ČR GA104/07/0383; GA ČR GD203/08/H032 Institutional research plan: CEZ:AV0Z40400503 Keywords : acylation * aluminum * ferrocene Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.476, year: 2010

  1. New cardenolide and acylated lignan glycosides from the aerial parts of Asclepias curassavica.

    Warashina, Tsutomu; Shikata, Kimiko; Miyase, Toshio; Fujii, Satoshi; Noro, Tadataka

    2008-08-01

    Three new cardenolide glycosides and six new acylated lignan glycosides were obtained along with nineteen known compounds from the aerial parts of Asclepias curassavica L. (Asclepiadaceae). The structure of each compound was determined based on interpretations of NMR and MS measurements and chemical evidence.

  2. Endotoxin Structures in the Psychrophiles Psychromonas marina and Psychrobacter cryohalolentis Contain Distinctive Acyl Features

    Charles R. Sweet

    2014-07-01

    Full Text Available Lipid A is the essential component of endotoxin (Gram-negative lipopolysaccharide, a potent immunostimulatory compound. As the outer surface of the outer membrane, the details of lipid A structure are crucial not only to bacterial pathogenesis but also to membrane integrity. This work characterizes the structure of lipid A in two psychrophiles, Psychromonas marina and Psychrobacter cryohalolentis, and also two mesophiles to which they are related using MALDI-TOF MS and fatty acid methyl ester (FAME GC-MS. P. marina lipid A is strikingly similar to that of Escherichia coli in organization and total acyl size, but incorporates an unusual doubly unsaturated tetradecadienoyl acyl residue. P. cryohalolentis also shows structural organization similar to a closely related mesophile, Acinetobacter baumannii, however it has generally shorter acyl constituents and shows many acyl variants differing by single methylene (-CH2- units, a characteristic it shares with the one previously reported psychrotolerant lipid A structure. This work is the first detailed structural characterization of lipid A from an obligate psychrophile and the second from a psychrotolerant species. It reveals distinctive structural features of psychrophilic lipid A in comparison to that of related mesophiles which suggest constitutive adaptations to maintain outer membrane fluidity in cold environments.

  3. Clinical aspects of short-chain acyl-CoA dehydrogenase deficiency

    Maldegem, B.T.; Wanders, R.J.A.; Wijburg, F.A.

    2010-01-01

    Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation. SCADD is biochemically characterized by increased C4-carnitine in plasma and ethylmalonic acid in urine. The diagnosis of SCADD is confirmed by DNA analysis showing

  4. Purification of peroxisomal acyl-CoA: dihydroxyacetonephosphate acyltransferase from human placenta

    Ofman, R.; Wanders, R. J.

    1994-01-01

    The peroxisomal enzyme acyl-CoA:dihydroxyacetonephosphate acyltransferase (DHAPAT) was extracted from human placental membranes using CHAPS as a detergent in the presence of 1 M KCl. Prior to assay dipalmitoylphosphatidylcholine was added to the sample as eluted from the various columns in order to

  5. Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset

    Smelt, A H; Poorthuis, B J; Onkenhout, W

    1998-01-01

    Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9), tetrade......Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9......), tetradecadienoic acid, 14:2(n-6), and hexadecadienoic acid, 16:2(n-6). Palmitoyl-CoA and behenoyl-CoA dehydrogenase in fibroblasts were deficient. Muscle VLCAD activity was very low. DNA analysis revealed compound heterozygosity for two missense mutations in the VLCAD gene. The relatively mild clinical course may...... be due to residual enzyme activity as a consequence of the two missense mutations. Treatment with L-carnitine and medium chain triglycerides in the diet did not reduce the attacks of rhabdomyolysis....

  6. Alkylation of phenols and acylation 2-methoxynaphthalene over SSZ-33, SSZ-35 and SSZ-42 zeolites

    Vitvarová, Dana; Lupínková, Lenka; Kubů, Martin

    2015-01-01

    Roč. 210, JUL 2015 (2015), s. 133-141 ISSN 1387-1811 R&D Projects: GA ČR GAP106/11/0819 Institutional support: RVO:61388955 Keywords : phenol alkylation * 2-methoxynaphthalene acylation * SSZ-33 Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.349, year: 2015

  7. Lysine sulfonamides as novel HIV-protease inhibitors: Nepsilon-acyl aromatic alpha-amino acids.

    Stranix, Brent R; Lavallée, Jean-François; Sévigny, Guy; Yelle, Jocelyn; Perron, Valérie; LeBerre, Nicholas; Herbart, Dominik; Wu, Jinzi J

    2006-07-01

    A series of lysine sulfonamide analogues bearing Nepsilon-acyl aromatic amino acids were synthesized using an efficient synthetic route. Evaluation of these novel protease inhibitors revealed compounds with high potency against wild-type and multiple-protease inhibitor-resistant HIV viruses.

  8. Synthesis of acetylene alcohols of heterocyclic type and the acyl derivatives

    Moldir Dyusebaeva

    2015-03-01

    Full Text Available A synthesis of potentially biologically active heterocyclic amino alcohols of acetylene (Piperidine and Morpholine under the conditions of Mannich reaction accomplished and received their acyl derivatives. Pharmacological activity (antibacterial and antispasmotic of synthesized compounds, also acute toxicological characteristics studied. The study showed that the combination of DMAE-4 has antispasmodic activity with low toxicity.

  9. A Rational Approach to Identify Inhibitors of Mycobacterium tuberculosis Enoyl Acyl Carrier Protein Reductase

    Chhabria, M. T.; Parmar, K. B.; Brahmkshatriya, Pathik

    2013-01-01

    Roč. 19, č. 21 (2013), s. 3878-3883 ISSN 1381-6128 Institutional support: RVO:61388963 Keywords : mycobacterium tuberculosis * enoyl acyl carrier protein reductase * pharmacophore modeling * molecular docking * binding interactions Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.288, year: 2013

  10. Application of an Acyl-CoA Ligase from Streptomyces aizunensis for Lactam Biosynthesis

    Zhang, Jingwei; Barajas, Jesus F.; Burdu, Mehmet

    2017-01-01

    lactams under ambient conditions. In this study, we demonstrated production of these chemicals using ORF26, an acyl-CoA ligase involved in the biosynthesis of ECO-02301 in Streptomyces aizunensis. This enzyme has a broad substrate spectrum and can cyclize 4-aminobutyric acid into γ-butyrolactam, 5...

  11. Quorum quenching by an N-acyl-homoserine lactone acylase from Pseudomonas aeruginosa PAO1

    Sio, CF; Otten, LG; Cool, RH; Diggle, SP; Braun, PG; Daykin, M; Camara, M; Williams, P; Quax, WJ; Bos, R

    The virulence of the opportunistic human pathogen Pseudomonas aeruginosa PAO1 is controlled by an N-acyl-homoserine lactone (AHL)-dependent quorum-sensing system. During functional analysis of putative acylase genes in the P. aeruginosa PAO1 genome, the PA2385 gene was found to encode an acylase

  12. Improved Synthesis of 1-O-Acyl-β-d-Glucopyranose Tetraacetates

    Yu Chen

    2017-04-01

    Full Text Available An improved synthesis of 1-O-acyl glucosyl esters that avoids the use of expensive Ag reagents as well as the hydrolysis of unstable glucosyl bromides is reported. Notably, β-configuration products were obtained exclusively in good yields.

  13. Acylation of aromatic alcohols and phenols over InCl3 ...

    Unknown

    toluene sulphonic acid,5 ZnCl2,6 COCl2,7 Sc(OTf)3. 8 or Bi(OTf)3. 9] catalyst ... tion of benzene and other aromatic compounds.12,13. In this communication, we ... val of solvent from the reaction mixture by distillation. The acylated products ...

  14. Homochiral Acyl Isocyanates as Diagnostic NMR Probes for the Enantiomeric Purity of Chiral Alcohols

    Gregory H. P. Roos

    2000-12-01

    Full Text Available The first reported acyl and sulfonylisocyanates were developed and tested in reactions with chiral alcohols to afford diastereomeric carbamates. NMR analysis of these investigates the chemical shift discrimination that would allow these activated isocyanates to be used as diagnostic probes of enantiomeric purity.

  15. Acyl-CoA binding protein is an essential protein in mammalian cell lines

    Knudsen, Jens; Færgeman, Nils J.

    2002-01-01

    In the present work, small interference RNA was used to knock-down acyl-CoA binding protein (ACBP) in HeLa, HepG2 and Chang cells. Transfection with ACBP-specific siRNA stopped growth, detached cells from the growth surface and blocked thymidine and acetate incorporation. The results show...

  16. Iodine-Catalyzed Isomerization of Dimethyl Muconate

    Settle, Amy E [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Berstis, Laura R [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Zhang, Shuting [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Rorrer, Nicholas [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Hu, Haiming [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Richards, Ryan [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Beckham, Gregg T [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Crowley, Michael F [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Vardon, Derek R [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2018-04-12

    cis,cis-Muconic acid is a platform biobased chemical that can be upgraded to drop-in commodity and novel monomers. Among the possible drop-in products, dimethyl terephthalate can be synthesized via esterification, isomerization, Diels-Alder cycloaddition, and dehydrogenation. The isomerization of cis,cis-dimethyl muconate (ccDMM) to the trans,trans-form (ttDMM) can be catalyzed by iodine; however, studies have yet to address (i) the mechanism and reaction barriers unique to DMM, and (ii) the influence of solvent, potential for catalyst recycle, and recovery of high-purity ttDMM. To address this gap, we apply a joint computational and experimental approach to investigate iodine-catalyzed isomerization of DMM. Density functional theory calculations identified unique regiochemical considerations due to the large number of halogen-diene coordination schemes. Both transition state theory and experiments estimate significant barrier reductions with photodissociated iodine. Solvent selection was critical for rapid kinetics, likely due to solvent complexation with iodine. Under select conditions, ttDMM yields of 95% were achieved in <1 h with methanol, followed by high purity recovery (>98%) with crystallization. Lastly, post-reaction iodine can be recovered and recycled with minimal loss of activity. Overall, these findings provide new insight into the mechanism and conditions necessary for DMM isomerization with iodine to advance the state-of-the-art for biobased chemicals.

  17. Manganese Catalyzed C–H Halogenation

    Liu, Wei; Groves, John T.

    2015-06-16

    The remarkable aliphatic C–H hydroxylations catalyzed by the heme-containing enzyme, cytochrome P450, have attracted sustained attention for more than four decades. The effectiveness of P450 enzymes as highly selective biocatalysts for a wide range of oxygenation reactions of complex substrates has driven chemists to develop synthetic metalloporphyrin model compounds that mimic P450 reactivity. Among various known metalloporphyrins, manganese derivatives have received considerable attention since they have been shown to be versatile and powerful mediators for alkane hydroxylation and olefin epoxidation. Mechanistic studies have shown that the key intermediates of the manganese porphyrin-catalyzed oxygenation reactions include oxo- and dioxomanganese(V) species that transfer an oxygen atom to the substrate through a hydrogen abstraction/oxygen recombination pathway known as the oxygen rebound mechanism. Application of manganese porphyrins has been largely restricted to catalysis of oxygenation reactions until recently, however, due to ultrafast oxygen transfer rates. In this Account, we discuss recently developed carbon–halogen bond formation, including fluorination reactions catalyzed by manganese porphyrins and related salen species. We found that biphasic sodium hypochlorite/manganese porphyrin systems can efficiently and selectively convert even unactivated aliphatic C–H bonds to C–Cl bonds. An understanding of this novel reactivity derived from results obtained for the oxidation of the mechanistically diagnostic substrate and radical clock, norcarane. Significantly, the oxygen rebound rate in Mn-mediated hydroxylation is highly correlated with the nature of the trans-axial ligands bound to the manganese center (L–MnV$=$O). Based on the ability of fluoride ion to decelerate the oxygen rebound step, we envisaged that a relatively long-lived substrate radical could be trapped by a Mn–F fluorine source, effecting carbon–fluorine bond

  18. Structural and Functional Studies of Fatty Acyl Adenylate Ligases from E. coli and L. pneumophila

    Zhang, Z.; Swaminathan, S.; Zhou, R.; Sauder, J. M.; Tonge, P. J.; Burley, S. K.

    2011-02-18

    Fatty acyl-AMP ligase (FAAL) is a new member of a family of adenylate-forming enzymes that were recently discovered in Mycobacterium tuberculosis. They are similar in sequence to fatty acyl-coenzyme A (CoA) ligases (FACLs). However, while FACLs perform a two-step catalytic reaction, AMP ligation followed by CoA ligation using ATP and CoA as cofactors, FAALs produce only the acyl adenylate and are unable to perform the second step. We report X-ray crystal structures of full-length FAAL from Escherichia coli (EcFAAL) and FAAL from Legionella pneumophila (LpFAAL) bound to acyl adenylate, determined at resolution limits of 3.0 and 1.85 {angstrom}, respectively. The structures share a larger N-terminal domain and a smaller C-terminal domain, which together resemble the previously determined structures of FAAL and FACL proteins. Our two structures occur in quite different conformations. EcFAAL adopts the adenylate-forming conformation typical of FACLs, whereas LpFAAL exhibits a unique intermediate conformation. Both EcFAAL and LpFAAL have insertion motifs that distinguish them from the FACLs. Structures of EcFAAL and LpFAAL reveal detailed interactions between this insertion motif and the interdomain hinge region and with the C-terminal domain. We suggest that the insertion motifs support sufficient interdomain motions to allow substrate binding and product release during acyl adenylate formation, but they preclude CoA binding, thereby preventing CoA ligation.

  19. Diclofenac degradation in water by FeCeOx catalyzed H2O2: Influencing factors, mechanism and pathways.

    Chong, Shan; Zhang, Guangming; Zhang, Nan; Liu, Yucan; Huang, Ting; Chang, Huazhen

    2017-07-15

    The degradation of diclofenac in a like Fenton system, FeCeO x -H 2 O 2 , was studied in details. The influencing factors, reaction kinetics, reaction mechanism and degradation pathways of diclofenac were investigated. The optimum conditions were at a solution pH of 5.0, H 2 O 2 concentration of 3.0mmol/L, diclofenac initial concentration of 0.07mmol/L, FeCeO x dosage of 0.5g/L, and 84% degradation of diclofenac was achieved within 40min. The kinetics of FeCeO x catalyzed H 2 O 2 process involved adsorption-dominating and degradation-dominating stages and fitted pseudo-second order model and pseudo-first order model, respectively. Singlet oxygen 1 O 2 was the primary intermediate oxidative species in the degradation process; superoxide radical anion O 2 - also participated in the reaction. The surface cerium and iron sites and the oxygen vacancies in the FeCeO x catalyst were proposed to play an important role in H 2 O 2 decomposition and active species generation. The detected intermediates were identified as hydroxylated derivatives (m/z of 310, 326 and 298), quinone imine compounds (m/z of 308, 278 and 264) and hydroxyl phenylamine (m/z of 178). The majority intermediates were hydroxylated derivatives and the minority was hydroxyl phenylamine. The degradation pathways were proposed to involve hydroxylation, decarboxylation, dehydrogenation and CN bond cleavage. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Binding of acyl CoA by fatty acid binding protein and the effect on fatty acid activation

    Burrier, R.E.; Manson, C.R.; Brecher, P.

    1987-01-01

    The ability of purified rat liver and heart fatty acid binding proteins (FABPs) to bind oleoyl CoA and modulate acyl CoA synthesis by microsomal membranes was investigated. Using binding assays employing either Lipidex 1000 or multilamellar liposomes to sequester unbound ligand, rat liver but not rat heart FABP was shown to bind radiolabeled acyl CoA. Binding studies suggest that liver FABP has a single binding site for acyl CoA which is separate from the two binding sites for fatty acids. Experiments were then performed to determine how binding may influence acyl CoA metabolism by liver microsomes or heart sarcoplasmic reticulum. Using liposomes as fatty acid donors, liver FABP stimulated acyl CoA production whereas heart FABP did not stimulate production over control values. 14 C-Fatty acid-FABP complexes were prepared, incubated with membranes and acyl CoA synthetase activity was determined. Up to 70% of the fatty acid could be converted to acyl CoA in the presence of liver FABP but in the presence of heart FABP, only 45% of the fatty acid was converted. The amount of product formed was not changed by additional membrane, enzyme cofactor, or incubation time. Liver but not heart FABP bound the acyl CoA formed and removed it from the membranes. These studies suggest that liver FABP can increase the amount of acyl CoA by binding this ligand thereby removing it from the membrane and possibly aiding transport within the cell

  1. Binding of acyl CoA by fatty acid binding protein and the effect on fatty acid activation

    Burrier, R.E.; Manson, C.R.; Brecher, P.

    1987-05-01

    The ability of purified rat liver and heart fatty acid binding proteins (FABPs) to bind oleoyl CoA and modulate acyl CoA synthesis by microsomal membranes was investigated. Using binding assays employing either Lipidex 1000 or multilamellar liposomes to sequester unbound ligand, rat liver but not rat heart FABP was shown to bind radiolabeled acyl CoA. Binding studies suggest that liver FABP has a single binding site for acyl CoA which is separate from the two binding sites for fatty acids. Experiments were then performed to determine how binding may influence acyl CoA metabolism by liver microsomes or heart sarcoplasmic reticulum. Using liposomes as fatty acid donors, liver FABP stimulated acyl CoA production whereas heart FABP did not stimulate production over control values. /sup 14/C-Fatty acid-FABP complexes were prepared, incubated with membranes and acyl CoA synthetase activity was determined. Up to 70% of the fatty acid could be converted to acyl CoA in the presence of liver FABP but in the presence of heart FABP, only 45% of the fatty acid was converted. The amount of product formed was not changed by additional membrane, enzyme cofactor, or incubation time. Liver but not heart FABP bound the acyl CoA formed and removed it from the membranes. These studies suggest that liver FABP can increase the amount of acyl CoA by binding this ligand thereby removing it from the membrane and possibly aiding transport within the cell.

  2. The polymerisation of oligo(ethylene glycol methyl ether) methacrylate from a multifunctional poly(ethylene imine) derived amide : a stabiliser for the synthesis and dispersion of magnetite nanoparticles

    Kleine, A.; Altan, C.L.; Yarar, U.E.; Sommerdijk, N.A.J.M.; Bucak, S.; Holder, S.J.

    2014-01-01

    A facile synthetic route to poly(ethylene imine)-graft-poly(oligo(ethylene glycol methyl ether)) (PEI-graft-POEGMA) functionalised superparamagnetic magnetite nanoparticles is described. The polymerisation of OEGMA from a model molecular amide demonstrated the feasibility of POEGMA synthesis under

  3. S-acylation of SOD1, CCS, and a stable SOD1-CCS heterodimer in human spinal cords from ALS and non-ALS subjects.

    Antinone, Sarah E; Ghadge, Ghanashyam D; Ostrow, Lyle W; Roos, Raymond P; Green, William N

    2017-01-25

    Previously, we found that human Cu, Zn-superoxide dismutase (SOD1) is S-acylated (palmitoylated) in vitro and in amyotrophic lateral sclerosis (ALS) mouse models, and that S-acylation increased for ALS-causing SOD1 mutants relative to wild type. Here, we use the acyl resin-assisted capture (acyl-RAC) assay to demonstrate S-acylation of SOD1 in human post-mortem spinal cord homogenates from ALS and non-ALS subjects. Acyl-RAC further revealed that endogenous copper chaperone for SOD1 (CCS) is S-acylated in both human and mouse spinal cords, and in vitro in HEK293 cells. SOD1 and CCS formed a highly stable heterodimer in human spinal cord homogenates that was resistant to dissociation by boiling, denaturants, or reducing agents and was not observed in vitro unless both SOD1 and CCS were overexpressed. Cysteine mutations that attenuate SOD1 maturation prevented the SOD1-CCS heterodimer formation. The degree of S-acylation was highest for SOD1-CCS heterodimers, intermediate for CCS monomers, and lowest for SOD1 monomers. Given that S-acylation facilitates anchoring of soluble proteins to cell membranes, our findings suggest that S-acylation and membrane localization may play an important role in CCS-mediated SOD1 maturation. Furthermore, the highly stable S-acylated SOD1-CCS heterodimer may serve as a long-lived maturation intermediate in human spinal cord.

  4. S-naproxen-ss-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-H-1 NMR and high-performance liquid chromatography-UV

    Mortensen, R. W.; Corcoran, O.; Cornett, Claus

    2001-01-01

    Acyl-migrated isomers of drug beta -1-O-acyl glucuronides have been implicated in drug toxicity because they can bind to proteins. The acyl migration and hydrolysis of S-naproxen-beta -1-O-acyl glucuronide (S-nap-g) was followed by dynamic stopped-flow HPLC-H-1 NMR and HPLC methods. Nine first or...

  5. Representing Rate Equations for Enzyme-Catalyzed Reactions

    Ault, Addison

    2011-01-01

    Rate equations for enzyme-catalyzed reactions are derived and presented in a way that makes it easier for the nonspecialist to see how the rate of an enzyme-catalyzed reaction depends upon kinetic constants and concentrations. This is done with distribution equations that show how the rate of the reaction depends upon the relative quantities of…

  6. Enhanced visible-light photocatalytic activity for selective oxidation of amines into imines over TiO{sub 2}(B)/anatase mixed-phase nanowires

    Dai, Jun [Institute of Applied Chemistry, Henan Polytechnic University, Jiaozuo 454003 (China); State Key Laboratory Cultivation Base for Gas Geology and Gas Control, School of Safety Science and Engineering, Henan Polytechnic University, Jiaozuo 454003 (China); Yang, Juan, E-mail: yangjuanhpu@yahoo.com [Institute of Applied Chemistry, Henan Polytechnic University, Jiaozuo 454003 (China); Wang, Xiaohan; Zhang, Lei; Li, Yingjie [Institute of Applied Chemistry, Henan Polytechnic University, Jiaozuo 454003 (China)

    2015-09-15

    Graphical abstract: Visible-light photocatalytic activities for selective oxidation of amines into imines are greatly affected by the crystal structure of TiO{sub 2} catalysts and mixed-phase TiO{sub 2}(B)/anatase possess higher photoactivity because of the moderate adsorption ability and efficient charge separation. - Highlights: • Visible-light photocatalytic oxidation of amines to imines is studied over different TiO{sub 2}. • Photocatalytic activities are greatly affected by the crystal structure of TiO{sub 2} nanowires. • Mixed-phase TiO{sub 2}(B)/anatase exhibits higher catalytic activity than single-phase TiO{sub 2}. • Enhanced activity is ascribed to efficient adsorption ability and interfacial charge separation. • Photoinduced charge transfer mechanism on TiO{sub 2}(B)/anatase catalysts is also proposed. - Abstract: Wirelike catalysts of mixed-phase TiO{sub 2}(B)/anatase TiO{sub 2}, bare anatase TiO{sub 2} and TiO{sub 2}(B) are synthesized via calcining precursor hydrogen titanate obtained from hydrothermal process at different temperatures between 450 and 700 °C. Under visible light irradiation, mixed-phase TiO{sub 2}(B)/anatase TiO{sub 2} catalysts exhibit enhanced photocatalytic activity in comparison with pure TiO{sub 2}(B) and anatase TiO{sub 2} toward selective oxidation of benzylamines into imines and the highest photocatalytic activity is achieved by TW-550 sample consisting of 65% TiO{sub 2}(B) and 35% anatase. The difference in photocatalytic activities of TiO{sub 2} samples can be attributed to the different adsorption abilities resulted from their crystal structures and interfacial charge separation driven by surface-phase junctions between TiO{sub 2}(B) and anatase TiO{sub 2}. Moreover, the photoinduced charge transfer mechanism of surface complex is also proposed over mixed-phase TiO{sub 2}(B)/anatase TiO{sub 2} catalysts. Advantages of this photocatalytic system include efficient utilization of solar light, general suitability to

  7. Enhanced visible-light photocatalytic activity for selective oxidation of amines into imines over TiO2(B)/anatase mixed-phase nanowires

    Dai, Jun; Yang, Juan; Wang, Xiaohan; Zhang, Lei; Li, Yingjie

    2015-01-01

    Graphical abstract: Visible-light photocatalytic activities for selective oxidation of amines into imines are greatly affected by the crystal structure of TiO 2 catalysts and mixed-phase TiO 2 (B)/anatase possess higher photoactivity because of the moderate adsorption ability and efficient charge separation. - Highlights: • Visible-light photocatalytic oxidation of amines to imines is studied over different TiO 2 . • Photocatalytic activities are greatly affected by the crystal structure of TiO 2 nanowires. • Mixed-phase TiO 2 (B)/anatase exhibits higher catalytic activity than single-phase TiO 2 . • Enhanced activity is ascribed to efficient adsorption ability and interfacial charge separation. • Photoinduced charge transfer mechanism on TiO 2 (B)/anatase catalysts is also proposed. - Abstract: Wirelike catalysts of mixed-phase TiO 2 (B)/anatase TiO 2 , bare anatase TiO 2 and TiO 2 (B) are synthesized via calcining precursor hydrogen titanate obtained from hydrothermal process at different temperatures between 450 and 700 °C. Under visible light irradiation, mixed-phase TiO 2 (B)/anatase TiO 2 catalysts exhibit enhanced photocatalytic activity in comparison with pure TiO 2 (B) and anatase TiO 2 toward selective oxidation of benzylamines into imines and the highest photocatalytic activity is achieved by TW-550 sample consisting of 65% TiO 2 (B) and 35% anatase. The difference in photocatalytic activities of TiO 2 samples can be attributed to the different adsorption abilities resulted from their crystal structures and interfacial charge separation driven by surface-phase junctions between TiO 2 (B) and anatase TiO 2 . Moreover, the photoinduced charge transfer mechanism of surface complex is also proposed over mixed-phase TiO 2 (B)/anatase TiO 2 catalysts. Advantages of this photocatalytic system include efficient utilization of solar light, general suitability to amines, reusability and facile separation of nanowires catalysts

  8. Molecular Characterization of Two Lysophospholipid:acyl-CoA Acyltransferases Belonging to the MBOAT Family in Nicotiana benthamiana.

    Donghui Zhang

    Full Text Available In the remodeling pathway for the synthesis of phosphatidylcholine (PC, acyl-CoA-dependent lysophosphatidylcholine (lysoPC acyltransferase (LPCAT catalyzes the reacylation of lysoPC. A number of genes encoding LPCATs have been cloned and characterized from several plants in recent years. Using Arabidopsis and other plant LPCAT sequences to screen the genome database of Nicotiana benthamiana, we identified two cDNAs encoding the putative tobacco LPCATs (NbLPCAT1 and NbLPCAT2. Both of them were predicted to encode a protein of 463 amino acids with high similarity to LPCATs from other plants. Protein sequence features such as the presence of at least eight putative transmembrane regions, four highly conserved signature motifs and several invariant residues indicate that NbLPCATs belong to the membrane bound O-acyltransferase family. Lysophospholipid acyltransferase activity of NbLPCATs was confirmed by testing lyso-platelet-activating factor (lysoPAF sensitivity through heterologous expression of each full-length cDNA in a yeast mutant Y02431 (lca1△ disrupted in endogenous LPCAT enzyme activity. Analysis of fatty acid profiles of phospholipids from the NbLPCAT-expressing yeast mutant Y02431 cultures supplemented with polyunsaturated fatty acids suggested more incorporation of linoleic acid (18:2n6, LA and α-linolenic acid (18:3n3, ALA into PC compared to yeast mutant harbouring empty vector. In vitro enzymatic assay demonstrated that NbLPCAT1had high lysoPC acyltransferase activity with a clear preference for α-linolenoyl-CoA (18:3, while NbLPCAT2 showed a high lysophosphatidic acid (lysoPA acyltransferase activity towards α-linolenoyl-CoA and a weak lysoPC acyltransferase activity. Tissue-specific expression analysis showed a ubiquitous expression of NbLPCAT1 and NbLPCAT2 in roots, stems, leaves, flowers and seeds, and a strong expression in developing flowers. This is the first report on the cloning and characterization of lysophospholipid

  9. Theoretical survey of muon catalyzed fusion

    Leon, M.

    1988-01-01

    The main steps in the muon-catalyzed d-t fusion cycle are given in this report. Most of the stages are very fast, and therefore do not contribute significantly to the cycling time. Thus at liquid H 2 densities (/phi/ = 1 in the standard convention) the time for stopping the negative muon, its subsequent capture and deexcitation to the ground state is estimated to be /approximately/ 10/sup/minus/11/ sec. 1 The muon spends essentially all of its time in either the (dμ) ground state, waiting for transfer to a (tμ) ground state to occur, or in the (tμ) ground state, writing for molecular formation to occur. Following the formation of this ''mesomolecule'' (actually a muonic molecular ion), deexcitation and fusion are again fast. Then the muon is (usually) liberated to go around again. We will discuss these steps in some detail. 5 refs., 3 figs

  10. Heterogeneously Catalyzed Oxidation Reactions Using Molecular Oxygen

    Beier, Matthias Josef

    Heterogeneously catalyzed selective oxidation reactions have attracted a lot of attention in recent time. The first part of the present thesis provides an overview over heterogeneous copper and silver catalysts for selective oxidations in the liquid phase and compared the performance and catalytic...... that both copper and silver can function as complementary catalyst materials to gold showing different catalytic properties and being more suitable for hydrocarbon oxidation reactions. Potential opportunities for future research were outlined. In an experimental study, the potential of silver as a catalyst...... revealed that all catalysts were more active in combination with ceria nanoparticles and that under the tested reaction conditions silver was equally or even more efficient than the gold catalysts. Calcination at 900 °C of silver on silica prepared by impregnation afforded a catalyst which was used...

  11. Myoglobin-Catalyzed Olefination of Aldehydes.

    Tyagi, Vikas; Fasan, Rudi

    2016-02-12

    The olefination of aldehydes constitutes a most valuable and widely adopted strategy for constructing carbon-carbon double bonds in organic chemistry. While various synthetic methods have been made available for this purpose, no biocatalysts are known to mediate this transformation. Reported herein is that engineered myoglobin variants can catalyze the olefination of aldehydes in the presence of α-diazoesters with high catalytic efficiency (up to 4,900 turnovers) and excellent E diastereoselectivity (92-99.9 % de). This transformation could be applied to the olefination of a variety of substituted benzaldehydes and heteroaromatic aldehydes, also in combination with different alkyl α-diazoacetate reagents. This work provides a first example of biocatalytic aldehyde olefination and extends the spectrum of synthetically valuable chemical transformations accessible using metalloprotein-based catalysts. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia.

    Adriana Cristofano

    Full Text Available This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer's disease. Twenty-nine patients with probable Alzheimer's disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L to subjective memory complaint (4.3±0.9 μmol/L, mild cognitive impairment (4.0±0.53 μmol/L, up to Alzheimer's disease (3.5±0.6 μmol/L group (p<0.001. The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer's disease group; and subjective memory complaint vs. Alzheimer's disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer's disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer's disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer's disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal

  13. Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia

    Sapere, Nadia; La Marca, Giancarlo; Angiolillo, Antonella; Vitale, Michela; Corbi, Graziamaria; Scapagnini, Giovanni; Intrieri, Mariano; Russo, Claudio

    2016-01-01

    This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer’s disease. Twenty-nine patients with probable Alzheimer’s disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L) to subjective memory complaint (4.3±0.9 μmol/L), mild cognitive impairment (4.0±0.53 μmol/L), up to Alzheimer’s disease (3.5±0.6 μmol/L) group (p<0.001). The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer’s disease group; and subjective memory complaint vs. Alzheimer’s disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer’s disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer’s disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer’s disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal

  14. Disruption of the Acyl-CoA binding protein gene delays hepatic adaptation to metabolic changes at weaning

    Neess, Ditte; Marcher, Ann-Britt; Bloksgaard, Maria

    The acyl-CoA binding protein/diazepam binding inhibitor (ACBP/DBI) is an evolutionary conserved intracellular protein that binds C14-C22 acyl-CoA esters with very high affinity. ACBP is thought to act as an acyl-CoA transporter, and in vitro analyses have indicated that ACBP can transport acyl......-CoA esters between different enzymatic systems. However, little is known about the in vivo function in mammalian cells. We have generated mice with targeted disruption of ACBP (ACBP-/-). These mice are viable and fertile and develop normally. However, around weaning the ACBP-/- mice show decreased growth......) family, around the weaning period. As a result, the hepatic de novo cholesterogenesis is significantly decreased at weaning. The delayed induction of SREBP target genes around weaning is caused by a compromised processing and decreased expression of SREBP precursors leading to reduced binding of SREBP...

  15. Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver

    Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang [Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 China (China); Chonan, Ritsu [Koei Kogyo Co., Ltd., Tokyo, 101-0063 Japan (Japan); Yamahara, Johji [Pharmafood Institute, Kyoto, 602-8136 Japan (Japan); Wang, Jianwei, E-mail: wangjianwei1968@gmail.com [Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016 China (China); Li, Yuhao, E-mail: yuhao@sitcm.edu.au [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, NSW 2000 Australia (Australia)

    2014-10-15

    Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. - Highlights: • We investigated the anti-steatotic effect of mangiferin (MA) in fructose-fed SHR. • MA (15 mg/kg/day for 7 weeks) ameliorated fructose-induced fatty liver in

  16. Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver

    Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang; Chonan, Ritsu; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2014-01-01

    Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. - Highlights: • We investigated the anti-steatotic effect of mangiferin (MA) in fructose-fed SHR. • MA (15 mg/kg/day for 7 weeks) ameliorated fructose-induced fatty liver in

  17. Highly selective probe based on imine linkage for Zn{sup 2+} and HSO{sub 3}{sup −} in mixed aqueous media

    Kaur, Kamaljot; Chaudhary, Savita; Singh, Sukhjinder; Mehta, S.K., E-mail: skmehta@pu.ac.in

    2015-04-15

    A simple salicylaldehyde derived Schiff base N, N′- bis (p-chloro salicylidene)-1, 2- ethylenediamine (L) was synthesized and characterized. The receptor demonstrates simultaneous dual channel chromogenic and fluorogenic signaling towards HSO{sub 3}{sup −} and Zn{sup 2+} in mixed aqueous media. Solvatochromism was employed systematically for modulating its optoelectronic properties. The probe was successfully assessed to monitor HSO{sub 3}{sup −} detection via UV–vis spectroscopy. DFT calculations and {sup 1}H NMR spectroscopy further support the results based on shifting of equilibrium. Moreover, the sensor showed large fluorescence enhancement with blue-shift of 48 nm after addition of Zn{sup 2+}. The probe exhibits high selectivity over other competitive ions with high detection limit of 6.54×10{sup −5} M and 3.21×10{sup −6} M for HSO{sub 3}{sup −} and Zn{sup 2+}, respectively. Importantly, this is one of the rare reports in which Schiff base was utilized for the fabrication of chromogenic or fluorogenic sensor using solvent effect for multianalyte detection. - Highlights: • Easy synthesis of highly selective and sensitive Salicylideneaniline moiety. • Solvatochromism induced tautomerism between the enol-imine and keto-amine forms. • Computational studies revealing the effect of solvent on stability of NH form. • Discriminative detection of HSO{sub 3}{sup −} and Zn{sup 2+} by different spectroscopic techniques. • Optical feedbacks as absorption transitions with HSO{sub 3}{sup −} on bisulphite adduct formation. • Fluorescence enhancement for Zn{sup 2+} based on imine binding mechanism.

  18. Acylated ghrelin concentrations are markedly decreased during pregnancy in mothers with and without gestational diabetes: relationship with cholinesterase.

    Tham, Elaine; Liu, Jianhua; Innis, Sheila; Thompson, David; Gaylinn, Bruce D; Bogarin, Roberto; Haim, Alon; Thorner, Michael O; Chanoine, Jean-Pierre

    2009-05-01

    Acylated (octanoylated) ghrelin stimulates food intake and growth hormone secretion and is deacylated into desacyl ghrelin by butyrylcholinesterase. Acylated and desacyl ghrelin both promote adipogenesis. Ghrelin concentrations decrease with hyperglycemia and hyperinsulinism. We hypothesized that 1) acylated ghrelin increases during pregnancy, contributing positively to energy balance, but is lower in women with gestational diabetes and 2) butyrylcholinesterase activity is inversely correlated with acylated ghrelin concentrations. In a first group of subjects, using two-site sandwich ghrelin assays that specifically detect full-length forms, we investigated women with and without gestational diabetes (n = 14/group) during pregnancy and after delivery. We examined whether changes in ghrelin during a test meal were correlated with changes in pituitary growth hormone [assessed through calculation of the area under the curve (AUC) during the test meal]. In postpartum subjects, the percent of total ghrelin that is acylated was four to five times higher than previously observed using single antibody assays. During pregnancy, acylated ghrelin concentrations (mean +/- SE) were lower compared with the postpartum period throughout the meal (AUC 1.2 +/- 0.2 vs. 10.2 +/- 1.9 ng.ml(-1).90 min(-1), P < 0.001). In the postpartum, acylated ghrelin and growth hormone were positively correlated (r = 0.50, P = 0.007). Desacyl (but not acylated) ghrelin was increased in subjects with gestational diabetes during and after pregnancy (AUC 15.4 +/- 1.9 vs. 8.6 +/- 1.2 ng.ml(-1).90 min(-1), P = 0.005). In a second group of subjects (n = 13), acylated ghrelin was similarly suppressed during pregnancy. Circulating octanoate concentrations (3.1 +/- 0.5 vs. 4.5 +/- 0.6 microg/ml, P = 0.029) and cholinesterase activity (705 +/- 33 vs. 1,013 +/- 56 U/ml, P < 0.001) were lower during pregnancy compared with the postpartum period. In conclusion, acylated ghrelin markedly decreases during pregnancy

  19. Synthesis and biological evaluation of S-acyl-3-thiopropyl prodrugs of N-phosphonoacetyl-L-aspartate (PALA).

    Gagnard, Valérie; Leydet, Alain; Le Mellay, Véronique; Aubenque, Marielle; Morère, Alain; Montero, Jean-Louis

    2003-10-01

    The synthesis of new prodrugs of PALA characterised by the presence of S-acyl-3-thiopropyl, as enzyme-labile groups on the phosphonate moiety of PALA, is reported. The cytotoxic activities of PALA prodrugs were determined against human cell line (SW1573 lung carcinoma cells). A number of prodrugs bearing S-pivaloyl as acyl groups displayed cytotoxic activity in the same order of magnitude of PALA.

  20. Ethylene glycol causes acyl chain disordering in liquid-crystalline, unsaturated phospholipid model membranes, as measured by 2H NMR

    Nicolay, K.; Kruijff, B. de; Smaal, E.B.

    1986-01-01

    2 H NMR has been used to probe the effects of ethylene glycol at the level of the acyl chains in liposomes prepared from dioleoylphosphatidic acid or dioleoylphosphatidylcholine, labeled with 2 H at the 11-position of both oleic acid chains. Increasing concentrations of ethylene glycol lead to a proportional and substantial decrease in the quadrupolar splittings, measured from the 2 H NMR spectra of both liposomal system, indicative of acyl chain disordering. (Auth.)

  1. In vitro reconstitution of sortase-catalyzed pilus polymerization reveals structural elements involved in pilin cross-linking.

    Chang, Chungyu; Amer, Brendan R; Osipiuk, Jerzy; McConnell, Scott A; Huang, I-Hsiu; Hsieh, Van; Fu, Janine; Nguyen, Hong H; Muroski, John; Flores, Erika; Ogorzalek Loo, Rachel R; Loo, Joseph A; Putkey, John A; Joachimiak, Andrzej; Das, Asis; Clubb, Robert T; Ton-That, Hung

    2018-06-12

    Covalently cross-linked pilus polymers displayed on the cell surface of Gram-positive bacteria are assembled by class C sortase enzymes. These pilus-specific transpeptidases located on the bacterial membrane catalyze a two-step protein ligation reaction, first cleaving the LPXTG motif of one pilin protomer to form an acyl-enzyme intermediate and then joining the terminal Thr to the nucleophilic Lys residue residing within the pilin motif of another pilin protomer. To date, the determinants of class C enzymes that uniquely enable them to construct pili remain unknown. Here, informed by high-resolution crystal structures of corynebacterial pilus-specific sortase (SrtA) and utilizing a structural variant of the enzyme (SrtA 2M ), whose catalytic pocket has been unmasked by activating mutations, we successfully reconstituted in vitro polymerization of the cognate major pilin (SpaA). Mass spectrometry, electron microscopy, and biochemical experiments authenticated that SrtA 2M synthesizes pilus fibers with correct Lys-Thr isopeptide bonds linking individual pilins via a thioacyl intermediate. Structural modeling of the SpaA-SrtA-SpaA polymerization intermediate depicts SrtA 2M sandwiched between the N- and C-terminal domains of SpaA harboring the reactive pilin and LPXTG motifs, respectively. Remarkably, the model uncovered a conserved TP(Y/L)XIN(S/T)H signature sequence following the catalytic Cys, in which the alanine substitutions abrogated cross-linking activity but not cleavage of LPXTG. These insights and our evidence that SrtA 2M can terminate pilus polymerization by joining the terminal pilin SpaB to SpaA and catalyze ligation of isolated SpaA domains in vitro provide a facile and versatile platform for protein engineering and bio-conjugation that has major implications for biotechnology.

  2. Transcriptome analysis of acyl-homoserine lactone-based quorum sensing regulation in Yersinia pestis [corrected].

    Christopher N LaRock

    Full Text Available The etiologic agent of bubonic plague, Yersinia pestis, senses self-produced, secreted chemical signals in a process named quorum sensing. Though the closely related enteric pathogen Y. pseudotuberculosis uses quorum sensing system to regulate motility, the role of quorum sensing in Y. pestis has been unclear. In this study we performed transcriptional profiling experiments to identify Y. pestis quorum sensing regulated functions. Our analysis revealed that acyl-homoserine lactone-based quorum sensing controls the expression of several metabolic functions. Maltose fermentation and the glyoxylate bypass are induced by acyl-homoserine lactone signaling. This effect was observed at 30°C, indicating a potential role for quorum sensing regulation of metabolism at temperatures below the normal mammalian temperature. It is proposed that utilization of alternative carbon sources may enhance growth and/or survival during prolonged periods in natural habitats with limited nutrient sources, contributing to maintenance of plague in nature.

  3. Regulation of lipolytic activity by long-chain acyl-coenzyme A in islets and adipocytes

    Hu, Liping; Deeney, Jude T; Nolan, Christopher J

    2005-01-01

    -cells. The mechanisms by which lipolysis is regulated in different tissues is, therefore, of considerable interest. Here, the effects of long-chain acyl-CoA esters (LC-CoA) on lipase activity in islets and adipocytes were compared. Palmitoyl-CoA (Pal-CoA, 1-10 microM) stimulated lipase activity in islets from both....... The inhibitory effect of LC-CoA on adipocyte HSL was dependent on phosphorylation and enhanced by acyl-CoA-binding protein (ACBP). In contrast, the stimulatory effect on islet lipase activity was blocked by ACBP, presumably due to binding and sequestration of LC-CoA. These data suggest the following intertissue...

  4. Global and Phylogenetic Distribution of Quorum Sensing Signals, Acyl Homoserine Lactones, in the Family of Vibrionaceae

    Rasmussen, Bastian Barker; Nielsen, Kristian Fog; Machado, Henrique

    2014-01-01

    Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae in the en......Bacterial quorum sensing (QS) and the corresponding signals, acyl homoserine lactones (AHLs), were first described for a luminescent Vibrio species. Since then, detailed knowledge has been gained on the functional level of QS; however, the abundance of AHLs in the family of Vibrionaceae...... violaceum reporter strains. Ethyl acetate extracts of the cultures were analysed by ultra-high performance liquid chromatography-high resolution mass spectrometry (MS) with automated tandem MS confirmation for AHLs. N-(3-hydroxy-hexanoyl) (OH-C6) and N-(3-hydroxy-decanoyl) (OH-C10) homoserine lactones were...

  5. Biocatalytic acylation of carbohydrates with fatty acids from palm fatty acid distillates.

    Chaiyaso, Thanongsak; H-Kittikun, Aran; Zimmermann, Wolfgang

    2006-05-01

    Palm fatty acid distillates (PFAD) are by-products of the palm oil refining process. Their use as the source of fatty acids, mainly palmitate, for the biocatalytic synthesis of carbohydrate fatty acid esters was investigated. Esters could be prepared in high yields from unmodified acyl donors and non-activated free fatty acids obtained from PFAD with an immobilized Candida antarctica lipase preparation. Acetone was found as a compatible non-toxic solvent, which gave the highest conversion yields in a heterogeneous reaction system without the complete solubilization of the sugars. Glucose, fructose, and other acyl acceptors could be employed for an ester synthesis with PFAD. The synthesis of glucose palmitate was optimized with regard to the water activity of the reaction mixture, the reaction temperature, and the enzyme concentration. The ester was obtained with 76% yield from glucose and PFAD after reaction for 74 h with 150 U ml(-1) immobilized lipase at 40 degrees C in acetone.

  6. Recombinant expression, purification, and characterization of an acyl-CoA binding protein from Aspergillus oryzae.

    Hao, Qing; Liu, Xiaoguang; Zhao, Guozhong; Jiang, Lu; Li, Ming; Zeng, Bin

    2016-03-01

    To characterize biochemically the lipid metabolism-regulating acyl-CoA binding protein (ACBP) from the industrially-important fungus Aspergillus oryzae. A full-length cDNA encoding a candidate ACBP from A. oryzae (AoACBP) was cloned and expressed in Escherichia coli as a maltose-binding protein (MBP) fusion protein. The MBP-AoACBP protein was purified by an amylose resin chromatography column. SDS-PAGE showed that MBP-AoACBP has an estimated molecular weight of 82 kDa. Microscale thermophoresis binding assay showed that the recombinant AoACBP displayed much greater affinity for palmitoyl-CoA (K d = 80 nM) than for myristoyl-CoA (K d = 510 nM), thus demonstrating the preference of AoACBP for long-chain acyl-CoA. The data support the identification of AoACBP as a long-chain ACBP in A. oryzae.

  7. Age dependent accumulation of N-acyl-ethanolamine phospholipids in ischemic rat brain

    Moesgaard, B.; Petersen, G.; Hansen, Harald S.

    2000-01-01

    N-acyl-ethanolamine phospholipids (NAPE) can be formed as a stress response during neuronal injury, and they are precursors for N-acyl- ethanolamines (NAE), some of which are endocannabinoids. The levels of NAPE accumulated during post-decapitative ischemia (6 h at 37°C) were studied in rat brains...... of various age (1, 6, 12, 19, 30, and ~70 days) by the use of P NMR spectroscopy of lipid extracts. This ability to accumulate NAPE was compared with the activity of N-acyltransferase and of NAPE-hydrolyzing phospholipase D (NAPE-PLD) in brain microsomes. These two enzymes are involved in the formation...... brains NAPE accumulation could not be detected (detection limit 0.09 %)]; and 2) this age pattern of accumulation can be explained by a combination of the decreased activity of N- acyltransferase and the increased activity of NAPE-PLD during development. These results point out that it would...

  8. Novel endogenous N-acyl amides activate TRPV1-4 receptors, BV-2 microglia, and are regulated in brain in an acute model of inflammation

    Raboune, Siham; Stuart, Jordyn M.; Leishman, Emma; Takacs, Sara M.; Rhodes, Brandon; Basnet, Arjun; Jameyfield, Evan; McHugh, Douglas; Widlanski, Theodore; Bradshaw, Heather B.

    2014-01-01

    A family of endogenous lipids, structurally analogous to the endogenous cannabinoid, N-arachidonoyl ethanolamine (Anandamide), and called N-acyl amides have emerged as a family of biologically active compounds at TRP receptors. N-acyl amides are constructed from an acyl group and an amine via an amide bond. This same structure can be modified by changing either the fatty acid or the amide to form potentially hundreds of lipids. More than 70 N-acyl amides have been identified in nature. We have ongoing studies aimed at isolating and characterizing additional members of the family of N-acyl amides in both central and peripheral tissues in mammalian systems. Here, using a unique in-house library of over 70 N-acyl amides we tested the following three hypotheses: (1) Additional N-acyl amides will have activity at TRPV1-4, (2) Acute peripheral injury will drive changes in CNS levels of N-acyl amides, and (3) N-acyl amides will regulate calcium in CNS-derived microglia. Through these studies, we have identified 20 novel N-acyl amides that collectively activate (stimulating or inhibiting) TRPV1-4. Using lipid extraction and HPLC coupled to tandem mass spectrometry we showed that levels of at least 10 of these N-acyl amides that activate TRPVs are regulated in brain after intraplantar carrageenan injection. We then screened the BV2 microglial cell line for activity with this N-acyl amide library and found overlap with TRPV receptor activity as well as additional activators of calcium mobilization from these lipids. Together these data provide new insight into the family of N-acyl amides and their roles as signaling molecules at ion channels, in microglia, and in the brain in the context of inflammation. PMID:25136293

  9. Isotope effects in the non enzymic glucation of hemoglobin catalyzed by phosphate

    Gil, H.; Mata-Segreda, J.; Schowen, R.

    1991-01-01

    The reaction of hemoglobin, mainly at the N-terminal valine, with glucose exhibits identical rates in protium and deuterium oxides, both for the buffer-independent rate and for the first-order rate in phosphate buffer. Under the conditions employed, imine formation is relatively rapid and events in the course of the Amadori rearrangement must limit the rate. A very-slow, phosphate-induced reorganization of hemoglobin-glucose imine may be the most likely candidate for the rate-limiting step. (author)

  10. Density functional theory studies on the nano-scaled composites consisted of graphene and acyl hydrazone molecules

    Ren, J. L.; Zhou, L.; Lv, Z. C.; Ding, C. H.; Wu, Y. H.; Bai, H. C.

    2016-07-01

    Graphene, which is the first obtained single atomic layer 2D materials, has drawn a great of concern in nano biotechnology due to the unique property. On one hand, acyl hydrazone compounds belonging to the Schif bases have aroused considerable attention in medicine, pharmacy, and analytical reagent. However, few understanding about the interaction between graphene and acyl hydrazone molecules is now available. And such investigations are much crucial for the applications of these new nano-scaled composites. The current work revealed theoretical investigations on the nano-scaled composites built by acyl hydrazone molecules loaded on the surface of graphene. The relative energy, electronic property and the interaction between the counterparts of graphene/acyl hydrazone composites are investigated based on the density functional theory calculations. According to the obtained adsorption energy, the formation of the nano-scaled composite from the isolated graphene and acyl hydrazone molecule is exothermic, and thus it is energetically favorable to form these nano composites in viewpoint of total energy change. The frontier molecular orbital for the nano composite is mainly distributed at the graphene part, leading to that the energy levels of the frontier molecular orbital of the nano composites are very close to that of isolated graphene. Moreover, the counterpart interaction for the graphene/acyl hydrazone composites is also explored based on the discussions of orbital hybridization, charge redistribution and Van der Waals interaction.

  11. Des-acyl ghrelin prevents heatstroke-like symptoms in rats exposed to high temperature and high humidity.

    Inoue, Yoshiyuki; Hayashi, Yujiro; Kangawa, Kenji; Suzuki, Yoshihiro; Murakami, Noboru; Nakahara, Keiko

    2016-02-26

    We have shown previously that des-acyl ghrelin decreases body temperature in rats through activation of the parasympathetic nervous system. Here we investigated whether des-acyl ghrelin ameliorates heatstroke in rats exposed to high temperature. Peripheral administration of des-acyl ghrelin significantly attenuated hyperthermia induced by exposure to high-temperature (35°C) together with high humidity (70-80%). Although biochemical analysis revealed that exposure to high temperature significantly increased hematocrit and the serum levels of aspartate amino transferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), creatinine and electrolytes (Na(+), K(+), Cl(-)), most of these heatstroke-associated reactions were significantly reduced by treatment with des-acyl ghrelin. The level of des-acyl ghrelin in plasma was also found to be significantly increased under high-temperature conditions. These results suggest that des-acyl ghrelin could be useful for preventing heatstroke under high temperature condition. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Cholesterol esterification by mouse liver homogenate. Contribution to the study of ACYL-CoA: Cholesterol ACYL transferase in mammalian liver

    Soares, M.G.C.B.

    1976-01-01

    A cholesterol- esterifying enzyme from mouse liver has been partially characterized. The enzyme which showed optimum activity at pH 7,1 and required ATP and CoA, was identified as an acyl CoA: cholesterol acyl transferase (E.C.2.3.1.26). As a fuction of time the percentage of esterified cholesterol increased linearly during the first hour of incubation and continued to increase but not linearly with 4 hours, after which time no further net esterefication was observed. The relative concentration of esterified cholesterol remained constant between the fourth and twelveth hours of incubation but afterwards decreased when the incubation continued until 24 hours. The cholesterol- esterifying activity was 24,0+- 2,9 nmoles cholesterol esterified per gram tissue wet weight per minute. The mean percentages of free cholesterol esterified in and 24 hours respectively were 14,8+- 1,6 e 21,9+- 4,5. The subfractionation of labelled cholesteryl esters after one hour incubation of liver homogenate with 4-C 14 -Cholesterol showed the order of preference for the formation of the different ester classes to be monounsatured > diunsatured ≥ saturated >> polyunsaturated. The properties of the enzyme frommouse liver do not markedly differ from those of the previously recorded ACAT activity of rat liver. (Author) [pt

  13. Acquired multiple Acyl-CoA dehydrogenase deficiency in 10 horses with atypical myopathy.

    Westermann, C M; Dorland, L; Votion, D M; de Sain-van der Velden, M G M; Wijnberg, I D; Wanders, R J A; Spliet, W G M; Testerink, N; Berger, R; Ruiter, J P N; van der Kolk, J H

    2008-05-01

    The aim of the current study was to assess lipid metabolism in horses with atypical myopathy. Urine samples from 10 cases were subjected to analysis of organic acids, glycine conjugates, and acylcarnitines revealing increased mean excretion of lactic acid, ethylmalonic acid, 2-methylsuccinic acid, butyrylglycine, (iso)valerylglycine, hexanoylglycine, free carnitine, C2-, C3-, C4-, C5-, C6-, C8-, C8:1-, C10:1-, and C10:2-carnitine as compared with 15 control horses (12 healthy and three with acute myopathy due to other causes). Analysis of plasma revealed similar results for these predominantly short-chain acylcarnitines. Furthermore, measurement of dehydrogenase activities in lateral vastus muscle from one horse with atypical myopathy indeed showed deficiencies of short-chain acyl-CoA dehydrogenase (0.66 as compared with 2.27 and 2.48 in two controls), medium-chain acyl-CoA dehydrogenase (0.36 as compared with 4.31 and 4.82 in two controls) and isovaleryl-CoA dehydrogenase (0.74 as compared with 1.43 and 1.61 nmol min(-1) mg(-1) in two controls). A deficiency of several mitochondrial dehydrogenases that utilize flavin adenine dinucleotide as cofactor including the acyl-CoA dehydrogenases of fatty acid beta-oxidation, and enzymes that degrade the CoA-esters of glutaric acid, isovaleric acid, 2-methylbutyric acid, isobutyric acid, and sarcosine was suspected in 10 out of 10 cases as the possible etiology for a highly fatal and prevalent toxic equine muscle disease similar to the combined metabolic derangements seen in human multiple acyl-CoA dehydrogenase deficiency also known as glutaric acidemia type II.

  14. Ultraviolet stimulated melanogenesis by human melanocytes is augmented by di-acyl glycerol but not TPA

    Friedmann, P.S.; Wren, F.E.; Matthews, J.N.

    1990-01-01

    Epidermal melanocytes (MC) synthesize melanin in response to ultraviolet radiation (UVR). The mechanisms mediating the UV-induced activation of melanogenesis are unknown but since UVR induces turnover of membrane phospholipids generating prostaglandins (PGs) and other products, it is possible that one of these might provide the activating signal. We have examined the effects of prostaglandins (PGs) E1, E2, D2, F2 alpha, and di-acyl glycerol upon the UV-induced responses of cultured human MC and the Cloudman S91 melanoma cell line. The PGs had little effect on unirradiated cells and did not alter the response to UVR in either human MC or S91 melanoma cells. However, a synthetic analogue of di-acyl glycerol, 1-oleyl 2-acetyl glycerol (OAG), caused a significant (P less than 0.0001), dose-related augmentation of melanin content both in human MC (seven-fold) and S91 cells (three-fold). UVR caused a significant augmentation of the OAG-induced melanogenesis of both human MC and S91 cells. Since OAG is known to activate protein kinase C, it was possible that the observed modulation of the UVR signal could be via that pathway. Di-octanoyl glycerol, another di-acyl glycerol, which activates kinase C, caused a small (70%) increase in melanogenesis in MC which was not altered by UVR. However, 12-0 tetradecanoyl phorbol 13-acetate (TPA), a potent activator of protein kinase C, had no significant effect on either basal or UV-induced melanin synthesis in either cell type. These data suggest that the UV-induced signal activating melanogenesis could be mediated by di-acyl glycerol. Furthermore, they imply that the signal is transduced via an alternative, pathway that might be independent of protein kinase C

  15. Two new acylated flavonol glycosides from Mimosa pigra L. leaves sub-family Mimosoideae

    Chinedu J. Okonkwo

    2016-12-01

    Conclusion: Myricetin, quercetin and their glycoside derivatives are strong antioxidants; and elicit cytotoxic effect on human cancer cell lines among other pharmacological activities. The isolation of acylated flavonoids in M. pigra provided an important insight on the evolutionary trend of the medicinal plant. While the dominance of flavonols, may account for the various ethnomedicinal uses of the herb and the mechanism and mode of its confirmed pharmacological actions.

  16. Acyl chloride carbon insertion into dicarbaborane cages - new route to tricarbollide cages

    Štíbr, Bohumil

    2015-01-01

    Roč. 87, č. 2 (2015), s. 135-142 ISSN 0033-4545. [IMEBORON/15./. Praha, 24.08.2014-28.08.2014] R&D Projects: GA ČR(CZ) GAP207/11/0705 Institutional support: RVO:61388980 Keywords : acyl chlorides * carbon insertion * carboranes * IMEBORON-XV * metallatricarbollides * tricarbollides Subject RIV: CA - Inorganic Chemistry Impact factor: 2.615, year: 2015

  17. Accumulation of medium-chain, saturated fatty acyl moieties in seed oils of transgenic Camelina sativa.

    Zhaohui Hu

    Full Text Available With its high seed oil content, the mustard family plant Camelina sativa has gained attention as a potential biofuel source. As a bioenergy crop, camelina has many advantages. It grows on marginal land with low demand for water and fertilizer, has a relatively short life cycle, and is stress tolerant. As most other crop seed oils, camelina seed triacylglycerols (TAGs consist of mostly long, unsaturated fatty acyl moieties, which is not desirable for biofuel processing. In our efforts to produce shorter, saturated chain fatty acyl moieties in camelina seed oil for conversion to jet fuel, a 12:0-acyl-carrier thioesterase gene, UcFATB1, from California bay (Umbellularia californica Nutt. was expressed in camelina seeds. Up to 40% of short chain laurate (C12:0 and myristate (C14:0 were present in TAGs of the seed oil of the transgenics. The total oil content and germination rate of the transgenic seeds were not affected. Analysis of positions of these two fatty acyl moieties in TAGs indicated that they were present at the sn-1 and sn-3 positions, but not sn-2, on the TAGs. Suppression of the camelina KASII genes by RNAi constructs led to higher accumulation of palmitate (C16:0, from 7.5% up to 28.5%, and further reduction of longer, unsaturated fatty acids in seed TAGs. Co-transformation of camelina with both constructs resulted in enhanced accumulation of all three medium-chain, saturated fatty acids in camelina seed oils. Our results show that a California bay gene can be successfully used to modify the oil composition in camelina seed and present a new biological alternative for jet fuel production.

  18. A Scalable Method for Regioselective 3-Acylation of 2-Substituted Indoles under Basic Conditions

    Johansson, Karl Henrik; Urruticoechea, Andoni; Larsen, Inna

    2015-01-01

    Privileged structures such as 2-arylindoles are recurrent molecular scaffolds in bioactive molecules. We here present an operationally simple, high yielding and scalable method for regioselective 3-acylation of 2-substituted indoles under basic conditions using functionalized acid chlorides. The ....... The method shows good tolerance to both electron-withdrawing and donating substituents on the indole scaffold and gives ready access to a variety of functionalized 3-acylindole building blocks suited for further derivatization....

  19. Iodine-catalyzed diazo activation to access radical reactivity.

    Li, Pan; Zhao, Jingjing; Shi, Lijun; Wang, Jin; Shi, Xiaodong; Li, Fuwei

    2018-05-17

    Transition-metal-catalyzed diazo activation is a classical way to generate metal carbene, which are valuable intermediates in synthetic organic chemistry. An alternative iodine-catalyzed diazo activation is disclosed herein under either photo-initiated or thermal-initiated conditions, which represents an approach to enable carbene radical reactivity. This metal-free diazo activation strategy were successfully applied into olefin cyclopropanation and epoxidation, and applying this method to pyrrole synthesis under thermal-initiated conditions further demonstrates the unique reactivity using this method over typical metal-catalyzed conditions.

  20. A Novel 3-Sulfinopropionyl Coenzyme A (3SP-CoA) Desulfinase from Advenella mimigardefordensis Strain DPN7T Acting as a Key Enzyme during Catabolism of 3,3′-Dithiodipropionic Acid Is a Member of the Acyl-CoA Dehydrogenase Superfamily

    Schürmann, Marc; Deters, Anika; Wübbeler, Jan Hendrik

    2013-01-01

    3-Sulfinopropionyl coenzyme A (3SP-CoA) desulfinase (AcdDPN7) is a new desulfinase that catalyzes the sulfur abstraction from 3SP-CoA in the betaproteobacterium Advenella mimigardefordensis strain DPN7T. During investigation of a Tn5::mob-induced mutant defective in growth on 3,3′-dithiodipropionate (DTDP) and also 3-sulfinopropionate (3SP), the transposon insertion was mapped to an open reading frame with the highest homology to an acyl-CoA dehydrogenase (Acd) from Burkholderia phenoliruptrix strain BR3459a (83% identical and 91% similar amino acids). An A. mimigardefordensis Δacd mutant was generated and verified the observed phenotype of the Tn5::mob-induced mutant. For enzymatic studies, AcdDPN7 was heterologously expressed in Escherichia coli BL21(DE3)/pLysS by using pET23a::acdDPN7. The purified protein is yellow and contains a noncovalently bound flavin adenine dinucleotide (FAD) cofactor, as verified by high-performance liquid chromatography–electrospray ionization mass spectrometry (HPLC-ESI-MS) analyses. Size-exclusion chromatography revealed a native molecular mass of about 173 kDa, indicating a homotetrameric structure (theoretically 179 kDa), which is in accordance with other members of the acyl-CoA dehydrogenase superfamily. In vitro assays unequivocally demonstrated that the purified enzyme converted 3SP-CoA into propionyl-CoA and sulfite (SO32−). Kinetic studies of AcdDPN7 revealed a Vmax of 4.19 μmol min−1 mg−1, an apparent Km of 0.013 mM, and a kcat/Km of 240.8 s−1 mM−1 for 3SP-CoA. However, AcdDPN7 is unable to perform a dehydrogenation, which is the usual reaction catalyzed by members of the acyl-CoA dehydrogenase superfamily. Comparison to other known desulfinases showed a comparably high catalytic efficiency of AcdDPN7 and indicated a novel reaction mechanism. Hence, AcdDPN7 encodes a new desulfinase based on an acyl-CoA dehydrogenase (EC 1.3.8.x) scaffold. Concomitantly, we identified the gene product that is responsible for

  1. New anthrarobin acyl derivatives as butyrylcholinesterase inhibitors: synthesis, in vitro and in silico studies

    Mehreen Lateef

    2017-07-01

    Full Text Available To treat Alzheimer's disease (AD, the available candidates are effective only against mild AD or have side effects. So, a study was planned to synthesis new candidates that may have good potential to treat AD. A series of new anthrarobin acyl derivatives (2–8 were synthesized by the reaction of anthrarobin (1 and acetic anhydride/acyl chlorides. The product were characterized by 1H NMR and EI-MS, and evaluated for butyrylcholinesterase (BuChE inhibition activity. Compounds 5 and 4 showed notable BuChE inhibitory potential with IC50 5.3 ± 1.23 and 17.2 ± 0.47 μM, respectively when compared with the standard eserine (IC50 7.8 ± 0.27 μM, compound 5 showed potent BuChE inhibition potential than the standard eserine. The active compounds 5 and 4 have acyl groups at 2-OH and 10-OH positions which may be responsible for inhibitory potential as this orientation is absent in other products. In silico studies of 5 and 4 products revealed the high inhibitory potential due to stable binding of ligand with the BuChE active sites with docking energy score −18.8779 kcal/mol and −23.1159 kcal/mol, respectively. Subsequently, compound 5 that have potent BuChE inhibitory activity could be the potential candidate for drug development for Alzheimer’s disease.

  2. Endophytic Actinomycetes: A Novel Source of Potential Acyl Homoserine Lactone Degrading Enzymes

    Surang Chankhamhaengdecha

    2013-01-01

    Full Text Available Several Gram-negative pathogenic bacteria employ N-acyl-L-homoserine lactone (HSL quorum sensing (QS system to control their virulence traits. Degradation of acyl-HSL signal molecules by quorum quenching enzyme (QQE results in a loss of pathogenicity in QS-dependent organisms. The QQE activity of actinomycetes in rhizospheric soil and inside plant tissue was explored in order to obtain novel strains with high HSL-degrading activity. Among 344 rhizospheric and 132 endophytic isolates, 127 (36.9% and 68 (51.5% of them, respectively, possessed the QQE activity. The highest HSL-degrading activity was at 151.30±3.1 nmole/h/mL from an endophytic actinomycetes isolate, LPC029. The isolate was identified as Streptomyces based on 16S  rRNA gene sequence similarity. The QQE from LPC029 revealed HSL-acylase activity that was able to cleave an amide bond of acyl-side chain in HSL substrate as determined by HPLC. LPC029 HSL-acylase showed broad substrate specificity from C6- to C12-HSL in which C10HSL is the most favorable substrate for this enzyme. In an in vitro pathogenicity assay, the partially purified HSL-acylase efficiently suppressed soft rot of potato caused by Pectobacterium carotovorum ssp. carotovorum as demonstrated. To our knowledge, this is the first report of HSL-acylase activity derived from an endophytic Streptomyces.

  3. Processing and fatty acid acylation of RAS1 and RAS2 proteins in Saccharomyces cerevisiae

    Fujiyama, A.; Tamanoi, F.

    1986-01-01

    The authors demonstrate the pathway for the biosynthesis of RAS1 and RAS2 gene products of Saccharomyces cerevisiae leading to their localization in membranes. The primary translation products of these genes are detected in a soluble fraction. Shortly after synthesis, these precursor molecules are converted to forms that migrate slightly faster than the precursor forms on a NaDodSO 4 /polyacrylamide gel. These processed proteins are further modified by fatty acid acylation, which is detected by [ 3 H]palmitic acid labeling. The acylated derivatives are found exclusively in cell membranes, indicating the translocation of the RAS proteins from cytosol to membranes during maturation process. The attached fatty acids can be released by mild alkaline hydrolysis, suggesting that the linkage between the fatty acid and the protein is an ester bond. The site of the modification by fatty acid is presumably localized to the COOH-terminal portion of the RAS proteins. Fraction of the membranes by sucrose gradient demonstrates that a majority of the fatty-acylated RAS proteins are localized in plasma membrane

  4. Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-nitrogen cleavage: general strategy for amide N-C bond activation.

    Meng, Guangrong; Szostak, Michal

    2016-06-15

    The first palladium-catalyzed Suzuki-Miyaura cross-coupling of amides with boronic acids for the synthesis of ketones by sterically-controlled N-C bond activation is reported. The transformation is characterized by operational simplicity using bench-stable, commercial reagents and catalysts, and a broad substrate scope, including substrates with electron-donating and withdrawing groups on both coupling partners, steric-hindrance, heterocycles, halides, esters and ketones. The scope and limitations are presented in the synthesis of >60 functionalized ketones. Mechanistic studies provide insight into the catalytic cycle of the cross-coupling, including the first experimental evidence for Pd insertion into the amide N-C bond. The synthetic utility is showcased by a gram-scale cross-coupling and cross-coupling at room temperature. Most importantly, this process provides a blueprint for the development of a plethora of metal catalyzed reactions of typically inert amide bonds via acyl-metal intermediates. A unified strategy for amide bond activation to enable metal insertion into N-C amide bond is outlined ().

  5. Mechanisms of bacterially catalyzed reductive dehalogenation

    Picardal, Flynn William [Univ. of Arizona, Tucson, AZ (United States)

    1992-01-01

    Nine bacteria were tested for the ability to dehalogenate tetrachloromethane (CT), tetrachloroethene (PCE), and 1, 1, 1-trichloroethane (TCA) under anaerobic conditions. Three bacteria were able to reductively dehalogenate CT. Dehalogenation ability was not readily linked to a common metabolism or changes in culture redox potential. None of the bacteria tested were able to dehalogenate PCE or TCA. One of the bacteria capable of dehalogenating CT, Shewanella putrefaciens, was chosen as a model organism to study mechanisms of bacterially catalyzed reductive dehalogenation. The effect of a variety of alternate electron acceptors on CT dehalogenation ability by S. putrefaciens was determined. oxygen and nitrogen oxides were inhibitory but Fe (III), trimethylamine oxide, and fumarate were not. A model of the electron transport chain of S. putrefaciens was developed to explain inhibition patterns. A period of microaerobic growth prior to CT exposure increased the ability of S. putrefaciens to dehalogenate CT. A microaerobic growth period also increased cytochrome concentrations. A relationship between cytochrome content and dehalogenation ability was developed from studies in which cytochrome concentrations in S. putrefaciens were manipulated by changing growth conditions. Stoichiometry studies using 14C-CT suggested that CT was first reduced to form a trichloromethyl radical. Reduction of the radical to produce chloroform and reaction of the radical with cellular biochemicals explained observed product distributions. Carbon dioxide or other fully dehalogenated products were not found.

  6. Impact of fatty acyl composition and quantity of triglycerides on bioaccessibility of dietary carotenoids.

    Huo, Tianyao; Ferruzzi, Mario G; Schwartz, Steven J; Failla, Mark L

    2007-10-31

    A carotenoid-rich salad meal with varying amounts and types of triglycerides (TG) was digested using simulated gastric and small intestinal conditions. Xanthophylls (lutein and zeaxanthin) and carotenes (alpha-carotene, beta-carotene, and lycopene) in chyme and micelle fraction were quantified to determine digestive stability and efficiency of micellarization (bioaccessibility). Micellarization of lutein (+zeaxanthin) exceeded that of alpha- and beta-carotenes, which was greater than that of lycopene for all test conditions. Micellarization of carotenes, but not lutein (+zeaxanthin), was enhanced (P structured TG (c18:1 > c8:0 > c4:0). The degree of unsaturation of c18 fatty acyl chains in TG added to the salad purée did not significantly alter the efficiency of micellarization of carotenoids. Relatively low amounts of triolein and canola oil (0.5-1%) were required for maximum micellarization of carotenes, but more oil (approximately 2.5%) was required when TG with medium chain saturated fatty acyl groups (e.g., trioctanoin and coconut oil) was added to the salad. Uptake of lutein and beta-carotene by Caco-2 cells also was examined by exposing cells to micelles generated during the simulated digestion of salad purée with either triolein or trioctanoin. Cell accumulation of beta-carotene was independent of fatty acyl composition of micelles, whereas lutein uptake was slightly, but significantly, increased from samples with digested triolein compared to trioctanoin. The results show that the in vitro transfer of alpha-carotene, beta-carotene, and lycopene from chyme to mixed micelles during digestion requires minimal (0.5-1%) lipid content in the meal and is affected by the length of fatty acyl chains but not the degree of unsaturation in TG. In contrast, fatty acyl chain length has limited if any impact on carotenoid uptake by small intestinal epithelial cells. These data suggest that the amount of TG in a typical meal does not limit the bioaccessibility of

  7. catalyzed oxidation of some amino acids by acid bromate

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    ABSTRACT: Kinetic investigations on Pd(II) catalyzed oxidation of dl-serine and dl- ... A suitable mechanism in agreement with observed kinetics has been ..... In acidic solution of potassium bromate quick .... Annual Review of Biochemistry.

  8. RNA-Catalyzed Polymerization and Replication of RNA

    Horning, D. P.; Samantha, B.; Tjhung, K. F.; Joyce, G. F.

    2017-07-01

    In an effort to reconstruct RNA-based life, in vitro evolution was used to obtain an RNA polymerase ribozyme that can synthesize a variety of complex functional RNAs and can catalyze the exponential amplification of short RNAs.

  9. FeBr3-catalyzed dibromination of alkenes and alkynes

    Yun Fa Zheng; Jian Yu; Guo Bing Yan; Xu Li; Song Luo

    2011-01-01

    The dibromination of alkenes and alkynes with bromosuccinimide and sodium bromide catalyzed by FeBr3 under mild conditions has been developed. The trans-dibromo compounds were exclusively obtained with excellent yields.

  10. catalyzed oxidation of formamidine derivative by hexacyanoferrate(III

    triazol-3-yl) formamidine (ATF) by hexacyanoferrate(III) (HCF) was studied spectrophotometrically in aqueous alkalinemedium. Both uncatalyzed and catalyzed reactions showed first order kinetics with respect to [HCF],whereas the reaction ...

  11. Biodiesel production from Jatropha curcas oil catalyzed by whole ...

    my mord

    2013-07-03

    Jul 3, 2013 ... catalyzed by whole cells of Aureobasidium pullulans var. melanogenum ... friendly and renewable fuel that can be used directly in diesel engines ... methanol (or supercritical ethanol) transesterification is not commercially ...

  12. Rhodium-Catalyzed Dehydrogenative Borylation of Cyclic Alkenes

    Kondoh, Azusa; Jamison, Timothy F.

    2010-01-01

    A rhodium-catalyzed dehydrogenative borylation of cyclic alkenes is described. This reaction provides direct access to cyclic 1-alkenylboronic acid pinacol esters, useful intermediates in organic synthesis. Suzuki-Miyaura cross-coupling applications are also presented. PMID:20107646

  13. catalyzed oxidation of formamidine derivative by hexacyanoferrate(III)

    Both uncatalyzed and catalyzed reactions showed first order kinetics with respect to [HCF], whereas ... The rate laws associated with the reaction mechanisms ... activation and thermodynamic parameters have been computed and discussed.

  14. The presence of acylated ghrelin during in vitro maturation of bovine oocytes induces cumulus cell DNA damage and apoptosis, and impairs early embryo development.

    Sirini, Matias A; Anchordoquy, Juan Mateo; Anchordoquy, Juan Patricio; Pascua, Ana M; Nikoloff, Noelia; Carranza, Ana; Relling, Alejandro E; Furnus, Cecilia C

    2017-10-01

    The aim of this study was to investigate the effects of acylated ghrelin supplementation during in vitro maturation (IVM) of bovine oocytes. IVM medium was supplemented with 20, 40 or 60 pM acylated ghrelin concentrations. Cumulus expansion area and oocyte nuclear maturation were studied as maturation parameters. Cumulus-oocyte complexes (COC) were assessed with the comet, apoptosis and viability assays. The in vitro effects of acylated ghrelin on embryo developmental capacity and embryo quality were also evaluated. Results demonstrated that acylated ghrelin did not affect oocyte nuclear maturation and cumulus expansion area. However, it induced cumulus cell (CC) death, apoptosis and DNA damage. The damage increased as a function of the concentration employed. Additionally, the percentages of blastocyst yield, hatching and embryo quality decreased with all acylated ghrelin concentrations tested. Our study highlights the importance of acylated ghrelin in bovine reproduction, suggesting that this metabolic hormone could function as a signal that prevents the progress to reproductive processes.

  15. Concentrations of long-chain acyl-acyl carrier proteins during fatty acid synthesis by chloroplasts isolated from pea (Pisum sativum), safflower (Carthamus tinctoris), and amaranthus (Amaranthus lividus) leaves

    Roughan, G.; Nishida, I.

    1990-01-01

    Fatty acid synthesis from [1-14C]acetate by chloroplasts isolated from peas and amaranthus was linear for at least 15 min, whereas incorporation of the tracer into long-chain acyl-acyl carrier protein (ACP) did not increase after 2-3 min. When reactions were transferred to the dark after 3-5 min, long-chain acyl-ACPs lost about 90% of their radioactivity and total fatty acids retained all of theirs. Half-lives of the long-chain acyl-ACPs were estimated to be 10-15 s. Concentrations of palmitoyl-, stearoyl-, and oleoyl-ACP as indicated by equilibrium labeling during steady-state fatty acid synthesis, ranged from 0.6-1.1, 0.2-0.7, and 0.4-1.6 microM, respectively, for peas and from 1.6-1.9, 1.3-2.6, and 0.6-1.4 microM, respectively, for amaranthus. These values are based on a chloroplast volume of 47 microliters/mg chlorophyll and varied according to the mode of the incubation. A slow increase in activity of the fatty acid synthetase in safflower chloroplasts resulted in long-chain acyl-ACPs continuing to incorporate labeled acetate for 10 min. Upon re-illumination following a dark break, however, both fatty acid synthetase activity and acyl-ACP concentrations increased very rapidly. Palmitoyl-ACP was present at concentrations up to 2.5 microM in safflower chloroplasts, whereas those of stearoyl- and oleoyl-ACPs were in the lower ranges measured for peas. Acyl-ACPs were routinely separated from extracts of chloroplasts that had been synthesising long-chain fatty acids from labeled acetate by a minor modification of the method of Mancha et al. The results compared favorably with those obtained using alternative analytical methods such as adsorption to filter paper and partition chromatography on silicic acid columns

  16. Rhenium and Manganese-Catalyzed Selective Alkenylation of Indoles

    Wang, Chengming

    2018-04-06

    An efficient rhenium‐catalyzed regioselective C‐H bond alkenylation of indoles is reported. The protocol operates well for internal as well as terminal alkynes, affording products in good to excellent yields. Furthermore, a manganese catalyzed, acid free, regioselective C2‐alkenylation of indoles with internal alkynes is described. The directing groups can be easily removed after the reaction and the resulting products can be used as valuable building blocks for the synthesis of diverse heterocyclic compounds.

  17. Toward Efficient Palladium-Catalyzed Allylic C-H Alkylation

    Jensen, Thomas; Fristrup, Peter

    2009-01-01

    Recent breakthroughs have proved that direct palladium (II)-catalyzed allylic C-H alkylation can be achieved. This new procedure shows that the inherent requirement for a leaving group in the Tsuji-Trost palladium-catalyzed allylic alkylation can be lifted. These initial reports hold great promise...... for the development of allylic C-H alkylation into a widely applicable methodology, thus providing a means to enhance synthetic efficiency in these reactions....

  18. Rhenium and Manganese-Catalyzed Selective Alkenylation of Indoles

    Wang, Chengming; Rueping, Magnus

    2018-01-01

    An efficient rhenium‐catalyzed regioselective C‐H bond alkenylation of indoles is reported. The protocol operates well for internal as well as terminal alkynes, affording products in good to excellent yields. Furthermore, a manganese catalyzed, acid free, regioselective C2‐alkenylation of indoles with internal alkynes is described. The directing groups can be easily removed after the reaction and the resulting products can be used as valuable building blocks for the synthesis of diverse heterocyclic compounds.

  19. 40 CFR 721.10055 - 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-soya acyl derivs., inner salts.

    2010-07-01

    ...-(carboxymethyl)-N,N-dimethyl-, N-soya acyl derivs., inner salts. 721.10055 Section 721.10055 Protection of...-amino-N-(carboxymethyl)-N,N-dimethyl-, N-soya acyl derivs., inner salts. (a) Chemical substance and...-(carboxymethyl)-N,N-dimethyl-, N-soya acyl derivs., inner salts (PMN P-03-46; CAS No. 136504-87-5) is subject to...

  20. 3-Sulfinopropionyl-coenzyme A (3SP-CoA) desulfinase from Advenella mimigardefordensis DPN7T: crystal structure and function of a desulfinase with an acyl-CoA dehydrogenase fold

    Schürmann, Marc; Meijers, Rob; Schneider, Thomas R.; Steinbüchel, Alexander; Cianci, Michele

    2015-01-01

    3-Sulfinopropionyl-coenzyme A (3SP-CoA) desulfinase (AcdDPN7; EC 3.13.1.4) was identified during investigation of the 3,3′-dithiodipropionic acid (DTDP) catabolic pathway in the betaproteobacterium Advenella mimigardefordensis strain DPN7T. DTDP is an organic disulfide and a precursor for the synthesis of polythioesters (PTEs) in bacteria, and is of interest for biotechnological PTE production. AcdDPN7 catalyzes sulfur abstraction from 3SP-CoA, a key step during the catabolism of DTDP. Here, the crystal structures of apo AcdDPN7 at 1.89 Å resolution and of its complex with the CoA moiety from the substrate analogue succinyl-CoA at 2.30 Å resolution are presented. The apo structure shows that AcdDPN7 belongs to the acyl-CoA dehydrogenase superfamily fold and that it is a tetramer, with each subunit containing one flavin adenine dinucleotide (FAD) molecule. The enzyme does not show any dehydrogenase activity. Dehydrogenase activity would require a catalytic base (Glu or Asp residue) at either position 246 or position 366, where a glutamine and a glycine are instead found, respectively, in this desulfinase. The positioning of CoA in the crystal complex enabled the modelling of a substrate complex containing 3SP-CoA. This indicates that Arg84 is a key residue in the desulfination reaction. An Arg84Lys mutant showed a complete loss of enzymatic activity, suggesting that the guanidinium group of the arginine is essential for desulfination. AcdDPN7 is the first desulfinase with an acyl-CoA dehydrogenase fold to be reported, which underlines the versatility of this enzyme scaffold. PMID:26057676