Science.gov

Sample records for acid amides including

  1. Diaminopimelic Acid Amidation in Corynebacteriales

    PubMed Central

    Levefaudes, Marjorie; Patin, Delphine; de Sousa-d'Auria, Célia; Chami, Mohamed; Blanot, Didier; Hervé, Mireille; Arthur, Michel; Houssin, Christine; Mengin-Lecreulx, Dominique

    2015-01-01

    A gene named ltsA was earlier identified in Rhodococcus and Corynebacterium species while screening for mutations leading to increased cell susceptibility to lysozyme. The encoded protein belonged to a huge family of glutamine amidotransferases whose members catalyze amide nitrogen transfer from glutamine to various specific acceptor substrates. We here describe detailed physiological and biochemical investigations demonstrating the specific role of LtsA protein from Corynebacterium glutamicum (LtsACg) in the modification by amidation of cell wall peptidoglycan diaminopimelic acid (DAP) residues. A morphologically altered but viable ΔltsA mutant was generated, which displays a high susceptibility to lysozyme and β-lactam antibiotics. Analysis of its peptidoglycan structure revealed a total loss of DAP amidation, a modification that was found in 80% of DAP residues in the wild-type polymer. The cell peptidoglycan content and cross-linking were otherwise not modified in the mutant. Heterologous expression of LtsACg in Escherichia coli yielded a massive and toxic incorporation of amidated DAP into the peptidoglycan that ultimately led to cell lysis. In vitro assays confirmed the amidotransferase activity of LtsACg and showed that this enzyme used the peptidoglycan lipid intermediates I and II but not, or only marginally, the UDP-MurNAc pentapeptide nucleotide precursor as acceptor substrates. As is generally the case for glutamine amidotransferases, either glutamine or NH4+ could serve as the donor substrate for LtsACg. The enzyme did not amidate tripeptide- and tetrapeptide-truncated versions of lipid I, indicating a strict specificity for a pentapeptide chain length. PMID:25847251

  2. 40 CFR 721.10680 - Fatty acid amides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amides (generic). 721.10680... Substances § 721.10680 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as fatty acid amides (PMNs...

  3. 40 CFR 721.10686 - Fatty acid amides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amides (generic). 721.10686... Substances § 721.10686 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as fatty acid amides (PMNs...

  4. 40 CFR 721.10691 - Fatty acid amide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amide (generic). 721.10691... Substances § 721.10691 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-13-267) is...

  5. 40 CFR 721.10320 - Fatty acid amide (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Fatty acid amide (generic). 721.10320... Substances § 721.10320 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-03-186) is...

  6. 40 CFR 721.10687 - Fatty acid amide hydrochlorides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amide hydrochlorides... Specific Chemical Substances § 721.10687 Fatty acid amide hydrochlorides (generic). (a) Chemical substance... fatty acid amide hydrochlorides (PMNs P-13-201, P-13-203, P-13-204, P-13-205, P-13-206, P-13-207,...

  7. 40 CFR 721.10320 - Fatty acid amide (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amide (generic). 721.10320... Substances § 721.10320 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-03-186) is...

  8. 40 CFR 721.10463 - Fatty acid amides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amides (generic). 721.10463... Substances § 721.10463 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amides (PMN...

  9. 40 CFR 721.10320 - Fatty acid amide (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid amide (generic). 721.10320... Substances § 721.10320 Fatty acid amide (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amide (PMN P-03-186) is...

  10. 40 CFR 721.10463 - Fatty acid amides (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid amides (generic). 721.10463... Substances § 721.10463 Fatty acid amides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as fatty acid amides (PMN...

  11. 40 CFR 721.10682 - Fatty acid amide hydrochlorides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid amide hydrochlorides... Specific Chemical Substances § 721.10682 Fatty acid amide hydrochlorides (generic). (a) Chemical substances... fatty acid amide hydrochlorides (PMNs P-13-63, P-13-64, P-13-65, P-13-69, P-13-70, P-13-71, P-13-72,...

  12. 40 CFR 721.10512 - Fatty acid maleic acid amides (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acid maleic acid amides (generic... Specific Chemical Substances § 721.10512 Fatty acid maleic acid amides (generic). (a) Chemical substance... fatty acid maleic acid amides (PMNs P-07-563 and P-07-564) are subject to reporting under this...

  13. 40 CFR 721.10512 - Fatty acid maleic acid amides (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acid maleic acid amides (generic... Specific Chemical Substances § 721.10512 Fatty acid maleic acid amides (generic). (a) Chemical substance... fatty acid maleic acid amides (PMNs P-07-563 and P-07-564) are subject to reporting under this...

  14. Fatty acid amides from freshwater green alga Rhizoclonium hieroglyphicum.

    PubMed

    Dembitsky, V M; Shkrob, I; Rozentsvet, O A

    2000-08-01

    Freshwater green algae Rhizoclonium hieroglyphicum growing in the Ural Mountains were examined for their fatty acid amides using capillary gas chromatography-mass spectrometry (GC-MS). Eight fatty acid amides were identified by GC-MS. (Z)-9-octadecenamide was found to be the major component (2.26%).

  15. Fatty acid amides from freshwater green alga Rhizoclonium hieroglyphicum.

    PubMed

    Dembitsky, V M; Shkrob, I; Rozentsvet, O A

    2000-08-01

    Freshwater green algae Rhizoclonium hieroglyphicum growing in the Ural Mountains were examined for their fatty acid amides using capillary gas chromatography-mass spectrometry (GC-MS). Eight fatty acid amides were identified by GC-MS. (Z)-9-octadecenamide was found to be the major component (2.26%). PMID:11014298

  16. Novel inhibitors of fatty acid amide hydrolase.

    PubMed

    Sit, S Y; Conway, Charlie; Bertekap, Robert; Xie, Kai; Bourin, Clotilde; Burris, Kevin; Deng, Hongfeng

    2007-06-15

    A class of bisarylimidazole derivatives are identified as potent inhibitors of the enzyme fatty acid amide hydrolase (FAAH). Compound 17 (IC(50)=2 nM) dose-dependently (0.1-10mg/kg, iv) potentiates the effects of exogenous anandamide (1 mg/kg, iv) in a rat thermal escape test (Hargreaves test), and shows robust antinociceptive activity in animal models of persistent (formalin test) and neuropathic (Chung model) pain. Compound 17 (20 mg/kg, iv) demonstrates activity in the formalin test that is comparable to morphine (3mg/kg, iv), and is dose-dependently inhibited by the CB1 antagonist SR141716A. In the Chung model, compound 17 shows antineuropathic effects similar to high-dose (100 mg/kg) gabapentin. FAAH inhibition shows potential utility for the clinical treatment of persistent and neuropathic pain.

  17. Treatment of Bile Acid Amidation Defects with Glycocholic Acid

    PubMed Central

    Heubi, James E.; Setchell, Kenneth D.R.; Jha, Pinky; Buckley, Donna; Zhang, Wujuan; Rosenthal, Philip; Potter, Carol; Horslen, Simon; Suskind, David

    2014-01-01

    Bile acid amidation defects were predicted to present with fat/fat soluble vitamin malabsorption with minimal cholestasis. We identified and treated 5 patients (1 male/4 females) from 4 families with defective bile acid amidation due to a genetically confirmed deficiency in bile acid CoA:amino acid N-acyl transferase (BAAT) with the conjugated bile acid, glycocholic acid (GCA). Fast atom bombardment-mass spectrometry analysis of urine and bile at baseline revealed predominantly unconjugated cholic acid and absence of the usual glycine and taurine conjugated primary bile acids. Treatment with 15 mg/kg GCA resulted in total duodenal bile acid concentrations of 23.3 ± 19.1 mmol/L (mean ± SD) and 63.5 ± 4.0% of the bile acids were secreted in bile in the conjugated form of which GCA represented 59.6 ± 9.3% of the total biliary bile acids. Unconjugated cholic acid continued to be present in high concentrations in bile because of partial intestinal deconjugation of orally administered GCA. Serum total bile acid concentrations did not significantly differ between pretreatment and post-treatment samples and serum contained predominantly unconjugated cholic acid. These findings confirmed efficient intestinal absorption, hepatic extraction and biliary secretion of the administered GCA. Oral tolerance tests for vitamin D2 (1000 IU vitamin D2/kg) and tocopherol (100 IU/kg tocopherol acetate) demonstrated improvement in fat-soluble vitamin absorption after GCA treatment. Growth improved in 3/3 growth-delayed prepubertal patients. Conclusions: Oral glycocholic acid therapy is safe and effective in improving growth and fat-soluble vitamin absorption in children and adolescents with inborn errors of bile acid metabolism due to amidation defects. PMID:25163551

  18. Acidizing using N-vinyl lactum/unsaturated amide copolymers

    SciTech Connect

    Burns, L.D.; Stahl, G.A.

    1987-09-01

    A process is described for acidizing a subterranean formation penetrated by at least one well comprising injecting into the formation, without a crosslinking agent, a water soluble thickened acid composition comprising: (1) water; (2) acid; and (3) a linear copolymer prepared from the monomers consisting of a N-vinyl lactam monomer and an alpha, beta-unsaturated amide monomer.

  19. Synthesis and antituberculosis activity of new fatty acid amides.

    PubMed

    D'Oca, Caroline Da Ros Montes; Coelho, Tatiane; Marinho, Tamara Germani; Hack, Carolina Rosa Lopes; Duarte, Rodrigo da Costa; da Silva, Pedro Almeida; D'Oca, Marcelo Gonçalves Montes

    2010-09-01

    This work reports the synthesis of new fatty acid amides from C16:0, 18:0, 18:1, 18:1 (OH), and 18:2 fatty acids families with cyclic and acyclic amines and demonstrate for the first time the activity of these compounds as antituberculosis agents against Mycobacterium tuberculosis H(37)Rv, M. tuberculosis rifampicin resistance (ATCC 35338), and M. tuberculosis isoniazid resistance (ATCC 35822). The fatty acid amides derivate from ricinoleic acid were the most potent one among a series of tested compounds, with a MIC 6.25 microg/mL for resistance strains.

  20. Process for chemical reaction of amino acids and amides yielding selective conversion products

    DOEpatents

    Holladay, Jonathan E.

    2006-05-23

    The invention relates to processes for converting amino acids and amides to desirable conversion products including pyrrolidines, pyrrolidinones, and other N-substituted products. L-glutamic acid and L-pyroglutamic acid provide general reaction pathways to numerous and valuable selective conversion products with varied potential industrial uses.

  1. New Umami Amides: Structure-Taste Relationship Studies of Cinnamic Acid Derived Amides and the Natural Occurrence of an Intense Umami Amide in Zanthoxylum piperitum.

    PubMed

    Frerot, Eric; Neirynck, Nathalie; Cayeux, Isabelle; Yuan, Yoyo Hui-Juan; Yuan, Yong-Ming

    2015-08-19

    A series of aromatic amides were synthesized from various acids and amines selected from naturally occurring structural frameworks. These synthetic amides were evaluated for umami taste in comparison with monosodium glutamate. The effect of the substitution pattern of both the acid and the amine parts on umami taste was investigated. The only intensely umami-tasting amides were those made from 3,4-dimethoxycinnamic acid. The amine part was more tolerant to structural changes. Amides bearing an alkyl- or alkoxy-substituted phenylethylamine residue displayed a clean umami taste as 20 ppm solutions in water. Ultraperformance liquid chromatography coupled with a high quadrupole-Orbitrap mass spectrometer (UPLC/MS) was subsequently used to show the natural occurrence of these amides. (E)-3-(3,4-Dimethoxyphenyl)-N-(4-methoxyphenethyl)acrylamide was shown to occur in the roots and stems of Zanthoxylum piperitum, a plant of the family Rutaceae growing in Korea, Japan, and China.

  2. Advances in the chemistry of sulphenic acid amides

    NASA Astrophysics Data System (ADS)

    Koval', I. V.

    1990-04-01

    Results of recent investigations in the area of sulphenic acid amides have been systematised and correlated in the review. Reactions of sulphenamides occurring with the generation of anions, radicals and nitrenes have been considered, as well as reactions accompanied by fussion of the S-N bond and oxidation of the sulphur atom. The bibliography contains 95 references.

  3. 40 CFR 721.10589 - Unsaturated fatty acids, amides with polyethylenepolyamine (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Unsaturated fatty acids, amides with... Specific Chemical Substances § 721.10589 Unsaturated fatty acids, amides with polyethylenepolyamine... identified generically as unsaturated fatty acids, amides with polyethylenepolyamine (PMN P-11-106)...

  4. 40 CFR 721.10590 - Fatty acids, amides with triethylentetramine (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fatty acids, amides with... Specific Chemical Substances § 721.10590 Fatty acids, amides with triethylentetramine (generic). (a... generically as fatty acids, amides with triethylentetramine (PMN P-11-107) is subject to reporting under...

  5. 40 CFR 721.10589 - Unsaturated fatty acids, amides with polyethylenepolyamine (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Unsaturated fatty acids, amides with... Specific Chemical Substances § 721.10589 Unsaturated fatty acids, amides with polyethylenepolyamine... identified generically as unsaturated fatty acids, amides with polyethylenepolyamine (PMN P-11-106)...

  6. 40 CFR 721.10590 - Fatty acids, amides with triethylentetramine (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fatty acids, amides with... Specific Chemical Substances § 721.10590 Fatty acids, amides with triethylentetramine (generic). (a... generically as fatty acids, amides with triethylentetramine (PMN P-11-107) is subject to reporting under...

  7. Retinobenzoic acids. 4. Conformation of aromatic amides with retinoidal activity. Importance of trans-amide structure for the activity.

    PubMed

    Kagechika, H; Himi, T; Kawachi, E; Shudo, K

    1989-10-01

    N-Methylation of two retinoidal amide compounds, 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benz oic acid (3, Am80) and 4-[[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)carbonyl]amino]benzoic acid (5, Am580), resulted in the disappearance of their potent differentiation-inducing activity on human promyelocytic leukemia cell line HL-60. Studies with 1H NMR and UV spectroscopy indicated that large conformational differences exist between the active secondary amides and the inactive N-methyl amides. From a comparison of the spectroscopic results of these amides with those of stilbene derivatives, the conformations of the active amides are expected to resemble that of (E)-stilbene, whereas the inactive amides resemble the Z isomer: 3 (Am80) and 5 (Am580) have a trans-amide bond and their whole structures are elongated, while the N-methylated compounds [4 (Am90) and 6 (Am590)] have a cis-amide bond, resulting in the folding of the two benzene rings. These structures in the crystals were related to those in solution by 13C NMR spectroscopic comparison between the two phases (solid and solution).

  8. Simple Amides of Oleanolic Acid as Effective Penetration Enhancers

    PubMed Central

    Bednarczyk-Cwynar, Barbara; Partyka, Danuta; Zaprutko, Lucjusz

    2015-01-01

    Transdermal transport is now becoming one of the most convenient and safe pathways for drug delivery. In some cases it is necessary to use skin penetration enhancers in order to allow for the transdermal transport of drugs that are otherwise insufficiently skin-permeable. A series of oleanolic acid amides as potential transdermal penetration enhancers was formed by multistep synthesis and the synthesis of all newly prepared compounds is presented. The synthetized amides of oleanolic acid were tested for their in vitro penetration promoter activity. The above activity was evaluated by means of using the Fürst method. The relationships between the chemical structure of the studied compounds and penetration activity are presented. PMID:26010090

  9. Accumulation of hydroxycinnamic acid amides in winter wheat under snow.

    PubMed

    Jin, Shigeki; Yoshida, Midori; Nakajima, Takashi; Murai, Akio

    2003-06-01

    It was found that the content of antifungal compounds p-coumaroylagmatine [1-(trans-4'-hydroxycinnamoylamino)-4-guanidinobutane] and p-coumaroyl-3-hydroxyagmatine [1-(trans-4'-hydroxycinnamoylamino)-3-hydroxy-4-guanidinobutane] in the crown of winter wheat (Triticum aestivum L. cv Chihokukomugi) significantly increased under snow cover. This finding suggests that the accumulation of these hydroxycinnamic acid amides was caused by winter stress and related to protecting the plant against snow mold under snow cover.

  10. Toxocara canis: Larvicidal activity of fatty acid amides.

    PubMed

    Mata-Santos, Taís; D'Oca, Caroline da Ros Montes; Mata-Santos, Hílton Antônio; Fenalti, Juliana; Pinto, Nitza; Coelho, Tatiane; Berne, Maria Elisabeth; da Silva, Pedro Eduardo Almeida; D'Oca, Marcelo Gonçalves Montes; Scaini, Carlos James

    2016-02-01

    Considering the therapeutic potential of fatty acid amides, the present study aimed to evaluate their in vitro activity against Toxocara canis larvae and their cytotoxicity for the first time. Linoleylpyrrolidilamide was the most potent, with a minimal larvicidal concentration (MLC) of 0.05 mg/mL and 27% cytotoxicity against murine peritoneal macrophages C57BL/6 mice, as assessed by the MTT assay. PMID:26783180

  11. Chemoselective esterification and amidation of carboxylic acids with imidazole carbamates and ureas.

    PubMed

    Heller, Stephen T; Sarpong, Richmond

    2010-10-15

    Imidazole carbamates and ureas were found to be chemoselective esterification and amidation reagents. A wide variety of carboxylic acids were converted to their ester or amide analogues by a simple synthetic procedure in high yields.

  12. Antiproliferative activity of synthetic fatty acid amides from renewable resources.

    PubMed

    dos Santos, Daiane S; Piovesan, Luciana A; D'Oca, Caroline R Montes; Hack, Carolina R Lopes; Treptow, Tamara G M; Rodrigues, Marieli O; Vendramini-Costa, Débora B; Ruiz, Ana Lucia T G; de Carvalho, João Ernesto; D'Oca, Marcelo G Montes

    2015-01-15

    In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line-the most aggressive CNS cancer.

  13. MATE Transporter-Dependent Export of Hydroxycinnamic Acid Amides.

    PubMed

    Dobritzsch, Melanie; Lübken, Tilo; Eschen-Lippold, Lennart; Gorzolka, Karin; Blum, Elke; Matern, Andreas; Marillonnet, Sylvestre; Böttcher, Christoph; Dräger, Birgit; Rosahl, Sabine

    2016-02-01

    The ability of Arabidopsis thaliana to successfully prevent colonization by Phytophthora infestans, the causal agent of late blight disease of potato (Solanum tuberosum), depends on multilayered defense responses. To address the role of surface-localized secondary metabolites for entry control, droplets of a P. infestans zoospore suspension, incubated on Arabidopsis leaves, were subjected to untargeted metabolite profiling. The hydroxycinnamic acid amide coumaroylagmatine was among the metabolites secreted into the inoculum. In vitro assays revealed an inhibitory activity of coumaroylagmatine on P. infestans spore germination. Mutant analyses suggested a requirement of the p-coumaroyl-CoA:agmatine N4-p-coumaroyl transferase ACT for the biosynthesis and of the MATE transporter DTX18 for the extracellular accumulation of coumaroylagmatine. The host plant potato is not able to efficiently secrete coumaroylagmatine. This inability is overcome in transgenic potato plants expressing the two Arabidopsis genes ACT and DTX18. These plants secrete agmatine and putrescine conjugates to high levels, indicating that DTX18 is a hydroxycinnamic acid amide transporter with a distinct specificity. The export of hydroxycinnamic acid amides correlates with a decreased ability of P. infestans spores to germinate, suggesting a contribution of secreted antimicrobial compounds to pathogen defense at the leaf surface. PMID:26744218

  14. Selective formation of secondary amides via the copper-catalyzed cross-coupling of alkylboronic acids with primary amides.

    PubMed

    Rossi, Steven A; Shimkin, Kirk W; Xu, Qun; Mori-Quiroz, Luis M; Watson, Donald A

    2013-05-01

    For the first time, a general catalytic procedure for the cross-coupling of primary amides and alkylboronic acids is demonstrated. The key to the success of this reaction was the identification of a mild base (NaOSiMe3) and oxidant (di-tert-butyl peroxide) to promote the copper-catalyzed reaction in high yield. This transformation provides a facile, high-yielding method for the monoalkylation of amides. PMID:23611591

  15. Drosophila melanogaster as a model system to study long-chain fatty acid amide metabolism

    PubMed Central

    Jeffries, Kristen A.; Dempsey, Daniel R.; Behari, Anita L.; Anderson, Ryan L.; Merkler, David J.

    2014-01-01

    Long-chain fatty acid amides are cell-signaling lipids identified in mammals and, recently, in invertebrates, as well. Many details regarding fatty acid amide metabolism remain unclear. Herein, we demonstrate that Drosophila melanogaster is an excellent model system for the study long-chain fatty acid amide metabolism as we have quantified the endogenous levels of N-acylglycines, N-acyldopamines, N-acylethanolamines, and primary fatty acid amides by LC/QTOF-MS. Growth of Drosophila melanogaster on media supplemented with [1-13C]-palmitate lead to a family of 13C-palmitate-labeled fatty acid amides in the fly heads. The [1-13C]-palmitate feeding studies provide insight into the biosynthesis of the fatty acid amides. PMID:24650760

  16. Instability of Amide Bond Comprising the 2-Aminotropone Moiety: Cleavable under Mild Acidic Conditions.

    PubMed

    Balachandra, Chenikkayala; Sharma, Nagendra K

    2015-08-21

    An unusual hydrolysis/solvolysis of the classical acyclic amide bond, derived from N-troponylaminoethylglycine (Traeg) and α-amino acids, is described under mild acidic conditions. The reactivity of this amide bond is possibly owed to the protonation of the troponyl carbonyl functional group. The results suggest that the Traeg amino acid is a potential candidate for protecting and caging of the amine functional group of bioactive molecules via a cleavable amide bond.

  17. Iodine-Catalyzed Decarboxylative Amidation of β,γ-Unsaturated Carboxylic Acids with Chloramine Salts Leading to Allylic Amides.

    PubMed

    Kiyokawa, Kensuke; Kojima, Takumi; Hishikawa, Yusuke; Minakata, Satoshi

    2015-10-26

    The iodine-catalyzed decarboxylative amidation of β,γ-unsaturated carboxylic acids with chloramine salts is described. This method enables the regioselective synthesis of allylic amides from various types of β,γ-unsaturated carboxylic acids containing substituents at the α- and β-positions. In the reaction, N-iodo-N-chloroamides, generated by the reaction of a chloramine salt with I2 , function as a key active species. The reaction provides an attractive alternative to existing methods for the synthesis of useful secondary allylic amine derivatives. PMID:26493878

  18. Lipase-catalyzed synthesis of fatty acid amide (erucamide) using fatty acid and urea.

    PubMed

    Awasthi, Neeraj Praphulla; Singh, R P

    2007-01-01

    Ammonolysis of fatty acids to the corresponding fatty acid amides is efficiently catalysed by Candida antartica lipase (Novozym 435). In the present paper lipase-catalysed synthesis of erucamide by ammonolysis of erucic acid and urea in organic solvent medium was studied and optimal conditions for fatty amides synthesis were established. In this process erucic acid gave 88.74 % pure erucamide after 48 hour and 250 rpm at 60 degrees C with 1:4 molar ratio of erucic acid and urea, the organic solvent media is 50 ml tert-butyl alcohol (2-methyl-2-propanol). This process for synthesis is economical as we used urea in place of ammonia or other amidation reactant at atmospheric pressure. The amount of catalyst used is 3 %.

  19. Lipase-catalyzed synthesis of fatty acid amide (erucamide) using fatty acid and urea.

    PubMed

    Awasthi, Neeraj Praphulla; Singh, R P

    2007-01-01

    Ammonolysis of fatty acids to the corresponding fatty acid amides is efficiently catalysed by Candida antartica lipase (Novozym 435). In the present paper lipase-catalysed synthesis of erucamide by ammonolysis of erucic acid and urea in organic solvent medium was studied and optimal conditions for fatty amides synthesis were established. In this process erucic acid gave 88.74 % pure erucamide after 48 hour and 250 rpm at 60 degrees C with 1:4 molar ratio of erucic acid and urea, the organic solvent media is 50 ml tert-butyl alcohol (2-methyl-2-propanol). This process for synthesis is economical as we used urea in place of ammonia or other amidation reactant at atmospheric pressure. The amount of catalyst used is 3 %. PMID:17898456

  20. Metal amides as the simplest acid/base catalysts for stereoselective carbon-carbon bond-forming reactions.

    PubMed

    Yamashita, Yasuhiro; Kobayashi, Shū

    2013-07-15

    In this paper, new possibilities for metal amides are described. Although typical metal amides are recognized as strong stoichiometric bases for deprotonation of inert or less acidic hydrogen atoms, transition-metal amides, namely silver and copper amides, show interesting abilities as one of the simplest acid/base catalysts in stereoselective carbon-carbon bond-forming reactions.

  1. Poly(ester amide)s based on (L)-lactic acid oligomers and α-amino acids: influence of the α-amino acid side chain in the poly(ester amide)s properties.

    PubMed

    Fonseca, Ana C; Coelho, Jorge F J; Valente, Joana F A; Correia, Tiago R; Correia, Ilídio J; Gil, Maria H; Simões, Pedro N

    2013-01-01

    Novel biodegradable and low cytotoxic poly(ester amide)s (PEAs) based on α-amino acids and (L)-lactic acid (L-LA) oligomers were successfully synthesized by interfacial polymerization. The chemical structure of the new polymers was confirmed by spectroscopic analyses. Further characterization suggests that the α-amino acid plays a critical role on the final properties of the PEA. L-phenylalanine provides PEAs with higher glass transition temperature, whereas glycine enhances the crystallinity. The hydrolytic degradation in PBS (pH = 7.4) at 37 °C also depends on the α-amino acid, being faster for glycine-based PEAs. The cytotoxic profiles using fibroblast human cells indicate that the PEAs did not elicit an acute cytotoxic effect. The strategy presented in this work opens the possibility of synthesizing biodegradable PEAs with low citotoxicity by an easy and fast method. It is worth to mention also that the properties of these materials can be fine-tuned only by changing the α-amino acid.

  2. [Activated Sludge Bacteria Transforming Cyanopyridines and Amides of Pyridinecarboxylic Acids].

    PubMed

    Demakov, V A; Vasil'ev, D M; Maksimova, Yu G; Pavlova, Yu A; Ovechkina, G V; Maksimov, A Yu

    2015-01-01

    Species diversity of bacteria from the activated sludge of Perm biological waste treatment facilities capable of transformation of cyanopyridines and amides of pyridinecarboxylic acids was investigated. Enrichment cultures in mineral media with 3-cyanopyridine as the sole carbon and nitrogen source were used to obtain 32 clones of gram-negative heterotrophic bacteria exhibiting moderate growth on solid and liquid media with 3- and 4-cyanopyridine. Sequencing of the 16S rRNA gene fragments revealed that the clones with homology of at least 99% belonged to the genera Acinetobacte, Alcaligenes, Delftia, Ochrobactrum, Pseudomonas, Stenotrophomonas, and Xanthobacter. PCR analysis showed that 13 out of 32 isolates contained the sequences (-1070 bp) homologous to the nitrilase genes reported previously in Alcaligenes faecalis JM3 (GenBank, D13419.1). Nine clones were capable of nitrile and amide transformation in minimal salt medium. Acinetobacter sp. 11 h and Alcaligenes sp. osv transformed 3-cyanopyridine to nicotinamide, while most of the clones possessed amidase activity (0.5 to 46.3 mmol/(g h) for acetamide and 0.1 to 5.6 mmol/(g h) for nicotinamide). Nicotinamide utilization by strain A. faecalis 2 was shown to result in excretion of a secondary metabolite, which was identified as dodecyl acrylate at 91% probability. PMID:26263697

  3. One-pot synthesis of polyunsaturated fatty acid amides with anti-proliferative properties.

    PubMed

    Tremblay, Hugo; St-Georges, Catherine; Legault, Marc-André; Morin, Caroline; Fortin, Samuel; Marsault, Eric

    2014-12-15

    A one-pot environmentally friendly transamidation of ω-3 fatty acid ethyl esters to amides and mono- or diacylglycerols was investigated via the use of a polymer-supported lipase. The method was used to synthesize a library of fatty acid monoglyceryl esters and amides. These new derivatives were found to have potent growth inhibition effects against A549 lung cancer cells.

  4. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  5. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  6. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  7. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  8. 40 CFR 721.720 - Alkoxylated fatty acid amide, alkylsulfate salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., alkylsulfate salt. 721.720 Section 721.720 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.720 Alkoxylated fatty acid amide, alkylsulfate salt. (a) Chemical... as an alkoxylated fatty acid amide, alkylsulfate salt (PMN P-97-136) is subject to reporting...

  9. Investigation of the complex reaction coordinate of acid catalyzed amide hydrolysis from molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Zahn, Dirk

    2004-05-01

    The rate-determining step of acid catalyzed peptide hydrolysis is the nucleophilic attack of a water molecule to the carbon atom of the amide group. Therein the addition of the hydroxyl group to the amide carbon atom involves the association of a water molecule transferring one of its protons to an adjacent water molecule. The protonation of the amide nitrogen atom follows as a separate reaction step. Since the nucleophilic attack involves the breaking and formation of several bonds, the underlying reaction coordinate is rather complex. We investigate this reaction step from path sampling Car-Parrinello molecular dynamics simulations. This approach does not require the predefinition of reaction coordinates and is thus particularly suited for investigating reaction mechanisms. From our simulations the most relevant components of the reaction coordinate are elaborated. Though the C⋯O distance of the oxygen atom of the water molecule performing the nucleophilic attack and the corresponding amide carbon atom is a descriptor of the reaction progress, a complete picture of the reaction coordinate must include all three molecules taking part in the reaction. Moreover, the proton transfer is found to depend on favorable solvent configurations. Thus, also the arrangement of non-reacting, i.e. solvent water molecules needs to be considered in the reaction coordinate.

  10. Sulfonyl Fluoride Inhibitors of Fatty Acid Amide Hydrolase

    PubMed Central

    Alapafuja, Shakiru O.; Nikas, Spyros P.; Bharatan, Indu; Shukla, Vidyanand G.; Nasr, Mahmoud L.; Bowman, Anna L.; Zvonok, Nikolai; Li, Jing; Shi, Xiaomeng; Engen, John R.; Makriyannis, Alexandros

    2013-01-01

    Sulfonyl fluorides are known to inhibit esterases. Early work from our laboratory has identified hexadecyl sulfonylfluoride (AM374) as a potent in vitro and in vivo inhibitor of fatty acid amide hydrolase (FAAH). We now report on later generation sulfonyl fluoride analogs that exhibit potent and selective inhibition of FAAH. Using recombinant rat and human FAAH we show that 5-(4-hydroxyphenyl)pentanesulfonyl fluoride (AM3506) has similar inhibitory activity for both the rat and the human enzyme, while rapid dilution assays and mass spectrometry analysis suggest that the compound is a covalent modifier for FAAH and inhibits its action in an irreversible manner. Our SAR results are highlighted by molecular docking of key analogs. PMID:23083016

  11. The effect of pH on the toxicity of fatty acids and fatty acid amides to rainbow trout gill cells.

    PubMed

    Bertin, Matthew J; Voronca, Delia C; Chapman, Robert W; Moeller, Peter D R

    2014-01-01

    Harmful algal blooms (HABs) expose aquatic organisms to multiple physical and chemical stressors during an acute time period. Algal toxins themselves may be altered by water chemistry parameters affecting their bioavailability and resultant toxicity. The purpose of this study was to determine the effects of two abiotic parameters (pH, inorganic metal salts) on the toxicity of fatty acid amides and fatty acids, two classes of lipids produced by harmful algae, including the golden alga, Prymnesium parvum, that are toxic to aquatic organisms. Rainbow trout gill cells were used as a model of the fish gill and exposed to single compounds and mixtures of compounds along with variations in pH level and concentration of inorganic metal salts. We employed artificial neural networks (ANNs) and standard ANOVA statistical analysis to examine and predict the effects of these abiotic parameters on the toxicity of fatty acid amides and fatty acids. Our results demonstrate that increasing pH levels increases the toxicity of fatty acid amides and inhibits the toxicity of fatty acids. This phenomenon is reversed at lower pH levels. Exposing gill cells to complex mixtures of chemical factors resulted in dramatic increases in toxicity compared to tests of single compounds for both the fatty acid amides and fatty acids. These findings highlight the potential of physicochemical factors to affect the toxicity of chemicals released during algal blooms and demonstrate drastic differences in the effect of pH on fatty acid amides and fatty acids. PMID:24240104

  12. Synthesis and structural characterisation of amides from picolinic acid and pyridine-2,6-dicarboxylic acid

    PubMed Central

    Devi, Prarthana; Barry, Sarah M.; Houlihan, Kate M.; Murphy, Michael J.; Turner, Peter; Jensen, Paul; Rutledge, Peter J.

    2015-01-01

    Coupling picolinic acid (pyridine-2-carboxylic acid) and pyridine-2,6-dicarboxylic acid with N-alkylanilines affords a range of mono- and bis-amides in good to moderate yields. These amides are of interest for potential applications in catalysis, coordination chemistry and molecular devices. The reaction of picolinic acid with thionyl chloride to generate the acid chloride in situ leads not only to the N-alkyl-N-phenylpicolinamides as expected but also the corresponding 4-chloro-N-alkyl-N-phenylpicolinamides in the one pot. The two products are readily separated by column chromatography. Chlorinated products are not observed from the corresponding reactions of pyridine-2,6-dicarboxylic acid. X-Ray crystal structures for six of these compounds are described. These structures reveal a general preference for cis amide geometry in which the aromatic groups (N-phenyl and pyridyl) are cis to each other and the pyridine nitrogen anti to the carbonyl oxygen. Variable temperature 1H NMR experiments provide a window on amide bond isomerisation in solution. PMID:25954918

  13. Selective rhodium-catalyzed reduction of tertiary amides in amino acid esters and peptides.

    PubMed

    Das, Shoubhik; Li, Yuehui; Bornschein, Christoph; Pisiewicz, Sabine; Kiersch, Konstanze; Michalik, Dirk; Gallou, Fabrice; Junge, Kathrin; Beller, Matthias

    2015-10-12

    Efficient reduction of the tertiary amide bond in amino acid derivatives and peptides is described. Functional group selectivity has been achieved by applying a commercially available rhodium precursor and bis(diphenylphosphino)propane (dppp) ligand together with phenyl silane as a reductant. This methodology allows for specific reductive derivatization of biologically interesting peptides and offers straightforward access to a variety of novel peptide derivatives for chemical biology studies and potential pharmaceutical applications. The catalytic system tolerates a variety of functional groups including secondary amides, ester, nitrile, thiomethyl, and hydroxy groups. This convenient hydrosilylation reaction proceeds at ambient conditions and is operationally safe because no air-sensitive reagents or highly reactive metal hydrides are needed. PMID:26189442

  14. Selective rhodium-catalyzed reduction of tertiary amides in amino acid esters and peptides.

    PubMed

    Das, Shoubhik; Li, Yuehui; Bornschein, Christoph; Pisiewicz, Sabine; Kiersch, Konstanze; Michalik, Dirk; Gallou, Fabrice; Junge, Kathrin; Beller, Matthias

    2015-10-12

    Efficient reduction of the tertiary amide bond in amino acid derivatives and peptides is described. Functional group selectivity has been achieved by applying a commercially available rhodium precursor and bis(diphenylphosphino)propane (dppp) ligand together with phenyl silane as a reductant. This methodology allows for specific reductive derivatization of biologically interesting peptides and offers straightforward access to a variety of novel peptide derivatives for chemical biology studies and potential pharmaceutical applications. The catalytic system tolerates a variety of functional groups including secondary amides, ester, nitrile, thiomethyl, and hydroxy groups. This convenient hydrosilylation reaction proceeds at ambient conditions and is operationally safe because no air-sensitive reagents or highly reactive metal hydrides are needed.

  15. Immunomodulatory lipids in plants: plant fatty acid amides and the human endocannabinoid system.

    PubMed

    Gertsch, Jürg

    2008-05-01

    Since the discovery that endogenous lipid mediators show similar cannabimimetic effects as phytocannabinoids from CANNABIS SATIVA, our knowledge about the endocannabinoid system has rapidly expanded. Today, endocannabinoid action is known to be involved in various diseases, including inflammation and pain. As a consequence, the G-protein coupled cannabinoid receptors, endocannabinoid transport, as well as endocannabinoid metabolizing enzymes represent targets to block or enhance cannabinoid receptor-mediated signalling for therapeutic intervention. Based on the finding that certain endocannabinoid-like fatty acid N-alkylamides from purple coneflower ( ECHINACEA spp.) potently activate CB2 cannabinoid receptors we have focused our interest on plant fatty acid amides (FAAs) and their overall cannabinomodulatory effects. Certain FAAs are also able to partially inhibit the action of fatty acid amide hydrolase (FAAH), which controls the breakdown of endocannabinoids. Intriguingly, plants lack CB receptors and do not synthesize endocannabinoids, but express FAAH homologues capable of metabolizing plant endogenous N-acylethanolamines (NAEs). While the site of action of these NAEs in plants is unknown, endogenous NAEs and arachidonic acid glycerols in animals interact with distinct physiological lipid receptors, including cannabinoid receptors. There is increasing evidence that also plant FAAs other than NAEs can pharmacologically modulate the action of these endogenous lipid signals. The interference of plant FAAs with the animal endocannabinoid system could thus be a fortunate evolutionary cross point with yet unexplored therapeutic potential.

  16. Atom-economic catalytic amide synthesis from amines and carboxylic acids activated in situ with acetylenes

    PubMed Central

    Krause, Thilo; Baader, Sabrina; Erb, Benjamin; Gooßen, Lukas J.

    2016-01-01

    Amide bond-forming reactions are of tremendous significance in synthetic chemistry. Methodological research has, in the past, focused on efficiency and selectivity, and these have reached impressive levels. However, the unacceptable amounts of waste produced have led the ACS GCI Roundtable to label ‘amide bond formation avoiding poor atom economy' as the most pressing target for sustainable synthetic method development. In response to this acute demand, we herein disclose an efficient one-pot amide coupling protocol that is based on simple alkynes as coupling reagents: in the presence of a dichloro[(2,6,10-dodecatriene)-1,12-diyl]ruthenium catalyst, carboxylate salts of primary or secondary amines react with acetylene or ethoxyacetylene to vinyl ester intermediates, which undergo aminolysis to give the corresponding amides along only with volatile acetaldehyde or ethyl acetate, respectively. The new amide synthesis is broadly applicable to the synthesis of structurally diverse amides, including dipeptides. PMID:27282773

  17. Atom-economic catalytic amide synthesis from amines and carboxylic acids activated in situ with acetylenes.

    PubMed

    Krause, Thilo; Baader, Sabrina; Erb, Benjamin; Gooßen, Lukas J

    2016-01-01

    Amide bond-forming reactions are of tremendous significance in synthetic chemistry. Methodological research has, in the past, focused on efficiency and selectivity, and these have reached impressive levels. However, the unacceptable amounts of waste produced have led the ACS GCI Roundtable to label 'amide bond formation avoiding poor atom economy' as the most pressing target for sustainable synthetic method development. In response to this acute demand, we herein disclose an efficient one-pot amide coupling protocol that is based on simple alkynes as coupling reagents: in the presence of a dichloro[(2,6,10-dodecatriene)-1,12-diyl]ruthenium catalyst, carboxylate salts of primary or secondary amines react with acetylene or ethoxyacetylene to vinyl ester intermediates, which undergo aminolysis to give the corresponding amides along only with volatile acetaldehyde or ethyl acetate, respectively. The new amide synthesis is broadly applicable to the synthesis of structurally diverse amides, including dipeptides. PMID:27282773

  18. Evaluation of physicochemical properties, skin permeation and accumulation profiles of salicylic acid amide prodrugs as sunscreen agent.

    PubMed

    Yan, Yi-Dong; Sung, Jun Ho; Lee, Dong Won; Kim, Jung Sun; Jeon, Eun-Mi; Kim, Dae-Duk; Kim, Dong Wuk; Kim, Jong Oh; Piao, Ming Guan; Li, Dong Xun; Yong, Chul Soon; Choi, Han Gon

    2011-10-31

    Various amide prodrugs of salicylic acid were synthesised, and their physicochemical properties including lipophilicity, chemical stability and enzymatic hydrolysis were investigated. In vivo skin permeation and accumulation profiles were also evaluated using a combination of common permeation enhancing techniques such as the use of a supersaturated solution of permeants in an enhancer vehicle, a lipophilic receptor solution, removal of the stratum corneum and delipidisation of skin. Their capacity factor values were proportional to the degree of carbon-carbon saturation in the side chain. All these amides were highly stable in acetonitrile and glycerine. Amide prodrugs were converted to salicylic acid both in hairless mouse liver and skin homogenates. N-dodecyl salicylamide (C12SM) showed the lowest permeation of salicylic acid in skin compared to the other prodrugs, probably due to its low aqueous solubility. It had a high affinity for the stratum corneum and its accumulation was restricted to only the uppermost layer of skin. Thus, this amide prodrug could be a safer topical sunscreen agent with minimum potential for systemic absorption.

  19. Computational insights into function and inhibition of fatty acid amide hydrolase.

    PubMed

    Palermo, Giulia; Rothlisberger, Ursula; Cavalli, Andrea; De Vivo, Marco

    2015-02-16

    The Fatty Acid Amide Hydrolase (FAAH) enzyme is a membrane-bound serine hydrolase responsible for the deactivating hydrolysis of a family of naturally occurring fatty acid amides. FAAH is a critical enzyme of the endocannabinoid system, being mainly responsible for regulating the level of its main cannabinoid substrate anandamide. For this reason, pharmacological inhibition of FAAH, which increases the level of endogenous anandamide, is a promising strategy to cure a variety of diseases including pain, inflammation, and cancer. Much structural, mutagenesis, and kinetic data on FAAH has been generated over the last couple of decades. This has prompted several informative computational investigations to elucidate, at the atomic-level, mechanistic details on catalysis and inhibition of this pharmaceutically relevant enzyme. Here, we review how these computational studies - based on classical molecular dynamics, full quantum mechanics, and hybrid QM/MM methods - have clarified the binding and reactivity of some relevant substrates and inhibitors of FAAH. We also discuss the experimental implications of these computational insights, which have provided a thoughtful elucidation of the complex physical and chemical steps of the enzymatic mechanism of FAAH. Finally, we discuss how computations have been helpful for building structure-activity relationships of potent FAAH inhibitors. PMID:25240419

  20. Pharmaceuticals and Surfactants from Alga-Derived Feedstock: Amidation of Fatty Acids and Their Derivatives with Amino Alcohols.

    PubMed

    Tkacheva, Anastasia; Dosmagambetova, Inkar; Chapellier, Yann; Mäki-Arvela, Päivi; Hachemi, Imane; Savela, Risto; Leino, Reko; Viegas, Carolina; Kumar, Narendra; Eränen, Kari; Hemming, Jarl; Smeds, Annika; Murzin, Dmitry Yu

    2015-08-24

    Amidation of renewable feedstocks, such as fatty acids, esters, and Chlorella alga based biodiesel, was demonstrated with zeolites and mesoporous materials as catalysts and ethanolamine, alaninol, and leucinol. The last two can be derived from amino acids present in alga. The main products were fatty alkanol amides and the corresponding ester amines, as confirmed by NMR and IR spectroscopy. Thermal amidation of technical-grade oleic acid and stearic acid at 180 °C with ethanolamine were non-negligible; both gave 61% conversion. In the amidation of stearic acid with ethanolamine, the conversion over H-Beta-150 was 80% after 3 h, whereas only 63% conversion was achieved for oleic acid; this shows that a microporous catalyst is not suitable for this acid and exhibits a wrinkled conformation. The highest selectivity to stearoyl ethanolamide of 92% was achieved with mildly acidic H-MCM-41 at 70% conversion in 3 h at 180 °C. Highly acidic catalysts favored the formation of the ester amine, whereas the amide was obtained with a catalyst that exhibited an optimum acidity. The conversion levels achieved with different fatty acids in the range C12-C18 were similar; this shows that the fatty acid length does not affect the amidation rate. The amidation of methyl palmitate and biodiesel gave low conversions over an acidic catalyst, which suggested that the reaction mechanism in the amidation of esters was different.

  1. Pharmaceuticals and Surfactants from Alga-Derived Feedstock: Amidation of Fatty Acids and Their Derivatives with Amino Alcohols.

    PubMed

    Tkacheva, Anastasia; Dosmagambetova, Inkar; Chapellier, Yann; Mäki-Arvela, Päivi; Hachemi, Imane; Savela, Risto; Leino, Reko; Viegas, Carolina; Kumar, Narendra; Eränen, Kari; Hemming, Jarl; Smeds, Annika; Murzin, Dmitry Yu

    2015-08-24

    Amidation of renewable feedstocks, such as fatty acids, esters, and Chlorella alga based biodiesel, was demonstrated with zeolites and mesoporous materials as catalysts and ethanolamine, alaninol, and leucinol. The last two can be derived from amino acids present in alga. The main products were fatty alkanol amides and the corresponding ester amines, as confirmed by NMR and IR spectroscopy. Thermal amidation of technical-grade oleic acid and stearic acid at 180 °C with ethanolamine were non-negligible; both gave 61% conversion. In the amidation of stearic acid with ethanolamine, the conversion over H-Beta-150 was 80% after 3 h, whereas only 63% conversion was achieved for oleic acid; this shows that a microporous catalyst is not suitable for this acid and exhibits a wrinkled conformation. The highest selectivity to stearoyl ethanolamide of 92% was achieved with mildly acidic H-MCM-41 at 70% conversion in 3 h at 180 °C. Highly acidic catalysts favored the formation of the ester amine, whereas the amide was obtained with a catalyst that exhibited an optimum acidity. The conversion levels achieved with different fatty acids in the range C12-C18 were similar; this shows that the fatty acid length does not affect the amidation rate. The amidation of methyl palmitate and biodiesel gave low conversions over an acidic catalyst, which suggested that the reaction mechanism in the amidation of esters was different. PMID:26197759

  2. Fuel and lubricant additives from acid treated mixtures of vegetable oil derived amides and esters

    SciTech Connect

    Bonazza, B.R.; Devault, A.N.

    1981-05-26

    Vegetable oils such as corn oil, peanut oil, and soy oil are reacted with polyamines to form a mixture containing amides, imides, half esters, and glycerol with subsequent treatment with a strong acid such as sulfonic acid to produce a product mix that has good detergent properties in fuels and lubricants.

  3. N-glycosides of amino acid amides from Hemerocallis fulva var. sempervirens.

    PubMed

    Ogawa, Yuko; Konishi, Tenji

    2009-10-01

    As part of our search for sedative substances from natural sources, we isolated two novel amino acid amides connected with the fructopyranose, kwansonine A (1) and kwansonine B (2), together with three known amino acid amides, longitubanine A (3), longitubanine B (4), and pinnatanine (5), from Hemerocallis fulva L. var. sempervirens (ARAKI) M. HOTTA. The structures of 1 and 2 have been determined on the spectroscopic evidences as N(2)-(1-beta-D-fructopyranosyl)-N(5)-(2',5'-dihydro-2'-furyl-3'-hydroxymethyl)-gamma-hydroxyglutamine and N(2)-(1-beta-D-fructopyranosyl)-N(5)-(2-hydroxymethylbutadienyl)-gamma-hydroxyglutamine. This is the first report on the isolation of amino acid amide N-furctoside from Hemerocallis genus plant. PMID:19801868

  4. Choline Chloride Catalyzed Amidation of Fatty Acid Ester to Monoethanolamide: A Green Approach.

    PubMed

    Patil, Pramod; Pratap, Amit

    2016-01-01

    Choline chloride catalyzed efficient method for amidation of fatty acid methyl ester to monoethanolamide respectively. This is a solvent free, ecofriendly, 100% chemo selective and economically viable path for alkanolamide synthesis. The Kinetics of amidation of methyl ester were studied and found to be first order with respect to the concentration of ethanolamine. The activation energy (Ea) for the amidation of lauric acid methyl ester catalyzed by choline chloride was found to be 50.20 KJ mol(-1). The 98% conversion of lauric acid monoethanolamide was obtained at 110°C in 1 h with 6% weight of catalyst and 1:1.5 molar ratio of methyl ester to ethanolamine under nitrogen atmosphere. PMID:26666271

  5. Discovery and molecular basis of potent noncovalent inhibitors of fatty acid amide hydrolase (FAAH)

    PubMed Central

    Min, Xiaoshan; Thibault, Stephen T.; Porter, Amy C.; Gustin, Darin J.; Carlson, Timothy J.; Xu, Haoda; Lindstrom, Michelle; Xu, Guifen; Uyeda, Craig; Ma, Zhihua; Li, Yihong; Kayser, Frank; Walker, Nigel P. C.; Wang, Zhulun

    2011-01-01

    Fatty acid amide hydrolase (FAAH), an amidase-signature family member, is an integral membrane enzyme that degrades lipid amides including the endogenous cannabinoid anandamide and the sleep-inducing molecule oleamide. Both genetic knock out and pharmacological administration of FAAH inhibitors in rodent models result in analgesic, anxiolytic, and antiinflammatory phenotypes. Targeting FAAH activity, therefore, presents a promising new therapeutic strategy for the treatment of pain and other neurological-related or inflammatory disorders. Nearly all FAAH inhibitors known to date attain their binding potency through a reversible or irreversible covalent modification of the nucleophile Ser241 in the unusual Ser-Ser-Lys catalytic triad. Here, we report the discovery and mechanism of action of a series of ketobenzimidazoles as unique and potent noncovalent FAAH inhibitors. Compound 2, a representative of these ketobenzimidazoles, was designed from a series of ureas that were identified from high-throughput screening. While urea compound 1 is characterized as an irreversible covalent inhibitor, the cocrystal structure of FAAH complexed with compound 2 reveals that these ketobenzimidazoles, though containing a carbonyl moiety, do not covalently modify Ser241. These inhibitors achieve potent inhibition of FAAH activity primarily from shape complementarity to the active site and through numerous hydrophobic interactions. These noncovalent compounds exhibit excellent selectivity and good pharmacokinetic properties. The discovery of this distinctive class of inhibitors opens a new avenue for modulating FAAH activity through nonmechanism-based inhibition. PMID:21502526

  6. Melonoside A: An ω-Glycosylated Fatty Acid Amide from the Far Eastern Marine Sponge Melonanchora kobjakovae.

    PubMed

    Guzii, Alla G; Makarieva, Tatyana N; Denisenko, Vladimir A; Dmitrenok, Pavel S; Kuzmich, Aleksandra S; Dyshlovoy, Sergey A; von Amsberg, Gunhild; Krasokhin, Vladimir B; Stonik, Valentin A

    2016-07-15

    Melonoside A (1), the first representative of a new class of ω-glycosylated fatty acid amides, was isolated from the Far Eastern marine sponge Melonanchora kobjakovae. The structure of 1, including absolute configuration, was established using detailed analysis of 1D and 2D NMR, CD, and mass spectra as well as chemical transformations. Compound 1 induces autophagy of human cisplatin-resistant germinal tumor cells NCCIT-R. PMID:27358020

  7. A comparative study of the complexation of uranium(VI) withoxydiacetic acid and its amide derivatives

    SciTech Connect

    Rao, Linfeng; Tian, Guoxin

    2005-05-01

    There has been significant interest in recent years in the studies of alkyl-substituted amides as extractants for actinide separation because the products of radiolytic and hydrolytic degradation of amides are less detrimental to separation processes than those of organophosphorus compounds traditionally used in actinide separations. Stripping of actinides from the amide-containing organic solvents is relatively easy. In addition, the amide ligands are completely incinerable so that the amount of secondary wastes generated in nuclear waste treatment could be significantly reduced. One group of alkyl-substituted oxa-diamides have been shown to be promising in the separation of actinides from nuclear wastes. For example, tetraoctyl-3-oxa-glutaramide and tetraisobutyl-oxa-glutaramide form actinide complexes that can be effectively extracted from nitric acid solutions. To understand the thermodynamic principles governing the complexation of actinides with oxa-diamides, we have studied the complexation of U(VI) with dimethyl-3-oxa-glutaramic acid (DMOGA) and tetramethyl-3-oxa-glutaramide (TMOGA) in aqueous solutions, in comparison with oxydiacetic acid (ODA) (Figure 1). Previous studies have indicated that the complexation of U(VI) with ODA is strong and entropy-driven. Comparing the results for DMOGA and TMOGA with those for ODA could provide insight into the energetics of amide complexation with U(VI) and the relationship between the thermodynamic properties and the ligand structure.

  8. Complexation of di-amides of dipicolinic acid with neodymium

    SciTech Connect

    Lapka, J.L.; Paulenova, A.

    2013-07-01

    Di-amides have undergone significant studies as possible ligands for use in the partitioning of trivalent minor actinides and lanthanides. The binding affinities of three isomeric ligands with neodymium in acetonitrile solution have been investigated. The stability constants of the metal-ligand complexes formed between different isomers of N,N'-diethyl-N,N'- ditolyl-di-picolinamide (EtTDPA) and trivalent neodymium in acetonitrile have been determined by spectrophotometric and calorimetric methods. Each isomer of EtTDPA has been found to be capable of forming three complexes with trivalent neodymium, Nd(EtTDPA), Nd(EtTDPA){sub 2}, and Nd(EtTDPA){sub 3}. Values from spectrophotometric and calorimetric titrations are within reasonable agreement with each other. The order of stability constants for each metal:ligand complex decreases in the order Et(m)TDPA > Et(p)TDPA > Et(o)TDPA. The obtained values are comparable to other di-amidic ligands obtained under similar system conditions and mirror previously obtained solvent extraction data for EtTDPA at low ionic strengths. (authors.

  9. Preparation and biological assessment of hydroxycinnamic acid amides of polyamines.

    PubMed

    Fixon-Owoo, Solomon; Levasseur, Frédéric; Williams, Keith; Sabado, Thomas N; Lowe, Mike; Klose, Markus; Joffre Mercier, A; Fields, Paul; Atkinson, Jeffrey

    2003-06-01

    Many plants contain hydroxycinnamic acid conjugates of polyamines that are remarkably similar in general structure to the acylated polyamines found in spider and wasp toxins. In an effort to determine whether these compounds might play a role in the chemical defense of plants against arthropod pests we synthesized a variety of analogues of the coumaric (4-hydroxycinnamic) acid conjugates of di-, tri-, and tetraamines using common protection and acylation strategies. N(1)- and N(8)-coumaroyl spermidine were tested in feeding trials with insect larvae including the European corn borer (Ostrinia nubilalis), the tobacco budworm (Heliothis verescens) and the oblique banded leaf roller (Choristoneura rosaceana). Antifeedant assays with the rice weevil Sitophilus oryzae were also performed. Neither the naturally occurring coumaric acid conjugates of polyamines nor their analogues showed notable toxicity towards insects, despite precautions to maintain these easily oxidized materials in the wet diet. However, more direct bioassays of these compounds on glutamate dependent neuroreceptors including the deep abdominal extensor muscles of crayfish, or mammalian NMDA, delta2, and AMPA receptors, clearly showed that these compounds were inhibitory. N(1)-Coumaoryl spermine, a dodecyl and a cyclohexyl analogue were especially active at NMDA NR1/NR2B receptors. The latter had an IC(50) of 300 microM in the crayfish. N(1)-Coumaroyl spermine had an IC(50) in the crayfish preparation of 70-300 microM and against the mammalian NR1/NR2B receptor of 38 nM. Structure-activity variations show similar trends of length and hydrophobicity as has been seen previously with analogues of spider toxins. We conclude from this work that while the coumaric acid polyamine conjugates are active when directly applied to neuroreceptors, they show no overt toxicity when ingested by insect larvae.

  10. Gas-Phase Amidation of Carboxylic Acids with Woodward's Reagent K Ions.

    PubMed

    Peng, Zhou; Pilo, Alice L; Luongo, Carl A; McLuckey, Scott A

    2015-10-01

    Gas-phase amidation of carboxylic acids in multiply-charged peptides is demonstrated via ion/ion reactions with Woodward's reagent K (wrk) in both positive and negative mode. Woodward's reagent K, N-ethyl-3-phenylisoxazolium-3'-sulfonate, is a commonly used reagent that activates carboxylates to form amide bonds with amines in solution. Here, we demonstrate that the analogous gas-phase chemistry occurs upon reaction of the wrk ions and doubly protonated (or doubly deprotonated) peptide ions containing the carboxylic acid functionality. The reaction involves the formation of the enol ester intermediate in the electrostatic complex. Upon collisional activation, the ethyl amine on the reagent is transferred to the activated carbonyl carbon on the peptide, resulting in the formation of an ethyl amide (addition of 27 Da to the peptide) with loss of a neutral ketene derivative. Further collision-induced dissociation (CID) of the products and comparison with solution-phase amidation product confirms the structure of the ethyl amide.

  11. Gas-Phase Amidation of Carboxylic Acids with Woodward's Reagent K Ions

    NASA Astrophysics Data System (ADS)

    Peng, Zhou; Pilo, Alice L.; Luongo, Carl A.; McLuckey, Scott A.

    2015-06-01

    Gas-phase amidation of carboxylic acids in multiply-charged peptides is demonstrated via ion/ion reactions with Woodward's reagent K (wrk) in both positive and negative mode. Woodward's reagent K, N-ethyl-3-phenylisoxazolium-3'-sulfonate, is a commonly used reagent that activates carboxylates to form amide bonds with amines in solution. Here, we demonstrate that the analogous gas-phase chemistry occurs upon reaction of the wrk ions and doubly protonated (or doubly deprotonated) peptide ions containing the carboxylic acid functionality. The reaction involves the formation of the enol ester intermediate in the electrostatic complex. Upon collisional activation, the ethyl amine on the reagent is transferred to the activated carbonyl carbon on the peptide, resulting in the formation of an ethyl amide (addition of 27 Da to the peptide) with loss of a neutral ketene derivative. Further collision-induced dissociation (CID) of the products and comparison with solution-phase amidation product confirms the structure of the ethyl amide.

  12. Fatty acid amide hydrolase inhibition for the symptomatic relief of Parkinson's disease.

    PubMed

    Celorrio, Marta; Fernández-Suárez, Diana; Rojo-Bustamante, Estefanía; Echeverry-Alzate, Víctor; Ramírez, María J; Hillard, Cecilia J; López-Moreno, José A; Maldonado, Rafael; Oyarzábal, Julen; Franco, Rafael; Aymerich, María S

    2016-10-01

    Elements of the endocannabinoid system are strongly expressed in the basal ganglia where they suffer profound rearrangements after dopamine depletion. Modulation of the levels of the endocannabinoid 2-arachidonoyl-glycerol by inhibiting monoacylglycerol lipase alters glial phenotypes and provides neuroprotection in a mouse model of Parkinson's disease. In this study, we assessed whether inhibiting fatty acid amide hydrolase could also provide beneficial effects on the time course of this disease. The fatty acid amide hydrolase inhibitor, URB597, was administered chronically to mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTPp) over 5weeks. URB597 (1mg/kg) prevented MPTPp induced motor impairment but it did not preserve the dopamine levels in the nigrostriatal pathway or regulate glial cell activation. The symptomatic relief of URB597 was confirmed in haloperidol-induced catalepsy assays, where its anti-cataleptic effects were both blocked by antagonists of the two cannabinoid receptors (CB1 and CB2), and abolished in animals deficient in these receptors. Other fatty acid amide hydrolase inhibitors, JNJ1661010 and TCF2, also had anti-cataleptic properties. Together, these results demonstrate an effect of fatty acid amide hydrolase inhibition on the motor symptoms of Parkinson's disease in two distinct experimental models that is mediated by cannabinoid receptors. PMID:27318096

  13. Fatty acid amide hydrolase inhibition for the symptomatic relief of Parkinson's disease.

    PubMed

    Celorrio, Marta; Fernández-Suárez, Diana; Rojo-Bustamante, Estefanía; Echeverry-Alzate, Víctor; Ramírez, María J; Hillard, Cecilia J; López-Moreno, José A; Maldonado, Rafael; Oyarzábal, Julen; Franco, Rafael; Aymerich, María S

    2016-10-01

    Elements of the endocannabinoid system are strongly expressed in the basal ganglia where they suffer profound rearrangements after dopamine depletion. Modulation of the levels of the endocannabinoid 2-arachidonoyl-glycerol by inhibiting monoacylglycerol lipase alters glial phenotypes and provides neuroprotection in a mouse model of Parkinson's disease. In this study, we assessed whether inhibiting fatty acid amide hydrolase could also provide beneficial effects on the time course of this disease. The fatty acid amide hydrolase inhibitor, URB597, was administered chronically to mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTPp) over 5weeks. URB597 (1mg/kg) prevented MPTPp induced motor impairment but it did not preserve the dopamine levels in the nigrostriatal pathway or regulate glial cell activation. The symptomatic relief of URB597 was confirmed in haloperidol-induced catalepsy assays, where its anti-cataleptic effects were both blocked by antagonists of the two cannabinoid receptors (CB1 and CB2), and abolished in animals deficient in these receptors. Other fatty acid amide hydrolase inhibitors, JNJ1661010 and TCF2, also had anti-cataleptic properties. Together, these results demonstrate an effect of fatty acid amide hydrolase inhibition on the motor symptoms of Parkinson's disease in two distinct experimental models that is mediated by cannabinoid receptors.

  14. Poly(ortho ester amides): Acid-labile Temperature-responsive Copolymers for Potential Biomedical Applications

    PubMed Central

    Tang, Rupei; Palumbo, R. Noelle; Ji, Weihang; Wang, Chun

    2009-01-01

    A new, convenient pathway is developed to synthesize highly hydrolytically labile poly(ortho ester amide) (POEA) copolymers that overcomes some of the major weaknesses of the traditional methods of synthesizing poly(ortho esters) and their derivatives. A diamine monomer containing a built-in, stabilized ortho ester group was synthesized and was used for polycondensation with diacid esters, giving rise to a series of POEA copolymers with unique stimuli-responsive properties. The POEA undergoes temperature-responsive, reversible sol-gel phase transition in water. Phase diagrams of the POEA/H2O mixture reveal the concentration-dependent existence of different phases, including hydrogel and opaque or clear solution. Such behavior may be attributed to the temperature-dependent hydrogen-bonding involving the amide groups in the POEA backbone and hydrophobic interactions between POEA chains, and it is tunable by selecting diacid monomers with different chemical structures. The kinetics of POEA mass loss in physiological aqueous buffers and release of a model macromolecular drug, fluorescently labeled dextran, are nearly zero-order, suggesting predominantly surface-restricted polymer erosion. The rates of polymer erosion and drug release are much faster at pH 5.0 than pH 7.4. No cytotoxicity was found for the polymer extracts and the polymer degradation products at concentrations as high as 1 mg/ml. The normal morphology of fibroblasts cultured directly in contact with POEA films was not altered. These novel acid-labile temperature-responsive POEA copolymers may be potentially useful for a wide range of biomedical applications such as minimal invasive delivery of controlled-release drug formulations that respond to biological temperature and acidic-pH environments in cells and tissues. PMID:19281150

  15. Synthesis and preliminary biological evaluations of (+)-isocampholenic acid-derived amides.

    PubMed

    Grošelj, Uroš; Golobič, Amalija; Knez, Damijan; Hrast, Martina; Gobec, Stanislav; Ričko, Sebastijan; Svete, Jurij

    2016-08-01

    The synthesis of two novel (+)-isocampholenic acid-derived amines has been realized starting from commercially available (1S)-(+)-10-camphorsulfonic acid. The novel amines as well as (+)-isocampholenic acid have been used as building blocks in the construction of a library of amides using various aliphatic, aromatic, and amino acid-derived coupling partners using BPC and CDI as activating agents. Amide derivatives have been assayed against several enzymes that hold potential for the development of new drugs to battle bacterial infections and Alzheimer's disease. Compounds 20c and 20e showed promising selective sub-micromolar inhibition of human butyrylcholinesterase [Formula: see text] ([Formula: see text] values [Formula: see text] and [Formula: see text], respectively). PMID:27017352

  16. Crystal structures and spectroscopic properties of ester amide and diamide of squaric acid with prolinamide

    NASA Astrophysics Data System (ADS)

    Kolev, Tsonko; Seidel, Rüdiger W.; Mayer-Figge, Heike; Spiteller, Michael; Sheldrick, William S.; Koleva, Bojidarka B.

    2009-04-01

    We report the synthesis, spectroscopic and structural elucidation of two prolinamide derivatives of squaric acid, i.e. prolinamide ester amide of squaric acid ethyl ester ( 1) and prolinamide diamide of squaric acid dihydrate ( 2). Both compounds crystallize in non-centrosymmetric space groups, monoclinic P2 1 ( 1) and orthorhombic P2 12 12 1 ( 2), respectively. For first time in the literature the crystal structure of homodiamide of amino acid amide of squaric acid is reported. The data for heterodiamides is also absent. Supramolecular zig-zag chains by hydrogen bonds of H 2N-C dbnd O⋯HNH (3.020 Å) and HNH⋯O dbnd C (Sq) (2.972 Å) types with the participation of amide and squaric acid (Sq) fragments, -C dbnd O-NH 2 and O dbnd C (Sq) are refined in ( 1). A helix supramolecular structure is formed in ( 2) by moderate intermolecular HNH⋯O dbnd C(NH 2) hydrogen bond with length of 2.947 Å. The two crystallographical non-equivalent water molecules stabilized the helix by interactions of types HOH⋯O dbnd C (Sq) (2.917 Å), HOH⋯O dbnd C(NH 2) (2.899 Å), H 2O⋯NH 2(C dbnd O) (2.972 Å), respectively. Optical and magnetic properties are investigated with a view to explain the correlation structure-properties of the newly synthesized molecules.

  17. Infrared spectroscopic study of the amidation reaction of aminophenyl modified Au surfaces and p-nitrobenzoic acid as model system.

    PubMed

    Zhang, Xin; Sun, Guoguang; Hinrichs, Karsten; Janietz, Silvia; Rappich, Joerg

    2010-10-21

    We have investigated the fundamental amidation reaction by a model system consisting of an electrochemically functionalised Au surface by aminophenyl and 4-nitrobenzoic acid activated by EEDQ. The development of the NO(2) related stretching vibrations with time reveals that the amidation process is very slow at Au surfaces and is completed after about 2 days.

  18. vir-Gene-inducing activities of hydroxycinnamic acid amides in Agrobacterium tumefaciens.

    PubMed

    Berthelot, K; Buret, D; Guerin, B; Delay, D; Negrel, J; Delmotte, F M

    1998-11-20

    Expression of Agrobacterium tumefaciens virulence genes and transformation of dicots by this organism are dependent upon host plant phenolic compounds. Several alkylsyringamides have recently been shown to be powerful inducers of these vir-genes. These synthetic amides, and especially ethylsyringamide, are much stronger inducers than syringic acid. In this work, four alkylamides derived from ferulic or sinapic acids were synthesized by a dicyclohexylcarbodiimide method and tested for their potential to induce vir-gene expression on A. tumefaciens strains harbouring virB::lacZ or virE::lacZ fusion plasmids. Their effectiveness was compared to that of ethylsyringamide and tyraminylferulamide, a naturally occurring amide in plants. Whatever the amine moiety of the amide (ethylamine, propylamine, tyramine or beta-alanine ethyl ester) conjugation of the acid functional group clearly diminished the toxicity to the bacteria of the respective acid at high concentration and thereby increased the vir-inducing potential. However, none of the inducers tested exhibited higher activity than acetosyringone, the reference compound for vir-gene induction, with the exception of ethylsyringamide at concentrations above 1mM. When tested on Agrobacterium tumefaciens strain A348(pSM243cd), ethylferulamide and ethylsinapamide were more efficient than the corresponding phenolic acids but only above 100 microM. PMID:11711062

  19. Synthesis, Properties and Applications of Biodegradable Polymers Derived from Diols and Dicarboxylic Acids: From Polyesters to Poly(ester amide)s

    PubMed Central

    Díaz, Angélica; Katsarava, Ramaz; Puiggalí, Jordi

    2014-01-01

    Poly(alkylene dicarboxylate)s constitute a family of biodegradable polymers with increasing interest for both commodity and speciality applications. Most of these polymers can be prepared from biobased diols and dicarboxylic acids such as 1,4-butanediol, succinic acid and carbohydrates. This review provides a current status report concerning synthesis, biodegradation and applications of a series of polymers that cover a wide range of properties, namely, materials from elastomeric to rigid characteristics that are suitable for applications such as hydrogels, soft tissue engineering, drug delivery systems and liquid crystals. Finally, the incorporation of aromatic units and α-amino acids is considered since stiffness of molecular chains and intermolecular interactions can be drastically changed. In fact, poly(ester amide)s derived from naturally occurring amino acids offer great possibilities as biodegradable materials for biomedical applications which are also extensively discussed. PMID:24776758

  20. A pro-nociceptive phenotype unmasked in mice lacking fatty-acid amide hydrolase

    PubMed Central

    Carey, Lawrence M; Slivicki, Richard A; Leishman, Emma; Cornett, Ben; Mackie, Ken; Bradshaw, Heather

    2016-01-01

    Fatty-acid amide hydrolase (FAAH) is the major enzyme responsible for degradation of anandamide, an endocannabinoid. Pharmacological inhibition or genetic deletion of FAAH (FAAH KO) produces antinociception in preclinical pain models that is largely attributed to anandamide-induced activation of cannabinoid receptors. However, FAAH metabolizes a wide range of structurally related, biologically active lipid signaling molecules whose functions remain largely unknown. Some of these endogenous lipids, including anandamide itself, may exert pro-nociceptive effects under certain conditions. In our study, FAAH KO mice exhibited a characteristic analgesic phenotype in the tail flick test and in both formalin and carrageenan models of inflammatory nociception. Nonetheless, intradermal injection of the transient receptor potential channel V1 (TRPV1) agonist capsaicin increased nocifensive behavior as well as mechanical and heat hypersensitivity in FAAH KO relative to wild-type mice. This pro-nociceptive phenotype was accompanied by increases in capsaicin-evoked Fos-like immunoreactive (FLI) cells in spinal dorsal horn regions implicated in nociceptive processing and was attenuated by CB1 (AM251) and TRPV1 (AMG9810) antagonists. When central sensitization was established, FAAH KO mice displayed elevated levels of anandamide, other fatty-acid amides, and endogenous TRPV1 agonists in both paw skin and lumbar spinal cord relative to wild-type mice. Capsaicin decreased spinal cord 2-AG levels and increased arachidonic acid and prostaglandin E2 levels in both spinal cord and paw skin irrespective of genotype. Our studies identify a previously unrecognized pro-nociceptive phenotype in FAAH KO mice that was unmasked by capsaicin challenge. The heightened nociceptive response was mediated by CB1 and TRPV1 receptors and accompanied by enhanced spinal neuronal activation. Moreover, genetic deletion of FAAH has a profound impact on the peripheral and central lipidome. Thus, genetic

  1. /sup 17/O NMR spectroscopy: torsion angle relationships in aryl carboxylic esters, acids, and amides

    SciTech Connect

    Baumstark, A.L.; Balakrishnan, P.; Dotrong, M.; McCloskey, C.J.; Oakley, M.G.; Boykin, D.W.

    1987-02-18

    /sup 1/ /sup 7/O NMR spectroscopic data (natural abundance in acetonitrile at 75/sup 0/C) were obtained for the following series of electronically similar, sterically hindered compounds: aromatic methyl esters, aromatic carboxylic acids, and aromatic amides. Torsional angles were calculated by the molecular mechanics (MM2) method. Linear regression analysis of the estimated torsion angles and the /sup 17/O chemical shift data for each series yielded the following results (series, slope delta/degree, correlation coefficient): esters (C=O), 0.70, 0.997; esters (-0-), 0.43, 0.992; acids (-CO/sub 2/H), 0.56, 0.994; amides (C=O), 0.84, 0.942; N,N-dimethylamides (C=O), 0.6, 0.991. The results are discussed in terms of minimization of repulsive van der Waals interactions by rotation of the functional group out of the plane of the aromatic ring.

  2. Antimycobacterial activity generated by the amide coupling of (-)-fenchone derived aminoalcohol with cinnamic acids and analogues.

    PubMed

    Slavchev, Ivaylo; Dobrikov, Georgi M; Valcheva, Violeta; Ugrinova, Iva; Pasheva, Evdokia; Dimitrov, Vladimir

    2014-11-01

    Aminoethyl substituted 2-endo-fenchol prepared from (-)-fenchone was used as scaffold for the synthesis of series of 31 amide structures by N-acylation applying cinnamic acids and analogues. The evaluation of their in vitro activity against Mycobacterium tuberculosis H37Rv showed for some of them promising activity-up to 0.2 μg/ml, combined with relatively low cytotoxicity of the selected active compounds.

  3. Primary fatty acid amide metabolism: conversion of fatty acids and an ethanolamine in N18TG2 and SCP cells.

    PubMed

    Farrell, Emma K; Chen, Yuden; Barazanji, Muna; Jeffries, Kristen A; Cameroamortegui, Felipe; Merkler, David J

    2012-02-01

    Primary fatty acid amides (PFAM) are important signaling molecules in the mammalian nervous system, binding to many drug receptors and demonstrating control over sleep, locomotion, angiogenesis, and many other processes. Oleamide is the best-studied of the primary fatty acid amides, whereas the other known PFAMs are significantly less studied. Herein, quantitative assays were used to examine the endogenous amounts of a panel of PFAMs, as well as the amounts produced after incubation of mouse neuroblastoma N(18)TG(2) and sheep choroid plexus (SCP) cells with the corresponding fatty acids or N-tridecanoylethanolamine. Although five endogenous primary amides were discovered in the N(18)TG(2) and SCP cells, a different pattern of relative amounts were found between the two cell lines. Higher amounts of primary amides were found in SCP cells, and the conversion of N-tridecanoylethanolamine to tridecanamide was observed in the two cell lines. The data reported here show that the N(18)TG(2) and SCP cells are excellent model systems for the study of PFAM metabolism. Furthermore, the data support a role for the N-acylethanolamines as precursors for the PFAMs and provide valuable new kinetic results useful in modeling the metabolic flux through the pathways for PFAM biosynthesis and degradation.

  4. MATE Transporter-Dependent Export of Hydroxycinnamic Acid Amides[OPEN

    PubMed Central

    Eschen-Lippold, Lennart; Gorzolka, Karin; Matern, Andreas; Marillonnet, Sylvestre; Böttcher, Christoph; Rosahl, Sabine

    2016-01-01

    The ability of Arabidopsis thaliana to successfully prevent colonization by Phytophthora infestans, the causal agent of late blight disease of potato (Solanum tuberosum), depends on multilayered defense responses. To address the role of surface-localized secondary metabolites for entry control, droplets of a P. infestans zoospore suspension, incubated on Arabidopsis leaves, were subjected to untargeted metabolite profiling. The hydroxycinnamic acid amide coumaroylagmatine was among the metabolites secreted into the inoculum. In vitro assays revealed an inhibitory activity of coumaroylagmatine on P. infestans spore germination. Mutant analyses suggested a requirement of the p-coumaroyl-CoA:agmatine N4-p-coumaroyl transferase ACT for the biosynthesis and of the MATE transporter DTX18 for the extracellular accumulation of coumaroylagmatine. The host plant potato is not able to efficiently secrete coumaroylagmatine. This inability is overcome in transgenic potato plants expressing the two Arabidopsis genes ACT and DTX18. These plants secrete agmatine and putrescine conjugates to high levels, indicating that DTX18 is a hydroxycinnamic acid amide transporter with a distinct specificity. The export of hydroxycinnamic acid amides correlates with a decreased ability of P. infestans spores to germinate, suggesting a contribution of secreted antimicrobial compounds to pathogen defense at the leaf surface. PMID:26744218

  5. Synthesis, biological activity, and bioavailability of moschamine, a safflomide-type phenylpropenoic acid amide found in Centaurea cyanus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Moschamine is a safflomide-type phenylpropenoic acid amide originally isolated from Centaurea cyanus. This paper describes the synthesis, detection of serotoninergic and COX inhibitory activities, and bioavailability of moschamine. Moschamine was chemically synthesized and identified using NMR spect...

  6. Sulfonated reduced graphene oxide as a highly efficient catalyst for direct amidation of carboxylic acids with amines using ultrasonic irradiation.

    PubMed

    Mirza-Aghayan, Maryam; Tavana, Mahdieh Molaee; Boukherroub, Rabah

    2016-03-01

    Sulfonated reduced graphene oxide nanosheets (rGO-SO3H) were prepared by grafting sulfonic acid-containing aryl radicals onto chemically reduced graphene oxide (rGO) under sonochemical conditions. rGO-SO3H catalyst was characterized by Fourier-transform infrared (FT-IR) spectroscopy, Raman spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and X-ray photoelectron spectroscopy (XPS). rGO-SO3H catalyst was successfully applied as a reusable solid acid catalyst for the direct amidation of carboxylic acids with amines into the corresponding amides under ultrasonic irradiation. The direct sonochemical amidation of carboxylic acid takes place under mild conditions affording in good to high yields (56-95%) the corresponding amides in short reaction times.

  7. Design, synthesis, and evaluation of caffeic acid amides as synergists to sensitize fluconazole-resistant Candida albicans to fluconazole.

    PubMed

    Dai, Li; Zang, Chengxu; Tian, Shujuan; Liu, Wei; Tan, Shanlun; Cai, Zhan; Ni, Tingjunhong; An, Maomao; Li, Ran; Gao, Yue; Zhang, Dazhi; Jiang, Yuanying

    2015-01-01

    A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 34c, at a concentration of 1.0 μg/ml, decreased the MIC₈₀ of fluconazole from 128.0 μg/ml to 1.0-0.5 μg/ml against the fluconazole-resistant C. albicans. This result suggests that the caffeic acid amides, as synergists, can sensitize drug-resistant fungi to fluconazole. The SAR study indicated that the dihydroxyl groups and the amido groups linking to phenyl or heterocyclic rings are the important pharmacophores of the caffeic acid amides.

  8. Attenuation of Cystitis and Pain Sensation in Mice Lacking Fatty Acid Amide Hydrolase

    PubMed Central

    Wang, Zun-Yi; Wang, Peiqing; Hillard, Cecilia J.; Bjorling, Dale E.

    2015-01-01

    Endocannabinoids, such as N-arachidonylethanolamine (AEA, also called anandamide), exert potent analgesic and anti-inflammatory effects. Fatty acid amide hydrolase (FAAH) is primarily responsible for degradation of AEA, and deletion of FAAH increases AEA content in various tissues. Since FAAH has been shown to be present in the bladder of various species, we compared bladder function, severity of experimental cystitis, and cystitis-associated referred hyperalgesia in male wild type (WT) and FAAH knock-out (KO) mice. Basal concentrations of AEA were greater, and the severity of cyclophosphamide (CYP)-induced cystitis was reduced in bladders from FAAH KO compared to WT mice. Cystitis-associated increased peripheral sensitivity to mechanical stimuli and enhanced bladder activity (as reflected by increased voiding frequency) were attenuated in FAAH KO compared to WT mice. Further, abundances of mRNA for several pro-inflammatory compounds were increased in bladder mucosa after CYP treatment of WT mice, and this increase was inhibited in FAAH KO mice. These data indicate that endogenous substrates of FAAH, including the cannabinoid AEA, play an inhibitory role in bladder inflammation and subsequent changes in pain perception. Therefore, FAAH could be a therapeutic target to treat clinical symptoms of painful inflammatory bladder diseases. PMID:25374388

  9. Complexation of amidated pectin with poly(itaconic acid) as a polycarboxylic polymer model compound.

    PubMed

    Nesic, Aleksandra R; Trifunovic, Snezana S; Grujic, Aleksandar S; Velickovic, Sava J; Antonovic, Dusan G

    2011-11-01

    Complexes based on amidated pectin (AP) and poly(itaconic acid) (PIA) were prepared by casting films from solutions of AP and PIA in different ratios with the pectin amount ranging from 10% to 90% by mass. The complexes were investigated by elemental analysis, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and thermogravimetry (TG). In all investigated ratios of AP/PIA glassy transparent films with a uniform structure were obtained. The results of elemental analysis confirmed the composition of the complexes, and FTIR spectroscopy has shown carboxylic and amide peak shifting, indicating complex formation between AP and PIA. Comparison of thermograms of AP/PIA films with different ratios of AP indicated that the increase of the amount of AP increases the thermal stability of the films by retarding the onset of the main degradation processes. PMID:21943549

  10. Probing acid-amide intermolecular hydrogen bonding by NMR spectroscopy and DFT calculations

    NASA Astrophysics Data System (ADS)

    Chaudhari, Sachin Rama; Suryaprakash, N.

    2012-05-01

    Benzene carboxylic acids and benzamide act as their self-complement in molecular recognition to form inter-molecular hydrogen bonded dimers between amide and carboxylic acid groups, which have been investigated by 1H, 13C and 15N NMR spectroscopy. Extensive NMR studies using diffusion ordered spectroscopy (DOSY), variable temperature 1D, 2D NMR, established the formation of heterodimers of benzamide with benzoic acid, salicylic acid and phenyl acetic acid in deuterated chloroform solution. Association constants for the complex formation in the solution state have been determined. The results are ascertained by X-ray diffraction in the solid state. Intermolecular interactions in solution and in solid state were found to be similar. The structural parameters obtained by X-ray diffraction studies are compared with those obtained by DFT calculations.

  11. Temperature dependence of amino acid side chain IR absorptions in the amide I' region.

    PubMed

    Anderson, Benjamin A; Literati, Alex; Ball, Borden; Kubelka, Jan

    2014-05-01

    Amide I' IR spectra are widely used for studies of structural changes in peptides and proteins as a function of temperature. Temperature dependent absorptions of amino acid side-chains that overlap the amide I' may significantly complicate the structural analyses. While the side-chain IR spectra have been investigated previously, thus far their dependence on temperature has not been reported. Here we present the study of the changes in the IR spectra with temperature for side-chain groups of aspartate, glutamate, asparagine, glutamine, arginine, and tyrosine in the amide I' region (in D2O). Band fitting analysis was employed to extract the temperature dependence of the individual spectral parameters, such as peak frequency, integrated intensity, band width, and shape. As expected, the side-chain IR bands exhibit significant changes with temperature. The majority of the spectral parameters, particularly the frequency and intensity, show linear dependence on temperature, but the direction and magnitude vary depending on the particular side-chain group. The exception is arginine, which exhibits a distinctly nonlinear frequency shift with temperature for its asymmetric CN3H5(+) bending signal, although a linear fit can account for this change to within ~1/3 cm(-1). The applicability of the determined spectral parameters for estimations of temperature-dependent side-chain absorptions in peptides and proteins are discussed.

  12. Hydrogen-deuterium exchange of aromatic amines and amides using deuterated trifluoroacetic acid

    PubMed Central

    Giles, Richard; Lee, Amy; Jung, Erica; Kang, Aaron; Jung, Kyung Woon

    2014-01-01

    The H-D exchange of aromatic amines and amides, including pharmaceutically relevant compounds such as acetaminophen and diclofenac, was investigated using CF3COOD as both the sole reaction solvent and source of deuterium label. The described method is amenable to efficient deuterium incorporation for a wide variety of substrates possessing both electron-donating and electron-withdrawing substituents. Best results were seen with less basic anilines and highly activated acetanilides, reflecting the likelihood of different mechanistic pathways. PMID:25641994

  13. Synthesis, Anti-HCV, Antioxidant and Reduction of Intracellular Reactive Oxygen Species Generation of a Chlorogenic Acid Analogue with an Amide Bond Replacing the Ester Bond.

    PubMed

    Wang, Ling-Na; Wang, Wei; Hattori, Masao; Daneshtalab, Mohsen; Ma, Chao-Mei

    2016-06-08

    Chlorogenic acid is a well known natural product with important bioactivities. It contains an ester bond formed between the COOH of caffeic acid and the 3-OH of quinic acid. We synthesized a chlorogenic acid analogue, 3α-caffeoylquinic acid amide, using caffeic and quinic acids as starting materials. The caffeoylquinc acid amide was found to be much more stable than chlorogenic acid and showed anti-Hepatitis C virus (anti-HCV) activity with a potency similar to chlorogenic acid. The caffeoylquinc acid amide potently protected HepG2 cells against oxidative stress induced by tert-butyl hydroperoxide.

  14. Synthesis, Anti-HCV, Antioxidant and Reduction of Intracellular Reactive Oxygen Species Generation of a Chlorogenic Acid Analogue with an Amide Bond Replacing the Ester Bond.

    PubMed

    Wang, Ling-Na; Wang, Wei; Hattori, Masao; Daneshtalab, Mohsen; Ma, Chao-Mei

    2016-01-01

    Chlorogenic acid is a well known natural product with important bioactivities. It contains an ester bond formed between the COOH of caffeic acid and the 3-OH of quinic acid. We synthesized a chlorogenic acid analogue, 3α-caffeoylquinic acid amide, using caffeic and quinic acids as starting materials. The caffeoylquinc acid amide was found to be much more stable than chlorogenic acid and showed anti-Hepatitis C virus (anti-HCV) activity with a potency similar to chlorogenic acid. The caffeoylquinc acid amide potently protected HepG2 cells against oxidative stress induced by tert-butyl hydroperoxide. PMID:27338318

  15. Acute Neurologic Disorder from an Inhibitor of Fatty Acid Amide Hydrolase.

    PubMed

    Kerbrat, Anne; Ferré, Jean-Christophe; Fillatre, Pierre; Ronzière, Thomas; Vannier, Stéphane; Carsin-Nicol, Béatrice; Lavoué, Sylvain; Vérin, Marc; Gauvrit, Jean-Yves; Le Tulzo, Yves; Edan, Gilles

    2016-11-01

    Background A decrease in fatty acid amide hydrolase (FAAH) activity increases the levels of endogenous analogues of cannabinoids, or endocannabinoids. FAAH inhibitors have shown analgesic and antiinflammatory activity in animal models, and some have been tested in phase 1 and 2 studies. In a phase 1 study, BIA 10-2474, an orally administered reversible FAAH inhibitor, was given to healthy volunteers to assess safety. Methods Single doses (0.25 to 100 mg) and repeated oral doses (2.5 to 20 mg for 10 days) of BIA 10-2474 had been administered to 84 healthy volunteers in sequential cohorts; no severe adverse events had been reported. Another cohort of participants was then assigned to placebo (2 participants) or 50 mg of BIA 10-2474 per day (6 participants). This report focuses on neurologic adverse events in participants in this final cohort. A total of 4 of the 6 participants who received active treatment consented to have their clinical and radiologic data included in this report. Results An acute and rapidly progressive neurologic syndrome developed in three of the four participants starting on the fifth day of drug administration. The main clinical features were headache, a cerebellar syndrome, memory impairment, and altered consciousness. Magnetic resonance imaging showed bilateral and symmetric cerebral lesions, including microhemorrhages and hyperintensities on fluid-attenuated inversion recovery and diffusion-weighted imaging sequences predominantly involving the pons and hippocampi. One patient became brain dead; the condition of two patients subsequently improved, but one patient had residual memory impairment, and the other patient had a residual cerebellar syndrome. One patient remained asymptomatic. Conclusions An unanticipated severe neurologic disorder occurred after ingestion of BIA 10-2474 at the highest dose level used in a phase 1 trial. The underlying mechanism of this toxic cerebral syndrome remains unknown.

  16. Bipiperidinyl carboxylic acid amides as potent, selective, and functionally active CCR4 antagonists.

    PubMed

    Kuhn, Cyrille F; Bazin, Marc; Philippe, Laurence; Zhang, Jiansu; Tylaska, Laurie; Miret, Juan; Bauer, Paul H

    2007-09-01

    A cell-based assay for the chemokine G-protein-coupled receptor CCR4 was developed, and used to screen a small-molecule compound collection in a multiplex format. A series of bipiperidinyl carboxylic acid amides amenable to parallel chemistry were derived that were potent and selective antagonists of CCR4. One prototype compound was shown to be active in a functional model of chemotaxis, making it a useful chemical tool to explore the role of CCR4 in asthma, allergy, diabetes, and cancer.

  17. Fatty acid amide supplementation decreases impulsivity in young adult heavy drinkers.

    PubMed

    van Kooten, Maria J; Veldhuizen, Maria G; de Araujo, Ivan E; O'Malley, Stephanie S; Small, Dana M

    2016-03-01

    Compromised dopamine signaling in the striatum has been associated with the expression of impulsive behaviors in addiction, obesity and alcoholism. In rodents, intragastric infusion of the fatty acid amide oleoylethanolamide increases striatal extracellular dopamine levels via vagal afferent signaling. Here we tested whether supplementation with PhosphoLean™, a dietary supplement that contains the precursor of the fatty acid amide oleoylethanolamide (N-oleyl-phosphatidylethanolamine), would reduce impulsive responding and alcohol use in heavy drinking young adults. Twenty-two individuals were assigned to a three-week supplementation regimen with PhosphoLean™ or placebo. Impulsivity was assessed with self-report questionnaires and behavioral tasks pre- and post-supplementation. Although self-report measures of impulsivity did not change, supplementation with PhosphoLean™, but not placebo, significantly reduced false alarm rate on a Go/No-Go task. In addition, an association was found between improved sensitivity on the Go/No-Go task and reduced alcohol intake. These findings provide preliminary evidence that promoting fatty acid derived gut-brain dopamine communication may have therapeutic potential for reducing impulsivity in heavy drinkers.

  18. Electrostatic interaction of pi-acidic amides with hydrogen-bond acceptors.

    PubMed

    Li, Yi; Snyder, Lawrence B; Langley, David R

    2003-10-01

    Interactions between N-methylacetamide (NMA) and N-methylated derivatives of uracil, isocyanurate and barbituric acid have been studied using ab initio methods at the local MP2/6-31G** level of theory. The results were compared to similar interactions between the oxygen atom of NMA and the pi-clouds of perfluorobenzene, quinone and trimethyltriazine. The pi-acidic amides of isocyanurate and barbituric acid were found to interact with a hydrogen bond acceptor primarily through electrostatic attractions. These groups may be used as alternatives of a hydrogen bond donor to complement a hydrogen bond acceptor or an anion in molecular recognition and drug design. Examples of such interactions were identified through a search of the CSD database.

  19. Synthesis and biological evaluation of piperic acid amides as free radical scavengers and α-glucosidase inhibitors.

    PubMed

    Takao, Koichi; Miyashiro, Takaki; Sugita, Yoshiaki

    2015-01-01

    A series of piperic acid amides (4-24, 29, 30) were synthesized and their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and α-glucosidase inhibitory activities were evaluated. Among the synthesized compounds, the amides 11, 13 and 15, which contain o-methoxyphenol, catechol or 5-hydroxyindole moieties, showed potent DPPH free radical scavenging activity (11: EC50 140 µM; 13: EC50 28 µM; 15: EC50 20 µM). The amides 10, 18 and 23 showed higher inhibitory activity of α-glucosidase (10: IC50 21 µM; 18: IC50 21 µM; 23: IC50 12 µM). These data suggest that the hydrophobicity of the conjugated amines is an important determinant of α-glucosidase inhibitory activity. In addition, the amides 13 and 15 showed both potent DPPH free radical scavenging activity and α-glucosidase inhibitory activity (13: IC50 46 µM; 15: IC50 46 µM). This is the first report identifying the DPPH free radical scavenging and α-glucosidase inhibitory activities of piperic acid amides and suggests that these amides may serve as lead compounds for the development of novel α-glucosidase inhibitors with antioxidant activity.

  20. Synthesis and biological evaluation of piperic acid amides as free radical scavengers and α-glucosidase inhibitors.

    PubMed

    Takao, Koichi; Miyashiro, Takaki; Sugita, Yoshiaki

    2015-01-01

    A series of piperic acid amides (4-24, 29, 30) were synthesized and their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and α-glucosidase inhibitory activities were evaluated. Among the synthesized compounds, the amides 11, 13 and 15, which contain o-methoxyphenol, catechol or 5-hydroxyindole moieties, showed potent DPPH free radical scavenging activity (11: EC50 140 µM; 13: EC50 28 µM; 15: EC50 20 µM). The amides 10, 18 and 23 showed higher inhibitory activity of α-glucosidase (10: IC50 21 µM; 18: IC50 21 µM; 23: IC50 12 µM). These data suggest that the hydrophobicity of the conjugated amines is an important determinant of α-glucosidase inhibitory activity. In addition, the amides 13 and 15 showed both potent DPPH free radical scavenging activity and α-glucosidase inhibitory activity (13: IC50 46 µM; 15: IC50 46 µM). This is the first report identifying the DPPH free radical scavenging and α-glucosidase inhibitory activities of piperic acid amides and suggests that these amides may serve as lead compounds for the development of novel α-glucosidase inhibitors with antioxidant activity. PMID:25948326

  1. Cinnamic acid amides from Tribulus terrestris displaying uncompetitive α-glucosidase inhibition.

    PubMed

    Song, Yeong Hun; Kim, Dae Wook; Curtis-Long, Marcus J; Park, Chanin; Son, Minky; Kim, Jeong Yoon; Yuk, Heung Joo; Lee, Keun Woo; Park, Ki Hun

    2016-05-23

    The α-glucosidase inhibitory potential of Tribulus terrestris extracts has been reported but as yet the active ingredients are unknown. This study attempted to isolate the responsible metabolites and elucidate their inhibition mechanism of α-glucosidase. By fractionating T. terristris extracts, three cinnamic acid amide derivatives (1-3) were ascertained to be active components against α-glucosidase. The lead structure, N-trans-coumaroyltyramine 1, showed significant inhibition of α-glucosidase (IC50 = 0.42 μM). Moreover, all active compounds displayed uncompetitive inhibition mechanisms that have rarely been reported for α-glucosidase inhibitors. This kinetic behavior was fully demonstrated by showing a decrease of both Km and Vmax, and Kik/Kiv ratio ranging between 1.029 and 1.053. We progressed to study how chemical modifications to the lead structure 1 may impact inhibition. An α, β-unsaturation carbonyl group and hydroxyl group in A-ring of cinnamic acid amide emerged to be critical functionalities for α-glucosidase inhibition. The molecular modeling study revealed that the inhibitory activities are tightly related to π-π interaction as well as hydrogen bond interaction between enzyme and inhibitors.

  2. An Investigation of Solid-State Amidization and Imidization Reactions in Vapor Deposited Poly (amic acid)

    SciTech Connect

    Anthamatten, M; Letts, S A; Day, K; Cook, R C; Gies, A P; Hamilton, T P; Nonidez, W K

    2004-06-28

    The condensation polymerization reaction of 4,4'-oxydianiline (ODA) with pyromellitic dianhydride (PMDA) to form poly(amic acid) and the subsequent imidization reaction to form polyimide were investigated for films prepared using vapor deposition polymerization techniques. Fourier-transform infrared spectroscopy (FT-IR), thermal analysis, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) of films at different temperatures indicate that additional solid-state polymerization occurs prior to imidization reactions. Experiments reveal that, upon vapor deposition, poly(amic acid) oligomers form that have a number-average molecular weight of about 1500 Daltons. Between 100 - 130 C these chains undergo additional condensation reaction to form slightly higher molecular weight oligomers. Calorimetry measurements show that this reaction is exothermic ({Delta}H {approx} -30 J/g) with an activation energy of about 120 kJ/mol. Experimental reaction enthalpies are compared to results from ab initio molecular modeling calculations to estimate the number of amide groups formed. At higher temperatures (150 - 300 C) imidization of amide linkages occurs as an endothermic reaction ({Delta}H {approx} +120 J/g) with an activation energy of about 130 kJ/mol. Solid-state kinetics were found to depend on reaction conversion as well as the processing conditions used to deposit films.

  3. Modular Synthesis of Arylacetic Acid Esters, Thioesters, and Amides from Aryl Ethers via Rh(II)-Catalyzed Diazo Arylation.

    PubMed

    Best, Daniel; Jean, Mickaël; van de Weghe, Pierre

    2016-09-01

    One-pot formation of arylacetic acid esters, thioesters, and amides via Rh(II)-catalyzed arylation of a Meldrum's acid-derived diazo reagent with electron-rich arenes is described. The methodology was used to efficiently synthesize an anticancer compound. PMID:27465907

  4. 40 CFR 721.10410 - Polyether ester acid compound with a polyamine amide (generic) (P-05-714).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polyether ester acid compound with a polyamine amide (generic) (P-05-714). 721.10410 Section 721.10410 Protection of Environment ENVIRONMENTAL... Significant New Uses for Specific Chemical Substances § 721.10410 Polyether ester acid compound with...

  5. Enzymatically and reductively degradable α-amino acid-based poly(ester amide)s: synthesis, cell compatibility, and intracellular anticancer drug delivery.

    PubMed

    Sun, Huanli; Cheng, Ru; Deng, Chao; Meng, Fenghua; Dias, Aylvin A; Hendriks, Marc; Feijen, Jan; Zhong, Zhiyuan

    2015-02-01

    A novel and versatile family of enzymatically and reductively degradable α-amino acid-based poly(ester amide)s (SS-PEAs) were developed from solution polycondensation of disulfide-containing di-p-toluenesulfonic acid salts of bis-l-phenylalanine diesters (SS-Phe-2TsOH) with di-p-nitrophenyl adipate (NA) in N,N-dimethylformamide (DMF). SS-PEAs with Mn ranging from 16.6 to 23.6 kg/mol were obtained, depending on NA/SS-Phe-2TsOH molar ratios. The chemical structures of SS-PEAs were confirmed by (1)H NMR and FTIR spectra. Thermal analyses showed that the obtained SS-PEAs were amorphous with a glass transition temperature (Tg) in the range of 35.2-39.5 °C. The in vitro degradation studies of SS-PEA films revealed that SS-PEAs underwent surface erosion in the presence of 0.1 mg/mL α-chymotrypsin and bulk degradation under a reductive environment containing 10 mM dithiothreitol (DTT). The preliminary cell culture studies displayed that SS-PEA films could well support adhesion and proliferation of L929 fibroblast cells, indicating that SS-PEAs have excellent cell compatibility. The nanoparticles prepared from SS-PEA with PVA as a surfactant had an average size of 167 nm in phosphate buffer (PB, 10 mM, pH 7.4). SS-PEA nanoparticles while stable under physiological environment undergo rapid disintegration under an enzymatic or reductive condition. The in vitro drug release studies showed that DOX release was accelerated in the presence of 0.1 mg/mL α-chymotrypsin or 10 mM DTT. Confocal microscopy observation displayed that SS-PEA nanoparticles effectively transported DOX into both drug-sensitive and -resistant MCF-7 cells. MTT assays revealed that DOX-loaded SS-PEA nanoparticles had a high antitumor activity approaching that of free DOX in drug-sensitive MCF-7 cells, while more than 10 times higher than free DOX in drug-resistant MCF-7/ADR cells. These enzymatically and reductively degradable α-amino acid-based poly(ester amide)s have provided an appealing platform for

  6. Metal cation dependence of interactions with amino acids: bond dissociation energies of Rb(+) and Cs(+) to the acidic amino acids and their amide derivatives.

    PubMed

    Armentrout, P B; Yang, Bo; Rodgers, M T

    2014-04-24

    Metal cation-amino acid interactions are key components controlling the secondary structure and biological function of proteins, enzymes, and macromolecular complexes comprising these species. Determination of pairwise interactions of alkali metal cations with amino acids provides a thermodynamic vocabulary that begins to quantify these fundamental processes. In the present work, we expand a systematic study of such interactions by examining rubidium and cesium cations binding with the acidic amino acids (AA), aspartic acid (Asp) and glutamic acid (Glu), and their amide derivatives, asparagine (Asn) and glutamine (Gln). These eight complexes are formed using electrospray ionization and their bond dissociation energies (BDEs) are determined experimentally using threshold collision-induced dissociation with xenon in a guided ion beam tandem mass spectrometer. Analyses of the energy-dependent cross sections include consideration of unimolecular decay rates, internal energy of the reactant ions, and multiple ion-neutral collisions. Quantum chemical calculations are conducted at the B3LYP, MP2(full), and M06 levels of theory using def2-TZVPPD basis sets, with results showing reasonable agreement with experiment. At 0 and 298 K, most levels of theory predict that the ground-state conformers for M(+)(Asp) and M(+)(Asn) involve tridentate binding of the metal cation to the backbone carbonyl, amino, and side-chain carbonyl groups, although tridentate binding to the carboxylic acid group and side-chain carbonyl is competitive for M(+)(Asn). For the two longer side-chain amino acids, Glu and Gln, multiple structures are competitive. A comparison of these results to those for the smaller alkali cations, Na(+) and K(+), provides insight into the trends in binding energies associated with the molecular polarizability and dipole moment of the side chain. For all four metal cations, the BDEs are inversely correlated with the size of the metal cation and follow the order Asp < Glu

  7. Accelerated Amidization of Branched Poly(ethylenimine)/Poly(acrylic acid) Multilayer Films by Microwave Heating.

    PubMed

    Lin, Kehua; Gu, Yuanqing; Zhang, Huan; Qiang, Zhe; Vogt, Bryan D; Zacharia, Nicole S

    2016-09-13

    Chemical cross-linking of layer-by-layer assembled films promotes mechanical stability and robustness in a wide variety of environments, which can be a challenge for polyelectrolyte multilayers in saline environments or for multilayers made from weak polyelectrolytes in environments with extreme pHs. Heating branched poly(ethylenimine)/poly(acrylic acid) (BPEI/PAA) multilayers at sufficiently high temperatures drives amidization and dehydration to covalently cross-link the film, but this reaction is rather slow, typically requiring heating for hours for appreciable cross-linking to occur. Here, a more than one order of magnitude increase in the amidization kinetics is realized through microwave heating of BPEI/PAA multilayers on indium tin oxide (ITO)/glass substrates. The cross-linking reaction is tracked using infrared spectroscopic ellipsometry to monitor the development of the cross-linking products. For thick films (∼1500 nm), gradients in cross-link density can be readily identified by infrared ellipsometry. Such gradients in cross-link density are driven by the temperature gradient developed by the localized heating of ITO by microwaves. This significant acceleration of reactions using microwaves to generate a well-defined cross-link network as well as being a simple method for developing graded materials should open new applications for these polymer films and coatings. PMID:27548626

  8. A Computational Study of Cytotoxicity of Substituted Amides of Pyrazine- 2-carboxylic acids Using QSAR and DFT Based Molecular Surface Electrostatic Potential

    PubMed Central

    Hosseini, Sharieh; Monajjemi, Majid; Rajaeian, Elahe; Haghgu, Mohammad; Salari, Aliakbar; Gholami, Mohammad Reza

    2013-01-01

    Pyrazine derivatives are important class of compounds with diverse biological and cytotoxic activities and clinical applications. In this study, B3 p 86 / 6 – 31 + + G * was used to compute and map the molecular surface electrostatic potentials of a group of substituted amides of pyrazine-2-carboxylic acids to identify common features related to their subsequent cytotoxicities. Several statistical properties including potentials extrema (Vs ,min,Vs ,max), the average of positive electrostatic potential on the surface (Vs+), the average of V(r) over the surface (Vs) and the Lowest Unoccupied Molecular Orbital (LUMO) and system cytotoxicities were computed. Statistically, the most significant correlation is a five -parameter equation with correlation coefficient, R² values of 0.922 and R²adj = 0.879. The obtained models allowed us to reveal cytotoxic activity of substituted amides of Pyrazine2- carboxcylic acid. PMID:24523754

  9. Efficient Gene Silencing by Self-Assembled Complexes of siRNA and Symmetrical Fatty Acid Amides of Spermine

    PubMed Central

    Metwally, Abdelkader A.; Pourzand, Charareh; Blagbrough, Ian S.

    2011-01-01

    Gene silencing by siRNA (synthetic dsRNA of 21-25 nucleotides) is a well established biological tool in gene expression studies and has a promising therapeutic potential for difficult-to-treat diseases. Five fatty acids of various chain length and oxidation state (C12:0, C18:0, C18:1, C18:2, C22:1) were conjugated to the naturally occurring polyamine, spermine, and evaluated for siRNA delivery and gene knock-down. siRNA delivery could not be related directly to gene silencing efficiency as N4,N9-dierucoyl spermine resulted in higher siRNA delivery compared to N4,N9-dioleoyl spermine. GFP silencing in HeLa cells showed that the unsaturated fatty acid amides are more efficient than saturated fatty acid amides, with N4,N9-dioleoyl spermine resulting in the most efficient gene silencing in the presence of serum. The alamarBlue cell viability assay showed that fatty acid amides of spermine have good viability (75%–85% compared to control) except N4,N9-dilauroyl spermine which resulted in low cell viability. These results prove that unsaturated fatty acid amides of spermine are efficient, non-toxic, non-viral vectors for siRNA mediated gene silencing. PMID:24310492

  10. A spectrophotometric assay for fatty acid amide hydrolase suitable for high-throughput screening.

    PubMed

    De Bank, Paul A; Kendall, David A; Alexander, Stephen P H

    2005-04-15

    Signalling via the endocannabinoids anandamide and 2-arachidonylglycerol appears to be terminated largely through the action of the enzyme fatty acid amide hydrolase (FAAH). In this report, we describe a simple spectrophotometric assay to detect FAAH activity in vitro using the ability of the enzyme to hydrolyze oleamide and measuring the resultant production of ammonia with a NADH/NAD+-coupled enzyme reaction. This dual-enzyme assay was used to determine Km and Vmax values of 104 microM and 5.7 nmol/min/mgprotein, respectively, for rat liver FAAH-catalyzed oleamide hydrolysis. Inhibitor potency was determined with the resultant rank order of methyl arachidonyl fluorophosphonate>phenylmethylsulphonyl fluoride>anandamide. This assay system was also adapted for use in microtiter plates and its ability to detect a known inhibitor of FAAH demonstrated, highlighting its potential for use in high-throughput screening.

  11. Targeting leukemic side population cells by isatin derivatives of nicotinic acid amide.

    PubMed

    Naglah, A M; Shinwari, Z; Bhat, M A; Al-Tahhan, M; Al-Omar, M A; Al-Dhfyan, A

    2016-01-01

    Side population (SP) cells mediate chemoresistance in leukemia. However, chemical inhibition approach to target SP cells has been poorly studied. Herein, we report the discovery of isatin derivatives of nicotinic acid amide as potent side population cell inhibitors. The selected derivatives showed superior potency over the reference drug verapamil. Furthermore, the treatment increased chemosensitivity and inhibited the cell proliferation on three different leukemic cell lines, K562, THP-1 and U937, suggesting that both SP and the bulk of leukemic cells are affected. Moreover, treatment with the most potent compound Nic9 reduced the expression of ABCG2, demonstrating that side population inhibition effect of the target derivatives is at least via ABCG2 inhibition. Importantly, the target derivatives induced erythrocyte/dendritic differentiation to leukemic cells mainly through Musashi/Numb pathway modulation. PMID:27358121

  12. GC AND LC CHROMATOGRAPHIC AND EI, CE, +/- CI, AND ES MASS SPECTRAL CHARACTERISTICS OF SALTS AND AMIDES OF PERFLUOROOCTANESULFONIC ACID

    EPA Science Inventory

    In 1976, fluorine in human blood serum was thought to be present as perfluorooctanic acid; however, in the 1990s it was correctly identified by LC/MS as perfluorooctanesulfonate (PFOS). PFOS was both a commercial product and an end-stage metabolite of numerous substituted amides ...

  13. Structure-activity relationships of fatty acid amide ligands in activating and desensitizing G protein-coupled receptor 119

    PubMed Central

    Kumar, Pritesh; Kumar, Akhilesh; Song, Zhao-Hui

    2016-01-01

    The purpose of the current study was to apply a high throughput assay to investigate the structure-activity relationships of fatty acid amides for activating and desensitizing G protein-coupled receptor 119, a promising therapeutic target for both type 2 diabetes and obesity. A cell-based, homogenous time resolved fluorescence (HTRF) method for measuring G protein-coupled receptor 119-mediated increase of cyclic adenosine monophosphate (cAMP) levels was validated and applied in this study. Using novel fatty acid amides and detailed potency and efficacy analyses, we have demonstrated that degree of saturation in acyl chain and charged head groups of fatty acid amides have profound effects on the ability of these compounds to activate G protein-coupled receptor 119. In addition, we have demonstrated for the first time that pretreatments with G protein-coupled receptor 119 agonists desensitize the receptor and the degrees of desensitization caused by fatty acid amides correlate well with their structure-activity relationships in activating the receptor. PMID:24184668

  14. Lipase-catalyzed production of a bioactive fatty amide derivative of 7,10-dihydroxy-8(E)-octadecenoic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty amides are of considerable interest due to their wide ranging industrial applications in detergents, shampoo, cosmetics and surfactant formulations. They are produced commercially from fatty acids by reacting with anhydrous ammonia at approximately 200 deg C and 345-690 KPa pressure. We inve...

  15. One-Carbon Homologation of Primary Alcohols to Carboxylic Acids, Esters, and Amides via Mitsunobu Reactions with MAC Reagents.

    PubMed

    Kagawa, Natsuko; Nibbs, Antoinette E; Rawal, Viresh H

    2016-05-20

    A method is reported for the one-carbon homologation of an alcohol to the extended carboxylic acid, ester, or amide. The process involves the Mitsunobu reaction with an alkoxymalononitrile, followed by unmasking in the presence of a suitable nucleophile. The homologation and unmasking can even be performed in a one-pot process in high yield. PMID:27135854

  16. Fatty Acid Amide Hydrolase (FAAH) Inhibition Enhances Memory Acquisition through Activation of PPAR-alpha Nuclear Receptors

    ERIC Educational Resources Information Center

    Mazzola, Carmen; Medalie, Julie; Scherma, Maria; Panlilio, Leigh V.; Solinas, Marcello; Tanda, Gianluigi; Drago, Filippo; Cadet, Jean Lud; Goldberg, Steven R.; Yasar, Sevil

    2009-01-01

    Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB[subscript 1]-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain.…

  17. Rapid, Structure-Based Exploration of Pipecolic Acid Amides as Novel Selective Antagonists of the FK506-Binding Protein 51.

    PubMed

    Gaali, Steffen; Feng, Xixi; Hähle, Andreas; Sippel, Claudia; Bracher, Andreas; Hausch, Felix

    2016-03-24

    The FK506-binding protein 51 (FKBP51) is a key regulator of stress hormone receptors and an established risk factor for stress-related disorders. Drug development for FKBP51 has been impaired by the structurally similar but functionally opposing homologue FKBP52. High selectivity between FKBP51 and FKBP52 can be achieved by ligands that stabilize a recently discovered FKBP51-favoring conformation. However, drug-like parameters for these ligands remained unfavorable. In the present study, we replaced the potentially labile pipecolic ester group of previous FKBP51 ligands by various low molecular weight amides. This resulted in the first series of pipecolic acid amides, which had much lower molecular weights without affecting FKBP51 selectivity. We discovered a geminally substituted cyclopentyl amide as a preferred FKBP51-binding motif and elucidated its binding mode to provide a new lead structure for future drug optimization. PMID:26954324

  18. Genetic engineering activates biosynthesis of aromatic fumaric acid amides in the human pathogen Aspergillus fumigatus.

    PubMed

    Kalb, Daniel; Heinekamp, Thorsten; Lackner, Gerald; Scharf, Daniel H; Dahse, Hans-Martin; Brakhage, Axel A; Hoffmeister, Dirk

    2015-03-01

    The Aspergillus fumigatus nonribosomal peptide synthetase FtpA is among the few of this species whose natural product has remained unknown. Both FtpA adenylation domains were characterized in vitro. Fumaric acid was identified as preferred substrate of the first and both l-tyrosine and l-phenylalanine as preferred substrates of the second adenylation domain. Genetically engineered A. fumigatus strains expressed either ftpA or the regulator gene ftpR, encoded in the same cluster of genes, under the control of the doxycycline-inducible tetracycline-induced transcriptional activation (tet-on) cassette. These strains produced fumaryl-l-tyrosine and fumaryl-l-phenylalanine which were identified by liquid chromatography and high-resolution mass spectrometry. Modeling of the first adenylation domain in silico provided insight into the structural requirements to bind fumaric acid as peptide synthetase substrate. This work adds aromatic fumaric acid amides to the secondary metabolome of the important human pathogen A. fumigatus which was previously not known as a producer of these compounds.

  19. The Molecular Basis for Dual Fatty Acid Amide Hydrolase (FAAH)/Cyclooxygenase (COX) Inhibition

    PubMed Central

    Palermo, Giulia; Favia, Angelo D.; Convertino, Marino

    2015-01-01

    Abstract The design of multitarget‐directed ligands is a promising strategy for discovering innovative drugs. Here, we report a mechanistic study that clarifies key aspects of the dual inhibition of the fatty acid amide hydrolase (FAAH) and the cyclooxygenase (COX) enzymes by a new multitarget‐directed ligand named ARN2508 (2‐[3‐fluoro‐4‐[3‐(hexylcarbamoyloxy)phenyl]phenyl]propanoic acid). This potent dual inhibitor combines, in a single scaffold, the pharmacophoric elements often needed to block FAAH and COX, that is, a carbamate moiety and the 2‐arylpropionic acid functionality, respectively. Molecular modeling and molecular dynamics simulations suggest that ARN2508 uses a noncovalent mechanism of inhibition to block COXs, while inhibiting FAAH via the acetylation of the catalytic Ser241, in line with previous experimental evidence for covalent FAAH inhibition. This study proposes the molecular basis for the dual FAAH/COX inhibition by this novel hybrid scaffold, stimulating further experimental studies and offering new insights for the rational design of novel anti‐inflammatory agents that simultaneously act on FAAH and COX. PMID:26593700

  20. Genetic Engineering Activates Biosynthesis of Aromatic Fumaric Acid Amides in the Human Pathogen Aspergillus fumigatus

    PubMed Central

    Kalb, Daniel; Heinekamp, Thorsten; Lackner, Gerald; Scharf, Daniel H.; Dahse, Hans-Martin; Brakhage, Axel A.

    2014-01-01

    The Aspergillus fumigatus nonribosomal peptide synthetase FtpA is among the few of this species whose natural product has remained unknown. Both FtpA adenylation domains were characterized in vitro. Fumaric acid was identified as preferred substrate of the first and both l-tyrosine and l-phenylalanine as preferred substrates of the second adenylation domain. Genetically engineered A. fumigatus strains expressed either ftpA or the regulator gene ftpR, encoded in the same cluster of genes, under the control of the doxycycline-inducible tetracycline-induced transcriptional activation (tet-on) cassette. These strains produced fumaryl-l-tyrosine and fumaryl-l-phenylalanine which were identified by liquid chromatography and high-resolution mass spectrometry. Modeling of the first adenylation domain in silico provided insight into the structural requirements to bind fumaric acid as peptide synthetase substrate. This work adds aromatic fumaric acid amides to the secondary metabolome of the important human pathogen A. fumigatus which was previously not known as a producer of these compounds. PMID:25527545

  1. Acid-promoted chemoselective introduction of amide functionality onto aromatic compounds mediated by an isocyanate cation generated from carbamate.

    PubMed

    Sumita, Akinari; Kurouchi, Hiroaki; Otani, Yuko; Ohwada, Tomohiko

    2014-10-01

    Carbamates have been used as precursors of isocyanates, but heating in the presence of strong acids is required because cleavage of the C-O bond in carbamates is energy-demanding even in acid media. Direct amidation of aromatic compounds by isocyanate cations generated at room temperature from carbamoyl salicylates in trifluoromethanesulfonic acid (TfOH) was examined. Carbamates with ortho-salicylate as an ether group (carbamoyl salicylates) showed dramatically accelerated O-C bond dissociation in TfOH, which resulted in facile generation of the isocyanate cation. These chemoselective intermolecular aromatic amidation reactions proceeded even at room temperature and showed good compatibility with other electrophilic functionalities and high discrimination between N-monosubstituted carbamate and N,N-disubstituted carbamate. The reaction rates of secondary and tertiary amide formation were markedly different, and this difference was utilized to achieve successive (tandem) amidation reactions of molecules with an N-monosubstituted carbamate and an N,N-disubstituted carbamate with two kinds of aromatic compounds.

  2. Wound-Inducible Biosynthesis of Phytoalexin Hydroxycinnamic Acid Amides of Tyramine in Tryptophan and Tyrosine Decarboxylase Transgenic Tobacco Lines1

    PubMed Central

    Guillet, Gabriel; De Luca, Vincenzo

    2005-01-01

    The wound-activated biosynthesis of phytoalexin hydroxycinnamic acid amides of tyramine was compared in untransformed and transgenic tobacco (Nicotiana tabacum) lines that express tryptophan decarboxylase (TDC), tyrosine decarboxylase (TYDC), or both activities. Transgenic in vitro-grown tobacco lines expressing TDC activity accumulated high levels of tryptamine but not hydroxycinnamic amides of tryptamine. In contrast, transgenic tobacco lines expressing TYDC accumulated tyramine as well as p-coumaroyltyramine and feruloyltyramine. The MeOH-soluble and cell wall fractions showed higher concentrations of wound-inducible p-coumaroyltyramine and feruloyltyramine, especially at and around wound sites, in TYDC and TDC ×TYDC tobacco lines compared to wild-type or TDC lines. All the enzymes involved in the biosynthesis of hydroxycinnamic acid amides of tyramine were found to be similarly wound inducible in all tobacco genotypes investigated. These results provide experimental evidence that, under some circumstances, TYDC activity can exert a rate-limiting control over the carbon flux allocated to the biosynthesis of hydroxycinnamic acid amides of tyramine. PMID:15665252

  3. Complex investigation of the effects of lambertianic acid amide in female mice under conditions of social discomfort.

    PubMed

    Avgustinovich, D F; Fomina, M K; Sorokina, I V; Tolstikova, T G

    2014-09-01

    The effects of chronic administration of a new substance lambertianic acid amide and previously synthesized methyl ester of this acid were compared in female mice living under conditions of social discomfort. For modeling social discomfort, female mouse was housed for 30 days in a cage with aggressive male mouse kept behind a transparent perforated partition and observed its confrontations with another male mouse daily placed to the cage. The new agent more effectively than lambertianic acid methyl ester improved communicativeness and motor activity of animals, reduced hypertrophy of the adrenal glands, and enhanced catalase activity in the blood. These changes suggest that lambertianic acid amide produces a pronounced stress-protective effect under conditions of social discomfort.

  4. Synthesis of biaryl imino/keto carboxylic acids via aryl amide directed C-H activation reaction.

    PubMed

    Zhang, Nana; Yu, Qingzhen; Chen, Ruixue; Huang, Jianhui; Xia, Yeqing; Zhao, Kang

    2013-10-21

    A novel Pd-catalysed C-H activation reaction for the synthesis of biaryl imino/keto carboxylic acids is developed. This reaction underwent aryl amide directed C-H activation ortho-acylation followed by ring closing and ring opening processes to give a range of biaryl imino/keto carboxylic acids. Our methodology features the utilization of a cheap and green oxidant (TBHP) as well as readily available aldehydes.

  5. Cu(I)-catalyzed (11)C carboxylation of boronic acid esters: a rapid and convenient entry to (11)C-labeled carboxylic acids, esters, and amides.

    PubMed

    Riss, Patrick J; Lu, Shuiyu; Telu, Sanjay; Aigbirhio, Franklin I; Pike, Victor W

    2012-03-12

    Rapid and direct: the carboxylation of boronic acid esters with (11)CO(2) provides [(11)C]carboxylic acids as a convenient entry into [(11)C]esters and [(11)C]amides. This conversion of boronates is tolerant to diverse functional groups (e.g., halo, nitro, or carbonyl). PMID:22308017

  6. Synthesis and application of acid labile anchor groups for the synthesis of peptide amides by Fmoc-solid-phase peptide synthesis.

    PubMed

    Breipohl, G; Knolle, J; Stüber, W

    1989-10-01

    The preparation and application of a new linker for the synthesis of peptide amides using a modified Fmoc-method is described. The new anchor group was developed based on our experience with 4,4'-dimethoxybenzhydryl (Mbh)-protecting group for amides. Lability towards acid treatment was increased dramatically and results in an easy cleavage procedure for the preparation of peptide amides. The synthesis of N-9-fluorenylmethoxycarbonyl- ([5-carboxylatoethyl-2.4-dimethoxyphenyl)- 4'-methoxyphenyl]-methylamin is reported in detail. This linker was coupled to a commercially available aminomethyl polystyrene resin. Peptide synthesis proceeded smoothly using HOOBt esters of Fmoc-amino acids. Release of the peptide amide and final cleavage of the side chain protecting groups was accomplished by treatment with trifluoroacetic acid-dichloromethane mixtures in the presence of scavengers. The synthesis of peptide amides such as LHRH and C-terminal hexapeptide of secretin are given as examples.

  7. Pd-Catalyzed Coupling of γ-C(sp(3))-H Bonds of Oxalyl Amide-Protected Amino Acids with Heteroaryl and Aryl Iodides.

    PubMed

    Han, Jian; Zheng, Yongxiang; Wang, Chao; Zhu, Yan; Huang, Zhi-Bin; Shi, Da-Qing; Zeng, Runsheng; Zhao, Yingsheng

    2016-07-01

    Pd-catalyzed regioselective coupling of γ-C(sp(3))-H bonds of oxalyl amide-protected amino acids with heteroaryl and aryl iodides is reported. A wide variety of iodides are tolerated, giving the corresponding products in moderate to good yields. Various oxalyl amide-protected amino acids were compatible in this C-H transformation, thus representing a practical method for constructing non-natural amino acid derivatives. PMID:27286881

  8. Inhibitors of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase: New Targets for Future Antidepressants.

    PubMed

    Ogawa, Shintaro; Kunugi, Hiroshi

    2015-01-01

    Cannabis and analogs of Δ9-tetrahydrocannabinol have been used for therapeutic purposes, but their therapeutic use remains limited because of various adverse effects. Endogenous cannabinoids have been discovered, and dysregulation of endocannabinoid signaling is implicated in the pathophysiology of major depressive disorder (MDD). Recently, endocannabinoid hydrolytic enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have become new therapeutic targets in the treatment of MDD. Several FAAH or MAGL inhibitors are reported to have no cannabimimetic side effects and, therefore, are new potential therapeutic options for patients with MDD who are resistant to first-line antidepressants (selective serotonin and serotonin-norepinephrine reuptake inhibitors). In this review, we focus on the possible relationships between MDD and the endocannabinoid system as well as the inhibitors' therapeutic potential. MAGL inhibitors may reduce inflammatory responses through activation of cannabinoid receptor type 2. In the hypothalamic-pituitary-adrenal axis, repeated FAAH inhibitor administration may be beneficial for reducing circulating glucocorticoid levels. Both FAAH and MAGL inhibitors may contribute to dopaminergic system regulation. Recently, several new inhibitors have been developed with strong potency and selectivity. FAAH inhibitor, MAGL inhibitor, or dual blocker use would be promising new treatments for MDD. Further pre-clinical studies and clinical trials using these inhibitors are warranted. PMID:26630956

  9. Electrospray ionization and collision induced dissociation mass spectrometry of primary fatty acid amides.

    PubMed

    Divito, Erin B; Davic, Andrew P; Johnson, Mitchell E; Cascio, Michael

    2012-03-01

    Primary fatty acid amides are a group of bioactive lipids that have been linked with a variety of biological processes such as sleep regulation and modulation of monoaminergic systems. As novel forms of these molecules continue to be discovered, more emphasis will be placed on selective, trace detection. Currently, there is no published experimental determination of collision induced dissociation of PFAMs. A select group of PFAM standards, 12 to 22 length carbon chains, were directly infused into an electrospray ionization source Quadrupole Time of Flight Mass Spectrometer. All standards were monitored in positive mode using the [M + H](+) peak. Mass Hunter Qualitative Analysis software was used to calculate empirical formulas of the product ions. All PFAMs showed losses of 14 m/z indicative of an acyl chain, while the monounsaturated group displayed neutral losses corresponding to H(2)O and NH(3). The resulting spectra were used to propose fragmentation mechanisms. Isotopically labeled PFAMs were used to validate the proposed mechanisms. Patterns of saturated versus unsaturated standards were distinctive, allowing for simple differentiation. This determination will allow for fast, qualitative identification of PFAMs. Additionally, it will provide a method development tool for selection of unique product ions when analyzed in multiple reaction monitoring mode.

  10. Effect of beta-adrenoceptors on the behaviour induced by the neuropeptide glutamic acid isoleucine amide.

    PubMed

    Sánchez-Borzone, Mariela E; Attademo, Andrés; Baiardi, Gustavo; Celis, María Ester

    2007-07-30

    Excessive grooming behaviour is induced by intracerebroventricular injections of the neuropeptide glutamic acid isoleucine amide (neuropeptide-EI), via the activation of A-10 dopaminergic neurons and the noradrenergic system. Our object was to study the latter system involved in these behaviours, using male Wistar rats weighing 250-300 g with i.c.v. implants. The results show that all the adrenoceptor antagonists "per se" do not affect excessive grooming behaviour or motor activity. Intracerebroventricular administration of propranolol, a general beta-adrenoceptor antagonist, before neuropeptide-EI, inhibited the induced excessive grooming behaviour in a dose dependent manner. Metoprolol, a beta(1)-adrenoceptor antagonist, also blocked this behaviour. However, intracerebroventricular injections of phentolamine, an alpha-adrenoceptor antagonist, and ((+/-)-1-[2,3-(Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol), a beta(2)-adrenoceptor antagonist, had no effect on the behaviour induced by neuropeptide-EI induced behaviour for any of the doses tested. On the other hand, isoproterenol, a general beta-adrenoceptor agonist and dobutamine, a beta(1)-adrenoceptor agonist, both elicited similar behaviours as those induced by neuropeptide-EI. These results support the hypothesis that a relationship exists between neuropeptide-EI and beta-adrenoceptors, more specifically the beta(1)-adrenoceptor, as found with other similar endogenous peptides such as neurotensin, cholecystin, substance P and alpha-melanocyte stimulating hormone. Hence, neuropeptide-EI could probably be exerting a neuromodulating effect on the central nervous system.

  11. Inhibitors of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase: New Targets for Future Antidepressants

    PubMed Central

    Ogawa, Shintaro; Kunugi, Hiroshi

    2015-01-01

    Cannabis and analogs of Δ9-tetrahydrocannabinol have been used for therapeutic purposes, but their therapeutic use remains limited because of various adverse effects. Endogenous cannabinoids have been discovered, and dysregulation of endocannabinoid signaling is implicated in the pathophysiology of major depressive disorder (MDD). Recently, endocannabinoid hydrolytic enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have become new therapeutic targets in the treatment of MDD. Several FAAH or MAGL inhibitors are reported to have no cannabimimetic side effects and, therefore, are new potential therapeutic options for patients with MDD who are resistant to first-line antidepressants (selective serotonin and serotonin-norepinephrine reuptake inhibitors). In this review, we focus on the possible relationships between MDD and the endocannabinoid system as well as the inhibitors’ therapeutic potential. MAGL inhibitors may reduce inflammatory responses through activation of cannabinoid receptor type 2. In the hypothalamic–pituitary–adrenal axis, repeated FAAH inhibitor administration may be beneficial for reducing circulating glucocorticoid levels. Both FAAH and MAGL inhibitors may contribute to dopaminergic system regulation. Recently, several new inhibitors have been developed with strong potency and selectivity. FAAH inhibitor, MAGL inhibitor, or dual blocker use would be promising new treatments for MDD. Further pre-clinical studies and clinical trials using these inhibitors are warranted. PMID:26630956

  12. Amide-conjugated indole-3-acetic acid and adventitious root formation in mung bean cuttings

    SciTech Connect

    Norcini, J.G.

    1986-01-01

    The purpose of this research was to investigate further the relationship between amide-conjugated auxin and adventitious root formation. Indoleacetylaspartic acid (IAA-aspartate) was positively identified as the predominant conjugate isolated from mung bean cuttings after the cuttings has been treated with 10/sup -3/ M IAA. In cuttings treated with (1-/sup 14/C)IAA immediately after excision (0 hr), the percent of extractable /sup 14/C in IAA-aspartate in the hypocotyl sharply increased until 36 hr, then steadily declined. (/sup 14/C)IAA was completely metabolized between 12 and 24 hr. The rooting activities of IAA-L-aspartate, IAA-L-alanine, and IAA-glycine were determined at various stages of root formation; some cuttings were pretreated with 10/sup -3/ M IAA at 0 hr. Pretreated cuttings that were treated with IAA-glycine at 12, 24, 36 hr exhibited the greatest consistency between replications, the greatest number of long roots, and the longest roots. The conjugates did not stimulate rooting as effectively as IAA, yet like IAA, generally enhanced rooting the greatest when applied before the first cell division (24 hr).

  13. Fatty-acid amide hydrolase polymorphisms and post-traumatic stress disorder after penetrating brain injury.

    PubMed

    Pardini, M; Krueger, F; Koenigs, M; Raymont, V; Hodgkinson, C; Zoubak, S; Goldman, D; Grafman, J

    2012-01-01

    The past few years have seen an increase in the clinical awareness of post-traumatic stress disorder (PTSD), one of the most disabling and least understood behavioral disorders. Although the biological bases of PTSD are poorly understood, fatty-acid amide hydrolase (FAAH) activity has been linked with arousability and aversive-memories extinction, that is, two key features of PTSD. In this study, we investigated the association between the FAAH genetic polymorphisms and PTSD development and maintenance. We assessed PTSD frequency in a group of male Vietnam war veterans who suffered combat-related penetrating traumatic brain injury, that is, a relatively homogeneous population regarding the nature of the events that led to PTSD. We showed that rs2295633, a single-nucleotide polymorphism of FAAH, was significantly associated with PTSD diagnosis in subjects without lesions in the ventromedial prefrontal cortex. Moreover, the presence of the C allele was associated with more severe re-experiencing of trauma and more negative reported childhood experiences. In conclusion, our data suggest that FAAH has an important role in PTSD through modulation of aversive memories and point to both a novel therapeutic target and a possible risk marker for this condition. PMID:22832737

  14. Yakushinamides, Polyoxygenated Fatty Acid Amides That Inhibit HDACs and SIRTs, from the Marine Sponge Theonella swinhoei.

    PubMed

    Takada, Kentaro; Imae, Yasufumi; Ise, Yuji; Ohtsuka, Susumu; Ito, Akihiro; Okada, Shigeru; Yoshida, Minoru; Matsunaga, Shigeki

    2016-09-23

    Yakushinamides A (1) and B (2), prolyl amides of polyoxygenated fatty acids, have been isolated from the marine sponge Theonella swinhoei as inhibitors of HDACs and SIRTs. Their planar structures were determined by interpretation of the NMR data of the intact molecules and tandem FABMS data of the methanolysis products. For the assignment of the relative configurations of the three contiguous oxymethine carbons in 1 and 2, Kishi's universal NMR database was applied to the methanolysis products. During the assignments of relative configurations of the isolated 1-hydroxy-3-methyl moiety in 1 and the isolated 1-hydroxy-2-methyl moiety in 2, we found diagnostic NMR features to distinguish each pair of diastereomers. The absolute configurations of 1 and 2 were determined by a combination of the modified Mosher's method and Marfey's method. Although the modified Mosher's method was successfully applied to the methanolysis product of 1, this method gave an ambiguous result at C-20 when applied to the methanolysis product of 2, even after oxidative cleavage of the C-14 and C-15 bond. PMID:27548648

  15. Inhibition of fatty acid amide hydrolase and cyclooxygenase by the N-(3-methylpyridin-2-yl)amide derivatives of flurbiprofen and naproxen.

    PubMed

    Cipriano, Mariateresa; Björklund, Emmelie; Wilson, Alan A; Congiu, Cenzo; Onnis, Valentina; Fowler, Christopher J

    2013-11-15

    Inhibitors of the metabolism of the endogenous cannabinoid ligand anandamide by fatty acid amide hydrolase (FAAH) reduce the gastric damage produced by non-steroidal anti-inflammatory agents and synergise with them in experimental pain models. This motivates the design of compounds with joint FAAH/cyclooxygenase (COX) inhibitory activity. Here we present data on the N-(3-methylpyridin-2-yl)amide derivatives of flurbiprofen and naproxen (Flu-AM1 and Nap-AM1, respectively) with respect to their properties towards these two enzymes. Flu-AM1 and Nap-AM1 inhibited FAAH-catalysed hydrolysis of [(3)H]anandamide by rat brain homogenates with IC50 values of 0.44 and 0.74 µM. The corresponding values for flurbiprofen and naproxen were 29 and >100 µM, respectively. The inhibition by Flu-AM1 was reversible, mixed-type, with K(i)slope and K(i)intercept values of 0.21 and 1.4 µM, respectively. Flurbiprofen and Flu-AM1 both inhibited COX in the same manner with the order of potencies COX-2 vs. 2-arachidonoylglycerol>COX-1 vs. arachidonic acid>COX-2 vs. arachidonic acid with flurbiprofen being approximately 2-3 fold more potent than Flu-AM1 in the assays. Nap-AM1 was a less potent inhibitor of COX. Flu-AM1 at low micromolar concentrations inhibited the FAAH-driven uptake of [(3)H]anandamide into RBL2H3 basophilic leukaemia cells in vitro, but did not penetrate the brain in vivo sufficiently to block the binding of [(18)F]DOPP to brain FAAH. It is concluded that Flu-AM1 is a dual-action inhibitor of FAAH and COX that may be useful in exploring the optimal balance of effects on these two enzyme systems in producing peripheral alleviation of pain and inflammation in experimental models.

  16. Changes in Pool Sizes of Free Amino Acids and Amides in Leaves and Plastids of Zea mays during Leaf Development.

    PubMed

    Chapman, D J; Leech, R M

    1979-03-01

    The concentrations of free amino acids and amides within isolated maize (Zea mays L.) plastids were determined and compared with concentrations in the leaf tissue. The concentrations were different for each individual amino acid and varied between 1 and 10 millimolar. At five different developmental stages concentrations in the plastids were greater than those in the intact leaf tissue. During development, from the proplastid stage to the mature chloroplast, the amount of each amino acid per plastid remained relatively constant, but there were decreases in concentrations of plastid amino acids resulting from the developmental increase in plastid volume. In proplastids, the free amino acids were present in greater concentrations than those previously found to inhibit partially amino acid-synthesizing enzymes located in chloroplasts. In the chloroplasts, the molarities of the free amino acids were within the range known to inhibit amino acid-synthesizing enzymes.

  17. Identification in pituitary tissue of a peptide alpha-amidation activity that acts on glycine-extended peptides and requires molecular oxygen, copper, and ascorbic acid.

    PubMed

    Eipper, B A; Mains, R E; Glembotski, C C

    1983-08-01

    An enzymatic activity capable of producing an alpha-amidated peptide product from its glycine-extended precursor has been identified in secretory granules of rat anterior, intermediate, and neural pituitary and bovine intermediate pituitary. High levels of endogenous inhibitors of this alpha-amidation activity have also been found in tissue homogenates. The alpha-amidation activity is totally inhibited by addition of divalent metal ion chelators such as diethyldithiocarbamate, o-phenanthroline, and EDTA; alpha-amidation activity is restored to above control levels upon addition of copper. The alpha-amidation reaction requires the presence of molecular oxygen. Of the various cofactors tested, ascorbic acid was the most potent stimulator of alpha-amidation. The alpha-amidation activity has a neutral pH optimum and is primarily soluble following several cycles of freezing and thawing. Kinetic studies with the bovine intermediate pituitary granule-associated activity demonstrated a linear Lineweaver-Burk plot when D-Tyr-Val-Gly was the varied substrate; the apparent Km and Vmax varied with the concentration of ascorbic acid. The substrate specificity of the alpha-amidation activity appears to be quite broad; the conversion of D-Tyr-Val-Gly into D-Tyr-Val-NH2 is inhibited by the addition of a variety of glycine-extended peptides.

  18. Analysis of lysergic acid amide in human serum and urine after ingestion of Argyreia nervosa seeds.

    PubMed

    Paulke, Alexander; Kremer, Christian; Wunder, Cora; Toennes, Stefan W

    2012-08-01

    The ergot alkaloid lysergic acid amide (LSA) is a secondary plant constituent in a number of plants, but it is mainly present in considerable amounts in Convolvulaceae, like Argyreia nervosa. Due to its close structural similarity to lysergic acid diethylamide, LSA is considered as psychedelic and therefore promoted as so-called "legal high" in various internet forums. During a human behavioral study with orally administered seeds of A. nervosa, blood and urine samples were obtained. The present study describes the validation of a sensitive and robust high performance liquid chromatography method with fluorescence detection, which was applied to the study samples. The limit of detection (LOD) and lower limit of quantification in human serum were 0.05 and 0.17 ng/mL, respectively, and in urine, the LOD was 0.15 ng/mL. Intra- and interday precision and accuracy were below 15 % relative standard deviation with a bias better than ±15 %. No conversion of LSA to its epimer iso-LSA was noted during analyses. The LSA concentrations in the authentic human serum samples were in the range of 0.66 to 3.15 ng/mL approximately 2 h after ingestion. In urine, LSA could be found 1-24 h after ingestion; after 48 h, no LSA could be detected. The LSA epimer iso-LSA was also detected in serum and urine in varying ratios. In conclusion, LSA serum levels in the low nanogram per milliliter range correlated with severe vegetative adverse effects (nausea, weakness, fatigue, tremor, blood pressure elevation) and a psychosis-like state, which led to study termination.

  19. Analgesic effects of fatty acid amide hydrolase inhibition in a rat model of neuropathic pain.

    PubMed

    Jhaveri, Maulik D; Richardson, Denise; Kendall, David A; Barrett, David A; Chapman, Victoria

    2006-12-20

    Cannabinoid-based medicines have therapeutic potential for the treatment of pain. Augmentation of levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is analgesic in models of acute and inflammatory pain states. The aim of this study was to determine whether local inhibition of FAAH alters nociceptive responses of spinal neurons in the spinal nerve ligation model of neuropathic pain. Electrophysiological studies were performed 14-18 d after spinal nerve ligation or sham surgery, and the effects of the FAAH inhibitor cyclohexylcarbamic acid 3-carbamoyl biphenyl-3-yl ester (URB597) on mechanically evoked responses of spinal neurons and levels of endocannabinoids were determined. Intraplantar URB597 (25 microg in 50 microl) significantly (p < 0.01) attenuated mechanically evoked responses of spinal neurons in sham-operated rats. Effects of URB597 were blocked by the cannabinoid 1 receptor (CB1) antagonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide] (30 microg in 50 microl) and the opioid receptor antagonist naloxone. URB597 treatment increased levels of anandamide, 2-arachidonyl glycerol, and oleoyl ethanolamide in the ipsilateral hindpaw of sham-operated rats. Intraplantar URB597 (25 microg in 50 microl) did not, however, alter mechanically evoked responses of spinal neurons in spinal nerve ligated (SNL) rats or hindpaw levels of endocannabinoids. Intraplantar injection of a higher dose of URB597 (100 microg in 50 microl) significantly (p < 0.05) attenuated evoked responses of spinal neurons in SNL rats but did not alter hindpaw levels of endocannabinoids. Spinal administration of URB597 attenuated evoked responses of spinal neurons and elevated levels of endocannabinoids in sham-operated and SNL rats. These data suggest that peripheral FAAH activity may be altered or that alternative pathways of metabolism have greater importance in SNL rats.

  20. Poly(carbonate–amide)s Derived from Bio-Based Resources: Poly(ferulic acid-co-tyrosine)

    PubMed Central

    2015-01-01

    Ferulic acid (FA), a bio-based resource found in fruits and vegetables, was coupled with a hydroxyl-amino acid to generate a new class of monomers to afford poly(carbonate–amide)s with potential to degrade into natural products. l-Serine was first selected as the hydroxyl-amino partner for FA, from which the activated p-nitrophenyl carbonate monomer was synthesized. Unfortunately, polymerizations were unsuccessful, and the elimination product was systematically obtained. To avoid elimination, we revised our strategy and used l-tyrosine ethyl ester, which lacks an acidic proton on the α position of the ethyl ester. Four new monomers were synthesized and converted into the corresponding poly(carbonate–amide)s with specific regioselectivities. The polymers were fully characterized through thermal and spectroscopic analyses. Preliminary fluorescent studies revealed interesting photophysical properties for the monomers and their corresponding poly(carbonate–amide)s, beyond the fluorescence characteristics of l-tyrosine and FA, making these materials potentially viable for sensing and/or imaging applications, in addition to their attractiveness as engineering materials derived from renewable resources. PMID:24839309

  1. N-Methyltaurine N-acyl amidated bile acids and deoxycholic acid in the bile of angelfish (Pomacanthidae): a novel bile acid profile in Perciform fish.

    PubMed

    Satoh Née Okihara, Rika; Saito, Tetsuya; Ogata, Hiroaki; Ohsaki, Ayumi; Iida, Takashi; Asahina, Kiyoshi; Mitamura, Kuniko; Ikegawa, Shigeo; Hofmann, Alan F; Hagey, Lee R

    2014-02-01

    Two novel N-acyl amidated bile acids, N-methyltaurine conjugated cholic acid and N-methyltaurine conjugated deoxycholic acid, were found to be major biliary bile acids in two species of angelfish the regal (Pygoplites diacanthus) and the blue-girdled (Pomacanthus navarchus) angelfish. The identification was based on their having MS and NMR spectra identical to those of synthetic standards. A survey of biliary bile acids of 10 additional species of angelfish found 7 with N-methyltaurine conjugation. In all 12 species, conjugated deoxycholic acid (known to be formed by bacterial 7-dehydroxylation of cholic acid) was a major bile acid. In all previous studies of biliary bile acids in fish, deoxycholic acid has been present in only trace proportions. In addition, bile acid conjugation with N-methyltaurine has not been detected previously in any known vertebrate. N-methyltaurine conjugated bile acids are resistant to bacterial deconjugation and dehydroxylation, and such resistance to bacterial enzymes should aid in the maintenance of high concentrations of bile acids during lipid digestion. Our findings suggest that these species of angelfish have a novel microbiome in their intestine containing anaerobic bacteria, and describe the presence of N-methyltaurine conjugated bile acids that are resistant to bacterial attack.

  2. A comparison of the effects of amide and acid groups at the C-terminus on the collision-induced dissociation of deprotonated peptides.

    PubMed

    Bokatzian-Johnson, Samantha S; Stover, Michele L; Dixon, David A; Cassady, Carolyn J

    2012-09-01

    The dissociative behavior of peptide amides and free acids was explored using low-energy collision-induced dissociation and high level computational theory. Both positive and negative ion modes were utilized, but the most profound differences were observed for the deprotonated species. Deprotonated peptide amides produce a characteristic c(m-2)(-) product ion (where m is the number of residues in the peptide) that is either absent or in low abundance in the analogous peptide acid spectrum. Peptide acids show an enhanced formation of c(m-3)(-); however, this is not generally as pronounced as c(m-2)(-) production from amides. The most notable occurrence of an amide-specific product ion is for laminin amide (YIGSR-NH(2)) and this case was investigated using several modified peptides. Mechanisms involving 6- and 9-membered ring formation were proposed, and their energetic properties were investigated using G3(MP2) molecular orbital theory calculations. For example, with C-terminal deprotonation of pentaglycine amide, formation of c(m-2)(-) and a 6-membered ring diketopiperazine neutral requires >31.6 kcal/mol, which is 26.1 kcal/mol less than the analogous process involving the peptide acid. The end group specific fragmentation of peptide amides in the negative ion mode may be useful for identifying such groups in proteomic applications.

  3. A Comparison of the Effects of Amide and Acid Groups at the C-Terminus on the Collision-Induced Dissociation of Deprotonated Peptides

    NASA Astrophysics Data System (ADS)

    Bokatzian-Johnson, Samantha S.; Stover, Michele L.; Dixon, David A.; Cassady, Carolyn J.

    2012-09-01

    The dissociative behavior of peptide amides and free acids was explored using low-energy collision-induced dissociation and high level computational theory. Both positive and negative ion modes were utilized, but the most profound differences were observed for the deprotonated species. Deprotonated peptide amides produce a characteristic cm-2 - product ion (where m is the number of residues in the peptide) that is either absent or in low abundance in the analogous peptide acid spectrum. Peptide acids show an enhanced formation of cm-3 -; however, this is not generally as pronounced as cm-2 - production from amides. The most notable occurrence of an amide-specific product ion is for laminin amide (YIGSR-NH2) and this case was investigated using several modified peptides. Mechanisms involving 6- and 9-membered ring formation were proposed, and their energetic properties were investigated using G3(MP2) molecular orbital theory calculations. For example, with C-terminal deprotonation of pentaglycine amide, formation of cm-2 - and a 6-membered ring diketopiperazine neutral requires >31.6 kcal/mol, which is 26.1 kcal/mol less than the analogous process involving the peptide acid. The end group specific fragmentation of peptide amides in the negative ion mode may be useful for identifying such groups in proteomic applications.

  4. Electrochemical reduction of nitrate in the presence of an amide

    DOEpatents

    Dziewinski, Jacek J.; Marczak, Stanislaw

    2002-01-01

    The electrochemical reduction of nitrates in aqueous solutions thereof in the presence of amides to gaseous nitrogen (N.sub.2) is described. Generally, electrochemical reduction of NO.sub.3 proceeds stepwise, from NO.sub.3 to N.sub.2, and subsequently in several consecutive steps to ammonia (NH.sub.3) as a final product. Addition of at least one amide to the solution being electrolyzed suppresses ammonia generation, since suitable amides react with NO.sub.2 to generate N.sub.2. This permits nitrate reduction to gaseous nitrogen to proceed by electrolysis. Suitable amides include urea, sulfamic acid, formamide, and acetamide.

  5. Synthesis and structural studies of amino amide salts derived from 2-(aminomethyl)benzimidazole and α-amino acids

    NASA Astrophysics Data System (ADS)

    Avila-Montiel, Concepción; Tapia-Benavides, Antonio R.; Falcón-León, Martha; Ariza-Castolo, Armando; Tlahuext, Hugo; Tlahuextl, Margarita

    2015-11-01

    2-{[(Ammoniumacetyl)amino]methyl}-1H-benzimidazol-3-ium dichloride 4, 2-{[(2-ammoniumpropanoyl)amino]methyl}-1H-benzimidazol-3-ium dichloride 5, and 2-{[(2-ammonium-3-phenylpropanoyl)amino]methyl}-1H-benzimidazol-3-ium dichloride 6 amino amides were synthesized via condensation of 2AMBZ dihydrochloride with the corresponding amino acid. Compounds 7-12 were obtained by replacing chloride ions (in salts 4-6) with nitrate or tetrachlorozincate ions. The results of X-ray diffraction crystallographic studies indicated that the geometries, charges and sizes of the anions are essential for the formation of the strong hydrogen bond interactions of compounds 4, 5, 9-12. Moreover, in most cases, the presence of water and solvent molecules stabilizes the supramolecular structures of these compounds. Nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy indicated that the presence of chloride or tetrachlorozincate anions increases the acidity of the benzimidazolic and amide groups more significantly than the presence of nitrate anions. However, Quantum Theory of Atoms in Molecules (QTAIM) computations of the crystal structures demonstrate that amino amides interact more strongly with NO3- than with Cl- and ZnCl42- anions; this difference explains the spectroscopic results.

  6. Analogs of cinnamic acid benzyl amide as nonclassical inhibitors of activated JAK2 kinase.

    PubMed

    Mielecki, Marcin; Milner-Krawczyk, Małgorzata; Grzelak, Krystyna; Mielecki, Damian; Krzysko, Krystiana A; Lesyng, Bogdan; Priebe, Waldemar

    2014-01-01

    Scaffold-based analogs of cinnamic acid benzyl amide (CABA) exhibit pleiotropic effects in cancer cells, and their exact molecular mechanism of action is under investigation. The present study is part of our systemic analysis of interactions of CABA analogs with their molecular targets. These compounds were shown to inhibit Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and JAK2/signal transducer and activator of transcription 5 (STAT5) signaling and thus are attractive scaffolds for anticancer drug design. To identify the potential mechanisms of action of this class of compounds, direct interactions of the selected CABA analogs with JAK2 kinase were examined. Inhibition of JAK2 enzymatic activity was assessed, and molecular modeling studies of selected compounds-(E)-2-cyano-N-[(S)-1-phenylethyl]-3-(pyridin-2-yl)acrylamide (WP1065), (E)-2-cyano-N-[(S)-1-phenylbutyl]- 3-(3-bromopyridin-2-yl)acrylamide (WP1130), and (E)-2-cyano-N-[(S)-1,4-diphenylbutyl]-3-(3-bromopyridin-2-yl)acrylamide (WP1702)-in the JAK2 kinase domain were used to support interpretation of the experimental data. Our results indicated that the tested CABA analogs are nonclassical inhibitors of activated (phosphorylated) JAK2, although markedly weaker than clinically tested ATP-competitive JAK2 inhibitors. Relatively small structural changes in the studied compounds affected interactions with JAK2, and their mode of action ranged from allosteric-noncompetitive to bisubstratecompetitive. These results demonstrated that direct inhibition of JAK2 enzymatic activity by the WP1065 (half-maximal inhibitory concentration [IC₅₀] = 14.8 µM), WP1130 (IC₅₀ = 3.8 µM), and WP1702 (IC₅₀ = 2.9 µM) potentially contributes, albeit minimally, to suppression of the JAK2/STAT signaling pathways in cancer cells and that additional specific structural modifications may amplify JAK2-inhibitory effects.

  7. Phenotypic assessment of THC discriminative stimulus properties in fatty acid amide hydrolase knockout and wildtype mice.

    PubMed

    Walentiny, D Matthew; Vann, Robert E; Wiley, Jenny L

    2015-06-01

    A number of studies have examined the ability of the endogenous cannabinoid anandamide to elicit Δ(9)-tetrahydrocannabinol (THC)-like subjective effects, as modeled through the THC discrimination paradigm. In the present study, we compared transgenic mice lacking fatty acid amide hydrolase (FAAH), the enzyme primarily responsible for anandamide catabolism, to wildtype counterparts in a THC discrimination procedure. THC (5.6 mg/kg) served as a discriminative stimulus in both genotypes, with similar THC dose-response curves between groups. Anandamide fully substituted for THC in FAAH knockout, but not wildtype, mice. Conversely, the metabolically stable anandamide analog O-1812 fully substituted in both groups, but was more potent in knockouts. The CB1 receptor antagonist rimonabant dose-dependently attenuated THC generalization in both groups and anandamide substitution in FAAH knockouts. Pharmacological inhibition of monoacylglycerol lipase (MAGL), the primary catabolic enzyme for the endocannabinoid 2-arachidonoylglycerol (2-AG), with JZL184 resulted in full substitution for THC in FAAH knockout mice and nearly full substitution in wildtypes. Quantification of brain endocannabinoid levels revealed expected elevations in anandamide in FAAH knockout mice compared to wildtypes and equipotent dose-dependent elevations in 2-AG following JZL184 administration. Dual inhibition of FAAH and MAGL with JZL195 resulted in roughly equipotent increases in THC-appropriate responding in both groups. While the notable similarity in THC's discriminative stimulus effects across genotype suggests that the increased baseline brain anandamide levels (as seen in FAAH knockout mice) do not alter THC's subjective effects, FAAH knockout mice are more sensitive to the THC-like effects of pharmacologically induced increases in anandamide and MAGL inhibition (e.g., JZL184).

  8. Fatty acid amide hydrolase inhibitors confer anti-invasive and antimetastatic effects on lung cancer cells

    PubMed Central

    Winkler, Katrin; Ramer, Robert; Dithmer, Sophie; Ivanov, Igor; Merkord, Jutta; Hinz, Burkhard

    2016-01-01

    Inhibition of endocannabinoid degradation has been suggested as tool for activation of endogenous tumor defense. One of these strategies lies in blockade of fatty acid amide hydrolase (FAAH) which catalyzes the degradation of endocannabinoids (anandamide [AEA], 2-arachidonoylglycerol [2-AG]) and endocannabinoid-like substances (N-oleoylethanolamine [OEA], N-palmitoylethanolamine [PEA]). This study addressed the impact of two FAAH inhibitors (arachidonoyl serotonin [AA-5HT], URB597) on A549 lung cancer cell metastasis and invasion. LC-MS analyses revealed increased levels of FAAH substrates (AEA, 2-AG, OEA, PEA) in cells incubated with either FAAH inhibitor. In athymic nude mice FAAH inhibitors were shown to elicit a dose-dependent antimetastatic action yielding a 67% and 62% inhibition of metastatic lung nodules following repeated administration of 15 mg/kg AA-5HT and 5 mg/kg URB597, respectively. In vitro, a concentration-dependent anti-invasive action of either FAAH inhibitor was demonstrated, accompanied with upregulation of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Using siRNA approaches, a causal link between the TIMP-1-upregulating and anti-invasive action of FAAH inhibitors was confirmed. Moreover, knockdown of FAAH by siRNA was shown to confer decreased cancer cell invasiveness and increased TIMP-1 expression. Inhibitor experiments point toward a role of CB2 and transient receptor potential vanilloid 1 in conferring anti-invasive effects of FAAH inhibitors and FAAH siRNA. Finally, antimetastatic and anti-invasive effects were confirmed for all FAAH substrates with AEA and OEA causing a TIMP-1-dependent anti-invasive action. Collectively, the present study provides first-time proof for an antimetastatic action of FAAH inhibitors. As mechanism of its anti-invasive properties an upregulation of TIMP-1 was identified. PMID:26930716

  9. Synergistic effects in solvent-extraction systems based on alkylsalicylic acids. I. Extraction of trivalent rare-earth metals in the presence of aliphatic amides

    SciTech Connect

    Preston, J.S.; Preez, A.C. du

    1995-07-01

    Aliphatic carboxylic acid amides were found to cause synergistic shifts in the pH{sub 50} values for the extraction of the trivalent rare-earth metals from chloride media by solutions of alkylsalicylic acids in xylene. For the different types of amide examined, the synergistic shifts for the extraction of neodymium by 3,5-diisopropylsalicylic acid (DIPSA) generally decrease in the order: R.CO.NR{sub 2}` > R.CO.NHR` > R.CO.NH{sub 2}, where R and R` are alkyl groups. With the N,N-dialkyl amides (R.CO.NR{sub 2}`) and the N-alkyl amides (R.CO.NHR`), the extent of the synergistic effect decreases with increasing chain-branching in either of the alkyl groups R and R`. For additions to 0.25 M alkylsalicylic acid, the synergistic effect increases with concentrations of up to 0.1 M amide, and decreases with higher concentrations. The extent of the synergistic shift produced by a given amide, as well as the separation in pH{sub 50} values from lanthanum to lutetium, increases with increasing steric bulk of the alkylsalicylic acid used. The separations between adjacent lanthanides are too small to be of any practical interest, however. Measurement of the solubility of salicylic acids (HA) in xylene containing various amounts of N,N-dialkyl amide (L) indicate that essentially complete formation of the HA.L adduct takes place. Treatment of metal-distribution data by slope analysis, and measurement of the solubility of the neodymium-DIPSA complex in xylene in the presence of amide suggest that the mixed-ligand complex has the stoichiometry NdA{sub 3}L{sub 2}. 18 refs., 6 figs., 3 refs.

  10. Keys to Lipid Selection in Fatty Acid Amide Hydrolase Catalysis: Structural Flexibility, Gating Residues and Multiple Binding Pockets

    PubMed Central

    Palermo, Giulia; Bauer, Inga; Campomanes, Pablo; Cavalli, Andrea; Armirotti, Andrea; Girotto, Stefania; Rothlisberger, Ursula; De Vivo, Marco

    2015-01-01

    The fatty acid amide hydrolase (FAAH) regulates the endocannabinoid system cleaving primarily the lipid messenger anandamide. FAAH has been well characterized over the years and, importantly, it represents a promising drug target to treat several diseases, including inflammatory-related diseases and cancer. But its enzymatic mechanism for lipid selection to specifically hydrolyze anandamide, rather than similar bioactive lipids, remains elusive. Here, we clarify this mechanism in FAAH, examining the role of the dynamic paddle, which is formed by the gating residues Phe432 and Trp531 at the boundary between two cavities that form the FAAH catalytic site (the “membrane-access” and the “acyl chain-binding” pockets). We integrate microsecond-long MD simulations of wild type and double mutant model systems (Phe432Ala and Trp531Ala) of FAAH, embedded in a realistic membrane/water environment, with mutagenesis and kinetic experiments. We comparatively analyze three fatty acid substrates with different hydrolysis rates (anandamide > oleamide > palmitoylethanolamide). Our findings identify FAAH’s mechanism to selectively accommodate anandamide into a multi-pocket binding site, and to properly orient the substrate in pre-reactive conformations for efficient hydrolysis that is interceded by the dynamic paddle. Our findings therefore endorse a structural framework for a lipid selection mechanism mediated by structural flexibility and gating residues between multiple binding cavities, as found in FAAH. Based on the available structural data, this exquisite catalytic strategy for substrate specificity seems to be shared by other lipid-degrading enzymes with similar enzymatic architecture. The mechanistic insights for lipid selection might assist de-novo enzyme design or drug discovery efforts. PMID:26111155

  11. Reaction between drug substances and pharmaceutical excipients: formation of citric acid esters and amides of carvedilol in the solid state.

    PubMed

    Larsen, Jesper; Cornett, Claus; Jaroszewski, Jerzy W; Hansen, Steen H

    2009-01-15

    The reactivity of citric acid towards drug substances in the solid state was examined using the beta-blocker carvedilol as a model compound. The reaction mixtures were analysed by LC-MS, the reaction products were isolated by preparative HPLC, and the structures were elucidated by microprobe NMR spectroscopy. Heating a mixture of solid carvedilol and solid citric acid monohydrate for 96 h at 50 degrees C resulted in the formation of about 3% of a symmetrical ester as well as of a number of other reaction products in smaller amounts. Formation of the symmetrical ester was also observed at room temperature. At 70 degrees C, the amounts of three isomeric esters formed reached 6-8%. The minor reaction products were citric acid amides, O-acetylcarvedilol, and esters of itaconic acid.

  12. Quantification and enzyme targets of fatty acid amides from duckweed root exudates involved in the stimulation of denitrification.

    PubMed

    Sun, Li; Lu, Yufang; Kronzucker, Herbert J; Shi, Weiming

    2016-07-01

    Fatty acid amides from plant root exudates, such as oleamide and erucamide, have the ability to participate in strong plant-microbe interactions, stimulating nitrogen metabolism in rhizospheric bacteria. However, mechanisms of secretion of such fatty acid amides, and the nature of their stimulatory activities on microbial metabolism, have not been examined. In the present study, collection, pre-treatment, and determination methods of oleamide and erucamide in duckweed root exudates are compared. The detection limits of oleamide and erucamide by gas chromatography (GC) (10.3ngmL(-1) and 16.1ngmL(-1), respectively) are shown to be much lower than those by liquid chromatography (LC) (1.7 and 5.0μgmL(-1), respectively). Quantitative GC analysis yielded five times larger amounts of oleamide and erucamide in root exudates of Spirodela polyrrhiza when using a continuous collection method (50.20±4.32 and 76.79±13.92μgkg(-1) FW day(-1)), compared to static collection (10.88±0.66 and 15.27±0.58μgkg(-1) FW day(-1)). Furthermore, fatty acid amide secretion was significantly enhanced under elevated nitrogen conditions (>300mgL(-1)), and was negatively correlated with the relative growth rate of duckweed. Mechanistic assays were conducted to show that erucamide stimulates nitrogen removal by enhancing denitrification, targeting two key denitrifying enzymes, nitrate and nitrite reductases, in bacteria. Our findings significantly contribute to our understanding of the regulation of nitrogen dynamics by plant root exudates in natural ecosystems. PMID:27152459

  13. Quantification and enzyme targets of fatty acid amides from duckweed root exudates involved in the stimulation of denitrification.

    PubMed

    Sun, Li; Lu, Yufang; Kronzucker, Herbert J; Shi, Weiming

    2016-07-01

    Fatty acid amides from plant root exudates, such as oleamide and erucamide, have the ability to participate in strong plant-microbe interactions, stimulating nitrogen metabolism in rhizospheric bacteria. However, mechanisms of secretion of such fatty acid amides, and the nature of their stimulatory activities on microbial metabolism, have not been examined. In the present study, collection, pre-treatment, and determination methods of oleamide and erucamide in duckweed root exudates are compared. The detection limits of oleamide and erucamide by gas chromatography (GC) (10.3ngmL(-1) and 16.1ngmL(-1), respectively) are shown to be much lower than those by liquid chromatography (LC) (1.7 and 5.0μgmL(-1), respectively). Quantitative GC analysis yielded five times larger amounts of oleamide and erucamide in root exudates of Spirodela polyrrhiza when using a continuous collection method (50.20±4.32 and 76.79±13.92μgkg(-1) FW day(-1)), compared to static collection (10.88±0.66 and 15.27±0.58μgkg(-1) FW day(-1)). Furthermore, fatty acid amide secretion was significantly enhanced under elevated nitrogen conditions (>300mgL(-1)), and was negatively correlated with the relative growth rate of duckweed. Mechanistic assays were conducted to show that erucamide stimulates nitrogen removal by enhancing denitrification, targeting two key denitrifying enzymes, nitrate and nitrite reductases, in bacteria. Our findings significantly contribute to our understanding of the regulation of nitrogen dynamics by plant root exudates in natural ecosystems.

  14. Lewis Acid Catalyzed Regiospecific Cross-Dehydrative Coupling Reaction of 2-Furylcarbinols with β-Keto Amides or 4-Hydroxycoumarins: A Route to Furyl Enols.

    PubMed

    Miao, Maozhong; Luo, Yi; Li, Hongli; Xu, Xin; Chen, Zhengkai; Xu, Jianfeng; Ren, Hongjun

    2016-06-17

    Lewis acid catalyzed directly dehydrative carbon-carbon bond formation reaction of 2-furylcarbinols with β-keto amides provides a straightforward method for regioselective synthesis of (Z)-furyl enols. Moreover, this Lewis acid catalyzed cross-coupling reaction can be extended to an interesting heterocyclic version featuring a functionalized 3-furyl-4-hydroxycoumarin synthesis. PMID:27224045

  15. Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

    PubMed Central

    Surasani, Rajendra; Rao, A V Dhanunjaya; Chandrasekhar, K B

    2012-01-01

    Summary Simple and efficient procedures for palladium-catalyzed cross-coupling reactions of N-substituted 4-bromo-7-azaindole (1H-pyrrole[2,3-b]pyridine), with amides, amines, amino acid esters and phenols through C–N and C–O bond formation have been developed. The C–N cross-coupling reaction of amides, amines and amino acid esters takes place rapidly by using the combination of Xantphos, Cs2CO3, dioxane and palladium catalyst precursors Pd(OAc)2/Pd2(dba)3. The combination of Pd(OAc)2, Xantphos, K2CO3 and dioxane was found to be crucial for the C–O cross-coupling reaction. This is the first report on coupling of amides, amino acid esters and phenols with N-protected 4-bromo-7-azaindole derivatives. PMID:23209536

  16. Caffeic acid phenethyl amide ameliorates ischemia/reperfusion injury and cardiac dysfunction in streptozotocin-induced diabetic rats

    PubMed Central

    2014-01-01

    Background Caffeic acid phenethyl ester (CAPE) has been shown to protect the heart against ischemia/reperfusion (I/R) injury by various mechanisms including its antioxidant effect. In this study, we evaluated the protective effects of a CAPE analog with more structural stability in plasma, caffeic acid phenethyl amide (CAPA), on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats. Methods Type 1 diabetes mellitus was induced in Sprague–Dawley rats by a single intravenous injection of 60 mg/kg STZ. To produce the I/R injury, the left anterior descending coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. CAPA was pretreated intraperitoneally 30 minutes before reperfusion. An analog devoid of the antioxidant property of CAPA, dimethoxyl CAPA (dmCAPA), and a nitric oxide synthase (NOS) inhibitor (Nω-nitro-l-arginine methyl ester [l-NAME]) were used to evaluate the mechanism involved in the reduction of the infarct size following CAPA-treatment. Finally, the cardioprotective effect of chronic treatment of CAPA was analyzed in diabetic rats. Results Compared to the control group, CAPA administration (3 and 15 mg/kg) significantly reduced the myocardial infarct size after I/R, while dmCAPA (15 mg/kg) had no cardioprotective effect. Interestingly, pretreatment with a NOS inhibitor, (l-NAME, 3 mg/kg) eliminated the effect of CAPA on myocardial infarction. Additionally, a 4-week CAPA treatment (1 mg/kg, orally, once daily) started 4 weeks after STZ-induction could effectively decrease the infarct size and ameliorate the cardiac dysfunction by pressure-volume loop analysis in STZ-induced diabetic animals. Conclusions CAPA, which is structurally similar to CAPE, exerts cardioprotective activity in I/R injury through its antioxidant property and by preserving nitric oxide levels. On the other hand, chronic CAPA treatment could also ameliorate cardiac dysfunction in diabetic animals. PMID:24923878

  17. [Rh(III)(Cp*)]-catalyzed ortho-selective direct C(sp(2))-H bond amidation/amination of benzoic acids by N-chlorocarbamates and N-chloromorpholines. A versatile synthesis of functionalized anthranilic acids.

    PubMed

    Ng, Fo-Ning; Zhou, Zhongyuan; Yu, Wing-Yiu

    2014-04-01

    A Rh(III) -catalyzed direct ortho-CH amidation/amination of benzoic acids with N-chlorocarbamates/N-chloromorpholines was achieved, giving anthranilic acids in up to 85 % yields with excellent ortho-selectivity and functional-group tolerance. Successful benzoic acid aminations were achieved with carbamates bearing various amide groups including NHCO2 Me, NHCbz, and NHTroc (Cbz=carbobenzyloxy; Troc=trichloroethylchloroformate), as well as secondary amines, such as morpholines, piperizines, and piperidines, furnishing highly functionalized anthranilic acids. A stoichiometric reaction of a cyclometallated rhodium(III) complex of benzo[h]quinoline with a silver salt of N-chlorocarbamate afforded an amido-rhodium(III) complex, which was isolated and structurally characterized by X-ray crystallography. This finding confirmed that the CN bond formation results from the cross-coupling of N-chlorocarbamate with the aryl-rhodium(III) complex. Yet, the mechanistic details regarding the CN bond formation remain unclear; pathways involving 1,2-aryl migration and rhodium(V)- nitrene are plausible. PMID:24596116

  18. 40 CFR 721.10410 - Polyether ester acid compound with a polyamine amide (generic) (P-05-714).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... polyamine amide (generic) (P-05-714). 721.10410 Section 721.10410 Protection of Environment ENVIRONMENTAL... polyamine amide (generic) (P-05-714). (a) Chemical substance and significant new uses subject to reporting... amide (PMN P-05-714) is subject to reporting under this section for the significant new uses...

  19. 40 CFR 721.10410 - Polyether ester acid compound with a polyamine amide (generic) (P-05-714).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... polyamine amide (generic) (P-05-714). 721.10410 Section 721.10410 Protection of Environment ENVIRONMENTAL... polyamine amide (generic) (P-05-714). (a) Chemical substance and significant new uses subject to reporting... amide (PMN P-05-714) is subject to reporting under this section for the significant new uses...

  20. Intracellular Self-Assembly of Cyclic d-Luciferin Nanoparticles for Persistent Bioluminescence Imaging of Fatty Acid Amide Hydrolase.

    PubMed

    Yuan, Yue; Wang, Fuqiang; Tang, Wei; Ding, Zhanling; Wang, Lin; Liang, Lili; Zheng, Zhen; Zhang, Huafeng; Liang, Gaolin

    2016-07-26

    Fatty acid amide hydrolase (FAAH) overexpression induces several disorder symptoms in nerve systems, and therefore long-term tracing of FAAH activity in vivo is of high importance but remains challenging. Current bioluminescence (BL) methods are limited in detecting FAAH activity within 5 h. Herein, by rational design of a latent BL probe (d-Cys-Lys-CBT)2 (1), we developed a "smart" method of intracellular reduction-controlled self-assembly and FAAH-directed disassembly of its cyclic d-luciferin-based nanoparticles (i.e., 1-NPs) for persistent BL imaging of FAAH activity in vitro, in cells, and in vivo. Using aminoluciferin methyl amide (AMA), Lys-amino-d-luciferin (Lys-Luc), and amino-d-luciferin (NH2-Luc) as control BL probes, we validated that the persistent BL of 1 from luciferase-expressing cells or tumors was controlled by the activity of intracellular FAAH. With the property of long-term tracing of FAAH activity in vivo of 1, we envision that our BL precursor 1 could probably be applied for in vivo screening of FAAH inhibitors and the diagnosis of their related diseases (or disorders) in the future. PMID:27348334

  1. Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders

    PubMed Central

    Ahn, Kay; Johnson, Douglas S.; Cravatt, Benjamin F.

    2009-01-01

    Background Fatty acid amide hydrolase (FAAH) is an integral membrane enzyme that hydrolyzes the endocannabinoid anandamide and related amidated signaling lipids. Genetic or pharmacological inactivation of FAAH produces analgesic, anti-inflammatory, anxiolytic, and antidepressant phenotypes without showing the undesirable side effects of direct cannabinoid receptor agonists, indicating that FAAH may be a promising therapeutic target. Objectives This review highlights advances in the development of FAAH inhibitors of different mechanistic classes and their in vivo efficacy. Also highlighted are advances in technology for the in vitro and in vivo selectivity assessment of FAAH inhibitors employing activity-based protein profiling (ABPP) and click chemistry-ABPP, respectively. Recent reports on structure-based drug design for human FAAH generated by protein engineering using interspecies active site conversion are also discussed. Methods: The literature searches of Medline and SciFinder databases were used. Conclusions There has been tremendous progress in our understanding in FAAH and development of FAAH inhibitors with in vivo efficacy, selectivity, and drug like pharmacokinetic properties. PMID:20544003

  2. Intracellular Self-Assembly of Cyclic d-Luciferin Nanoparticles for Persistent Bioluminescence Imaging of Fatty Acid Amide Hydrolase.

    PubMed

    Yuan, Yue; Wang, Fuqiang; Tang, Wei; Ding, Zhanling; Wang, Lin; Liang, Lili; Zheng, Zhen; Zhang, Huafeng; Liang, Gaolin

    2016-07-26

    Fatty acid amide hydrolase (FAAH) overexpression induces several disorder symptoms in nerve systems, and therefore long-term tracing of FAAH activity in vivo is of high importance but remains challenging. Current bioluminescence (BL) methods are limited in detecting FAAH activity within 5 h. Herein, by rational design of a latent BL probe (d-Cys-Lys-CBT)2 (1), we developed a "smart" method of intracellular reduction-controlled self-assembly and FAAH-directed disassembly of its cyclic d-luciferin-based nanoparticles (i.e., 1-NPs) for persistent BL imaging of FAAH activity in vitro, in cells, and in vivo. Using aminoluciferin methyl amide (AMA), Lys-amino-d-luciferin (Lys-Luc), and amino-d-luciferin (NH2-Luc) as control BL probes, we validated that the persistent BL of 1 from luciferase-expressing cells or tumors was controlled by the activity of intracellular FAAH. With the property of long-term tracing of FAAH activity in vivo of 1, we envision that our BL precursor 1 could probably be applied for in vivo screening of FAAH inhibitors and the diagnosis of their related diseases (or disorders) in the future.

  3. Concerted Amidation of Activated Esters: Reaction Path and Origins of Selectivity in the Kinetic Resolution of Cyclic Amines via N-Heterocyclic Carbenes and Hydroxamic Acid Cocatalyzed Acyl Transfer

    PubMed Central

    2015-01-01

    The N-heterocyclic carbene and hydroxamic acid cocatalyzed kinetic resolution of cyclic amines generates enantioenriched amines and amides with selectivity factors up to 127. In this report, a quantum mechanical study of the reaction mechanism indicates that the selectivity-determining aminolysis step occurs via a novel concerted pathway in which the hydroxamic acid plays a key role in directing proton transfer from the incoming amine. This modality was found to be general in amide bond formation from a number of activated esters including those generated from HOBt and HOAt, reagents that are broadly used in peptide coupling. For the kinetic resolution, the proposed model accurately predicts the faster reacting enantiomer. A breakdown of the steric and electronic control elements shows that a gearing effect in the transition state is responsible for the observed selectivity. PMID:25050843

  4. Isolation and structure of the principal products of preproglucagon processing, including an amidated glucagon-like peptide.

    PubMed

    Andrews, P C; Hawke, D H; Lee, T D; Legesse, K; Noe, B D; Shively, J E

    1986-06-25

    The principal products derived from in vivo processing of anglerfish preproglucagon II were isolated and their structures determined. The structures were confirmed by a combination of automated Edman degradation, amino acid analysis, and fast atom bombardment mass spectrometry. The peptide corresponding to anglerfish preproglucagon II-(22-49) (numbering from the amino terminus of preproglucagon) was isolated intact and defines the site of signal cleavage to be between Gln-21 and Met-22. Glucagon from the anglerfish preproglucagon gene II was found to correspond to preproglucagon II-(52-80) (numbering from the amino terminus). Three forms of a glucagon-like peptide derived from preproglucagon II were also isolated. The structure of the longest form was consistent with the sequence of preproglucagon II-(89-122) deduced from the cDNA, His-Ala-Asp-Gly-Thr-Tyr-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Gln-Asp-Gln-Ala- Ala-Lys-Asp-Phe-Val-Ser-Trp-Leu-Lys-Ala-Gly-Arg-Gly-Arg-Arg-Glu. The carboxyl-terminal portion deduced from the cDNA remains intact in this form. A second form, preproglucagon II-(89-119) appears to result from proteolytic processing of the major form at the two adjacent arginine residues occurring at the carboxyl terminus. This second form has a glycine residue at its carboxyl terminus and is processed to the third form (preproglucagon II-(89-118)) which contains a carboxyl-terminal arginineamide. Radiolabeling studies in primary tissue culture support the observation that glucagon (preproglucagon II-(52-80], preproglucagon II-(89-122), and preproglucagon II-(89-119) are products of proglucagon processing in vivo. PMID:3755132

  5. Quantum mechanics/molecular mechanics modeling of fatty acid amide hydrolase reactivation distinguishes substrate from irreversible covalent inhibitors.

    PubMed

    Lodola, Alessio; Capoferri, Luigi; Rivara, Silvia; Tarzia, Giorgio; Piomelli, Daniele; Mulholland, Adrian; Mor, Marco

    2013-03-28

    Carbamate and urea derivatives are important classes of fatty acid amide hydrolase (FAAH) inhibitors that carbamoylate the active-site nucleophile Ser241. In the present work, the reactivation mechanism of carbamoylated FAAH is investigated by means of a quantum mechanics/molecular mechanics (QM/MM) approach. The potential energy surfaces for decarbamoylation of FAAH covalent adducts, derived from the O-aryl carbamate URB597 and from the N-piperazinylurea JNJ1661610, were calculated and compared to that for deacylation of FAAH acylated by the substrate oleamide. Calculations show that a carbamic group bound to Ser241 prevents efficient stabilization of transition states of hydrolysis, leading to large increments in the activation barrier. Moreover, the energy barrier for the piperazine carboxylate was significantly lower than that for the cyclohexyl carbamate derived from URB597. This is consistent with experimental data showing slowly reversible FAAH inhibition for the N-piperazinylurea inhibitor and irreversible inhibition for URB597.

  6. Potential inhibitors of L-asparagine biosynthesis. 5. Electrophilic amide analogues of (S)-2,3-diaminopropionic acid.

    PubMed

    Mokotoff, M; Logue, L W

    1981-05-01

    Three electrophilic amide analogues of (S)-2,3-diaminopropionic acid (1, DAP) have been prepared as potential inhibitors of L-asparagine synthetase (ASase, from Novikoff hepatoma, EC 6.3.5.4). DAP was selectively blocked by the carbobenzoxy (Cbz) group to give 3-N-Cbz-DAP (2a). Esterification of 2a with isobutylene afforded tert-butyl 3-N-carbobenzoxy-(S)-2,3-diaminopropionate (3a), which was then blocked at the 2 position with the tert-butoxycarbonyl (Boc) group to give tert-butyl 2-[(S)-(tert-butoxycarbonyl)amino]-3-[(carbobenzoxy)amino]propionate (4). Selective cleavage of the Cbz group by H2/Pd gave the key intermediate tert-butyl 2-N-(tert-butoxycarbonyl)-(S)-2,3-diaminopropionate (5), which was acylated, via the N-hydroxysuccinimide esters, with bromoacetic acid, dichloroacetic acid, and fumaric acid monoethyl ester to give tert-butyl 2-[(S)-(tert-butoxycarbonyl)-amino]-3-(2-bromoacetamido)propionate (6a), tert-butyl 2-[(S)-(tert-butoxycarbonyl)amino]-3-(2,2-dichloroacetamido)propionate (6b), and tert-butyl 2-[(S)-(tert-butoxycarbonyl)amino]-3-(ethoxycarbonyl)acrylamido]-propionate (6c), respectively. Deblocking of 6a-c gave the corresponding amino acids (S)-2-amino-3-(2-bromoacetamido)propionic acid hydrobromide (7a), (S)-2-amino-3-(2,2-dichloroacetamido)propionic acid (7b), and ethyl N-[(S)-2-amino-2-carboxyethyl]fumarate (7c). By a slightly different procedure, 5 was converted in two steps to (S)-2-amino-3-acetamidopropionic acid hydrobromide (7d). The inhibition of ASase by 7a-c at 1 mM was 93, 19, and 37%, respectively, while 7d was without inhibition at 2 mM. Compounds 7a-c failed to increase the life span of mice infected with B16 melanoma.

  7. Synthesis and QSAR of Fatty Acid Amide Hydrolase Inhibitors: Modulation at the N-Portion of Biphenyl-3-yl Alkylcarbamates

    PubMed Central

    Mor, Marco; Lodola, Alessio; Rivara, Silvia; Vacondio, Federica; Duranti, Andrea; Tontini, Andrea; Sanchini, Silvano; Piersanti, Giovanni; Clapper, Jason R.; King, Alvin R.; Tarzia, Giorgio; Piomelli, Daniele

    2013-01-01

    Alkylcarbamic acid biphenyl-3-yl esters are a class of fatty acid amide hydrolase (FAAH) inhibitors that comprises cyclohexylcarbamic acid 3′-carbamoylbiphenyl-3-yl ester (URB597), a compound with analgesic, anxiolytic-like and antidepressant-like properties in rat and mouse models. Here, we extended the structure-activity relationships (SARs) for this class of compounds by replacing the cyclohexyl ring of the parent compound cyclohexylcarbamic acid biphenyl-3-yl ester (URB524) (IC50, for FAAH = 63 nM) with a selected set of substituents of different size, shape, flexibility and lipophilicity. Docking experiments and Linear Interaction Energy (LIE) calculations indicated that the N-terminal group of O-arylcarbamates fits within the lipophilic region of the substrate-binding site, mimicking the arachidonoyl chain of anandamide. Significant potency improvements were observed for the β-naphthylmethyl derivative 4q (IC50 = 5.3 nM) and its 3′-carbamoylbiphenyl-3-yl ester 4z (URB880, IC50 = 0.63 nM), indicating that shape complementarity and hydrogen bonds are crucial to obtain highly potent inhibitors. PMID:18507372

  8. 1-Aryl-2-((6-aryl)pyrimidin-4-yl)amino)ethanols as competitive inhibitors of fatty acid amide hydrolase.

    PubMed

    Keith, John M; Hawryluk, Natalie; Apodaca, Richard L; Chambers, Allison; Pierce, Joan M; Seierstad, Mark; Palmer, James A; Webb, Michael; Karbarz, Mark J; Scott, Brian P; Wilson, Sandy J; Luo, Lin; Wennerholm, Michelle L; Chang, Leon; Rizzolio, Michele; Chaplan, Sandra R; Breitenbucher, J Guy

    2014-03-01

    A series of 1-aryl-2-(((6-aryl)pyrimidin-4-yl)amino)ethanols have been found to be competitive inhibitors of fatty acid amide hydrolase (FAAH). One member of this class, JNJ-40413269, was found to have excellent pharmacokinetic properties, demonstrated robust central target engagement, and was efficacious in a rat model of neuropathic pain.

  9. Catalyst-Free Three-Component Tandem CDC Cyclization: Convenient Access to Isoindolinones from Aromatic Acid, Amides, and DMSO by a Pummerer-Type Rearrangement.

    PubMed

    Wang, Peng-Min; Pu, Fan; Liu, Ke-Yan; Li, Chao-Jun; Liu, Zhong-Wen; Shi, Xian-Ying; Fan, Juan; Yang, Ming-Yu; Wei, Jun-Fa

    2016-04-25

    A catalyst-free multicomponent CDC reaction is rarely reported, especially for the intermolecular tandem CDC cyclization, which represents an important strategy for constructing cyclic compounds. Herein, a three-component tandem CDC cyclization by a Pummerer-type rearrangement to afford biologically relevant isoindolinones from aromatic acids, amides, and DMSO, is described. This intermolecular tandem reaction undergoes a C(sp(2) )-H/C(sp(3) )-H cross-dehydrogenative coupling, C-N bond formation, and intramolecular amidation. A notable feature of this novel protocol is avoiding a catalyst and additive (apart from oxidant).

  10. Catalyst-Free Three-Component Tandem CDC Cyclization: Convenient Access to Isoindolinones from Aromatic Acid, Amides, and DMSO by a Pummerer-Type Rearrangement.

    PubMed

    Wang, Peng-Min; Pu, Fan; Liu, Ke-Yan; Li, Chao-Jun; Liu, Zhong-Wen; Shi, Xian-Ying; Fan, Juan; Yang, Ming-Yu; Wei, Jun-Fa

    2016-04-25

    A catalyst-free multicomponent CDC reaction is rarely reported, especially for the intermolecular tandem CDC cyclization, which represents an important strategy for constructing cyclic compounds. Herein, a three-component tandem CDC cyclization by a Pummerer-type rearrangement to afford biologically relevant isoindolinones from aromatic acids, amides, and DMSO, is described. This intermolecular tandem reaction undergoes a C(sp(2) )-H/C(sp(3) )-H cross-dehydrogenative coupling, C-N bond formation, and intramolecular amidation. A notable feature of this novel protocol is avoiding a catalyst and additive (apart from oxidant). PMID:26998754

  11. Detection and qualitative analysis of fatty acid amides in the urine of alcoholics using HPLC-QTOF-MS.

    PubMed

    Dabur, Rajesh; Mittal, Ashwani

    2016-05-01

    Fatty acid amides (FAAs) in alcoholism lead to liver diseases. These amides have been reported in plasma and in other organs of the body, while their detection or presence in the urine is still unknown. Therefore, the focus of the current study was to detect and analyze FAAs qualitatively in urine samples of alcoholics. Furthermore, the effects of Tinospora cordifolia (hepatoprotective medicinal plant) intervention on FAA levels in moderate alcoholics were also analyzed. In the study, asymptomatic chronic alcoholics (n = 22) without chronic liver disease and nonalcoholic healthy volunteers (n = 24) with a mean age of 39 ± 2.0 years were selected. The first-pass urine and fasting blood samples were collected in the morning on day 0 and day 14 after T. cordifolia water extract (TCE) treatment and analyzed using automated biochemistry analyzer and HPLC-QTOF-MS. Results indicated the increased levels of serum triglycerides, cholesterol, and liver function enzymes in alcoholic subjects, which were significantly down-regulated by TCE intervention. Multivariate discrimination analysis of QTOF-MS data showed increased urinary levels of oleoamide (2.55-fold), palmitamide (5.6-fold), and erucamide (1.6-fold) in alcoholics as compared to control subjects. Levels of oleamide (1.8-fold), palmitamide (1.7-fold), and linoleamide (1.5-fold) were found to be increased in plasma. Treatment with TCE in alcoholics (3.0 g lyophilized water extract/day) significantly decreased the plasma and urinary levels of all FAAs except linoleamide. The HPLC-QTOF-MS approach for FAAs analysis in both urinary and plasma samples of alcoholics worked very well. Moreover, findings (i.e., increased levels of FAAs in urine and in plasma) further support other findings that these amides play a very important role in alcoholism. Further, like our previous findings, TCE proved its hepatoprotective effect against alcoholism not only by lowering the levels of these detected FAAs, but also by decreasing the

  12. HPLC/ELSD analysis of amidated bile acids: an effective and rapid way to assist continuous flow chemistry processes.

    PubMed

    Sardella, Roccaldo; Gioiello, Antimo; Ianni, Federica; Venturoni, Francesco; Natalini, Benedetto

    2012-10-15

    The employment of the flow N-acyl amidation of natural bile acids (BAs) required the in-line connection with suitable analytical tools enabling the determination of reaction yields as well as of the purity grade of the synthesized glyco- and tauro-conjugated derivatives. In this framework, a unique HPLC method was successfully established and validated for ursodeoxycholic (UDCA), chenodeoxycholic (CDCA), deoxycholic (DCA) and cholic (CA) acids, as well as the corresponding glyco- and tauro-conjugated forms. Because of the shared absence of relevant chromophoric moieties in the sample structure, an evaporative light scattering detector (ELSD) was profitably utilized for the analysis of such steroidal species. For each of the investigated compounds, all the runs were contemporarily carried out on the acidic free and the two relative conjugated variants. The different ELSD response of the free and the corresponding conjugated BAs, imposed to build-up separate calibration curves. In all the cases, very good precision (RSD% values ranging from 1.04 to 6.40% in the long-period) and accuracy (Recovery% values ranging from 96.03 to 111.14% in the long-period) values along with appreciably low LOD and LOQ values (the former being within the range 1-27 ng mL(-1) and the latter within the range 2-44 ng mL(-1)) turned out. PMID:23141350

  13. Physical Nature of Fatty Acid Amide Hydrolase Interactions with Its Inhibitors: Testing a Simple Nonempirical Scoring Model.

    PubMed

    Giedroyć-Piasecka, Wiktoria; Dyguda-Kazimierowicz, Edyta; Beker, Wiktor; Mor, Marco; Lodola, Alessio; Sokalski, W Andrzej

    2014-12-26

    Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the deactivating hydrolysis of fatty acid ethanolamide neuromodulators. FAAH inhibitors have gained considerable interest due to their possible application in the treatment of anxiety, inflammation, and pain. In the context of inhibitor design, the availability of reliable computational tools for predicting binding affinity is still a challenging task, and it is now well understood that empirical scoring functions have several limitations that in principle could be overcome by quantum mechanics. Herein, systematic ab initio analyses of FAAH interactions with a series of inhibitors belonging to the class of the N-alkylcarbamic acid aryl esters have been performed. In contrast to our earlier studies of other classes of enzyme-inhibitor complexes, reasonable correlation with experimental results required us to consider correlation effects along with electrostatic term. Therefore, the simplest comprehensive nonempirical model allowing for qualitative predictions of binding affinities for FAAH ligands consists of electrostatic multipole and second-order dispersion terms. Such a model has been validated against the relative stabilities of the benchmark S66 set of biomolecular complexes. As it does not involve parameters fitted to experimentally derived data, this model offers a unique opportunity for generally applicable inhibitor design and virtual screening. PMID:25420234

  14. Synthesis and Structure–Activity Relationships of N-(2-Oxo-3-oxetanyl)amides as N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors

    PubMed Central

    Solorzano, Carlos; Antonietti, Francesca; Duranti, Andrea; Tontini, Andrea; Rivara, Silvia; Lodola, Alessio; Vacondio, Federica; Tarzia, Giorgio; Piomelli, Daniele; Mor, Marco

    2010-01-01

    The fatty acid ethanolamides (FAEs) are a family of bioactive lipid mediators that include the endogenous agonist of peroxisome proliferator-activated receptor-α, palmitoylethanolamide (PEA). FAEs are hydrolyzed intracellularly by either fatty acid amide hydrolase or N-acylethanolamine-hydrolyzing acid amidase (NAAA). Selective inhibition of NAAA by (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide [(S)-OOPP, 7a] prevents PEA degradation in mouse leukocytes and attenuates responses to proinflammatory stimuli. Starting from the structure of 7a a series of β-lactones was prepared and tested on recombinant rat NAAA to explore structure-activity relationships (SARs) for this class of inhibitors and improve their in vitro potency. Following the hypothesis that these compounds inhibit NAAA by acylation of the catalytic cysteine, we identified several requirements for recognition at the active site and obtained new potent inhibitors. In particular, (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide (7h) was more potent than 7a at inhibiting recombinant rat NAAA activity (7a, IC50 = 420 nM; 7h, IC50 = 115 nM) in vitro and at reducing carrageenan-induced leukocyte infiltration in vivo. PMID:20604568

  15. Application of computational methods to the design of fatty acid amide hydrolase (FAAH) inhibitors based on a carbamic template structure.

    PubMed

    Lodola, Alessio; Rivara, Silvia; Mor, Marco

    2011-01-01

    Computer-aided approaches are widely used in modern medicinal chemistry to improve the efficiency of the discovery phase. Fatty acid amide hydrolase (FAAH) is a key component of the endocannabinoid system and a potential drug target for several therapeutic applications. During the past decade, different chemical classes of inhibitors, with different mechanisms of action, had been developed. Among them, alkyl carbamic acid biphenyl-3-yl esters represent a prototypical class of active site-directed inhibitors, which allowed detailed pharmacological characterization of FAAH inhibition. Both ligand- and structure-based drug design approaches have been applied to rationalize structure-activity relationships and to drive the optimization of the inhibitory potency for this class of compounds. In this chapter, we review our contribution to the discovery and optimization of therapeutically promising FAAH inhibitors, based on a carbamic template structure, which block FAAH in an irreversible manner exerting analgesic, anti-inflammatory and anxiolytic effects in animal models. The peculiar catalytic mechanism of FAAH, and the covalent interaction with carbamate-based inhibitors, prompted the application of different computer-aided tools, ranging from ligand-based approaches to docking procedures and quantum mechanics/molecular mechanics (QM/MM) hybrid techniques. Latest advancements in the field are also reported.

  16. Chiral bio-nanocomposites based on thermally stable poly(amide-imide) having phenylalanine linkages and reactive organoclay containing tyrosine amino acid.

    PubMed

    Mallakpour, Shadpour; Dinari, Mohammad

    2013-03-01

    Montmorillonite clay modified with the bio-active trifunctional L-tyrosine amino acid salt was used as a reactive organoclay (OC) for the preparation of poly(amide-imide) (PAI)/OC hybrid films. One of the functional groups of the L-tyrosine as the swelling agent formed an ionic bond with the negatively charged silicates, whereas the remaining functional groups were available for further reaction with polymer matrix. The soluble PAI with amine end groups including phenylalanine amino acid was synthesised under green condition using molten tetra-butylammonium bromide by direct polymerization reaction of chiral diacid and 2-(3,5-diaminophenyl)benzimidazole. PAI/OC bio-nanocomposites films containing different contents of OC were prepared via solution intercalation method through blending of OC with the PAI solution. X-ray diffraction and transmission electron microscopy revealed that the dispersion of silicate layers in the PAI created an exfoliated structure as a result of using the trifunctional groups of the swelling agent. The structure and thermal behavior of the synthesised materials were characterized by a range of methods, including X-ray diffraction, Fourier transform infrared spectroscopy, (1)H-NMR, electron microscopy, elemental and thermogravimetric analysis techniques. Thermogravimetric analysis results indicated that the addition of OC into the PAI matrix was increased in the thermal decomposition temperatures of the resulted bio-nanocomposites.

  17. Application of cyanuric chloride-based six new chiral derivatizing reagents having amino acids and amino acid amides as chiral auxiliaries for enantioresolution of proteinogenic amino acids by reversed-phase high-performance liquid chromatography.

    PubMed

    Bhushan, Ravi; Dixit, Shuchi

    2012-04-01

    Six dichloro-s-triazine (DCT) reagents having L-Leu, D-Phg, L-Val, L-Met, L-Ala and L-Met-NH(2) as chiral auxiliaries in cyanuric chloride were introduced for enantioseparation of 13 proteinogenic amino acids. Four other DCTs and six monochloro-s-triazine (MCT) reagents having amino acid amides as chiral auxiliaries were also synthesized. These 16 chiral derivatizing reagents (CDRs) were used for synthesis of diastereomers of all the 13 analytes using microwave irradiation, which were resolved by reversed-phase high-performance liquid chromatography (RP-HPLC) using C18 column and gradient eluting mixture of aqueous TFA and acetonitrile with UV detection at 230 nm. It required only 60-90 s for derivatization using microwave irradiation. Better resolution and lower retention times were observed for the diastereomers prepared with CDRs having amino acids as chiral auxiliaries as compared to counterparts prepared with reagents having amino acid amides as chiral auxiliaries. As the best resolution of all the 13 analytes was observed for their diastereomers prepared using the DCT reagent having L-Leu as chiral auxiliary, this CDR was further employed for derivatization of Lys, Tyr, His and Arg followed by RP-HPLC analysis of resulting diastereomers. The results are discussed in light of acid and amide groups of chiral auxiliaries constituting CDRs, electronegativities of the atoms of achiral moieties constituting CDRs and hydrophobicities of side chains of amino acids constituting CDRs and analytes.

  18. Studies on the translational and rotational motions of ionic liquids composed of N-methyl-N-propyl-pyrrolidinium (P13) cation and bis(trifluoromethanesulfonyl)amide and bis(fluorosulfonyl)amide anions and their binary systems including lithium salts

    NASA Astrophysics Data System (ADS)

    Hayamizu, Kikuko; Tsuzuki, Seiji; Seki, Shiro; Fujii, Kenta; Suenaga, Masahiko; Umebayashi, Yasuhiro

    2010-11-01

    Room-temperature ionic liquids (RTIL, IL) are stable liquids composed of anions and cations. N-methyl-N-propyl-pyrrolidinium (P13, Py13, PYR13, or mppy) is an important cation and produces stable ILs with various anions. In this study two amide-type anions, bis(trifluoromethanesulfonyl)amide [N(SO2CF3)2, TFSA, TFSI, NTf2, or Tf2N] and bis(fluorosulfonyl)amide [N(SO2F)2, FSA, or FSI], were investigated. In addition to P13-TFSA and P13-FSA, lithium salt doped samples were prepared (P13-TFSA-Li and P13-FSA-Li). The individual ion diffusion coefficients (D) and spin-lattice relaxation times (T1) were measured by H1, F19, and L7i NMR. At the same time, the ionic conductivity (σ), viscosity (η), and density (ρ) were measured over a wide temperature range. The van der Waals volumes of P13, TFSA, FSA, Li(TFSA)2, and Li(FSA)3 were estimated by molecular orbital calculations. The experimental values obtained in this study were analyzed by the classical Stokes-Einstein, Nernst-Einstein (NE), and Stokes-Einstein-Debye equations and Walden plots were also made for the neat and binary ILs to clarify physical and mobile properties of individual ions. From the temperature-dependent velocity correlation coefficients for neat P13-TFSA and P13-FSA, the NE parameter 1-ξ was evaluated. The ionicity (electrochemical molar conductivity divided by the NE conductivity from NMR) and the 1-ξ had exactly the same values. The rotational and translational motions of P13 and jump of a lithium ion are also discussed.

  19. Biphenyl-3-yl alkylcarbamates as fatty acid amide hydrolase (FAAH) inhibitors: Steric effects of N-alkyl chain on rat plasma and liver stability

    PubMed Central

    Vacondio, Federica; Silva, Claudia; Lodola, Alessio; Carmi, Caterina; Rivara, Silvia; Duranti, Andrea; Tontini, Andrea; Sanchini, Silvano; Clapper, Jason R.; Piomelli, Daniele; Tarzia, Giorgio; Mor, Marco

    2013-01-01

    Secondary alkylcarbamic acid biphenyl-3-yl esters are a class of Fatty Acid Amide Hydrolase (FAAH) inhibitors, which include the reference compounds URB597 and URB694. Given the intrinsic reactivity of the carbamate group, the in vivo potency of these molecules in rats is strongly affected by their hydrolysis in plasma or hepatic metabolism. In the present study, in vitro chemical and metabolic stability assays (rat plasma and rat liver S9 fraction) were used to investigate the structure-property relationships (SPRs) for a focused series of title compounds, where lipophilicity and steric hindrance of the carbamate N-substituent had been modulated. The resulting degradation rates indicate that a secondary or tertiary alkyl group at the carbamate nitrogen atom increases hydrolytic stability towards rat plasma esterases. The calculated solvent accessible surface area (SASA) of the carbamate fragment was employed to describe the differences observed in rate constants of hydrolysis in rat plasma (log kplasma), suggesting that stability in plasma increases if the substituent exerts a shielding effect on the carbamate carbonyl. Stability in rat liver S9 fraction is increased when a tertiary carbon is bound to the carbamate nitrogen atom, while other steric effects showed complex relationships with degradation rates. The SPRs here described may be applied at the pharmacokinetic optimization of other classes of carbamate FAAH inhibitors. PMID:21820769

  20. Cardioprotective effects of fatty acid amide hydrolase inhibitor URB694, in a rodent model of trait anxiety.

    PubMed

    Carnevali, Luca; Vacondio, Federica; Rossi, Stefano; Macchi, Emilio; Spadoni, Gilberto; Bedini, Annalida; Neumann, Inga D; Rivara, Silvia; Mor, Marco; Sgoifo, Andrea

    2015-12-14

    In humans, chronic anxiety represents an independent risk factor for cardiac arrhythmias and sudden death. Here we evaluate in male Wistar rats bred for high (HAB) and low (LAB) anxiety-related behavior, as well as non-selected (NAB) animals, the relationship between trait anxiety and cardiac electrical instability and investigate whether pharmacological augmentation of endocannabinoid anandamide-mediated signaling exerts anxiolytic-like and cardioprotective effects. HAB rats displayed (i) a higher incidence of ventricular tachyarrhythmias induced by isoproterenol, and (ii) a larger spatial dispersion of ventricular refractoriness assessed by means of an epicardial mapping protocol. In HAB rats, acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), with URB694 (0.3 mg/kg), (i) decreased anxiety-like behavior in the elevated plus maze, (ii) increased anandamide levels in the heart, (iii) reduced isoproterenol-induced occurrence of ventricular tachyarrhythmias, and (iv) corrected alterations of ventricular refractoriness. The anti-arrhythmic effect of URB694 was prevented by pharmacological blockade of the cannabinoid type 1 (CB1), but not of the CB2, receptor. These findings suggest that URB694 exerts anxiolytic-like and cardioprotective effects in HAB rats, the latter via anandamide-mediated activation of CB1 receptors. Thus, pharmacological inhibition of FAAH might be a viable pharmacological strategy for the treatment of anxiety-related cardiac dysfunction.

  1. Potent and Selective α-Ketoheterocycle-Based Inhibitors of the Anandamide and Oleamide Catabolizing Enzyme, Fatty Acid Amide Hydrolase

    PubMed Central

    Romero, F. Anthony; Du, Wu; Hwang, Inkyu; Rayl, Thomas J.; Kimball, F. Scott; Leung, Donmienne; Hoover, Heather S.; Apodaca, Richard L.; Breitenbucher, J. Guy; Cravatt, Benjamin F.; Boger, Dale L.

    2008-01-01

    A study of the structure–activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the 5-position of the oxazole. Examination of a series of substituted benzene derivatives (12–14) revealed that the optimal position for substitution was the meta-position with selected members approaching or exceeding the potency of 2f. Concurrent with these studies, the effect of substitution on the pyridine ring of 2f was also examined. A series of small, non-aromatic C5-substituents was also explored and revealed that the Ki follows a well-defined correlation with the Hammett σp constant (ρ = 3.01, R2 = 0.91) in which electron-withdrawing substituents enhance potency leading to inhibitors with Ki’s as low as 400 pM (20n). Proteomic-wide screening of the inhibitors revealed that most are exquisitely selective for FAAH over all other mammalian proteases reversing the 100-fold preference of 20a (C5 substituent = H) for the enzyme TGH. PMID:17279740

  2. Inhibition of fatty-acid amide hydrolase accelerates acquisition and extinction rates in a spatial memory task.

    PubMed

    Varvel, Stephen A; Wise, Laura E; Niyuhire, Floride; Cravatt, Benjamin F; Lichtman, Aron H

    2007-05-01

    Recent reports have demonstrated that disruption of CB(1) receptor signaling impairs extinction of learned responses in conditioned fear and Morris water maze paradigms. Here, we test the hypothesis that elevating brain levels of the endogenous cannabinoid anandamide through either genetic deletion or pharmacological inhibition of its primary catabolic enzyme fatty-acid amide hydrolase (FAAH) will potentiate extinction in a fixed platform water maze task. FAAH (-/-) mice and mice treated with the FAAH inhibitor OL-135, did not display any memory impairment or motor disruption, but did exhibit a significant increase in the rate of extinction. Unexpectedly, FAAH-compromised mice also exhibited a significant increase in acquisition rate. The CB(1) receptor antagonist SR141716 (rimonabant) when given alone had no effects on acquisition, but disrupted extinction. Additionally, SR141716 blocked the effects of OL-135 on both acquisition and extinction. Collectively, these results indicate that endogenous anandamide plays a facilitatory role in extinction through a CB(1) receptor mechanism of action. In contrast, the primary psychoactive constituent of marijuana, Delta(9)-tetrahydrocannabinol, failed to affect extinction rates, suggesting that FAAH is a more effective target than a direct acting CB(1) receptor agonist in facilitating extinction. More generally, these findings suggest that FAAH inhibition represents a promising pharmacological approach to treat psychopathologies hallmarked by an inability to extinguish maladaptive behaviors, such as post-traumatic stress syndrome and obsessive-compulsive disorder.

  3. Synthesis and antiproliferative activity of two diastereomeric lignan amides serving as dimeric caffeic acid-l-DOPA hybrids.

    PubMed

    Magoulas, George E; Rigopoulos, Andreas; Piperigkou, Zoi; Gialeli, Chrysostomi; Karamanos, Nikos K; Takis, Panteleimon G; Troganis, Anastassios N; Chrissanthopoulos, Athanassios; Maroulis, George; Papaioannou, Dionissios

    2016-06-01

    Two new diastereomeric lignan amides (4 and 5) serving as dimeric caffeic acid-l-DOPA hybrids were synthesized. The synthesis involved the FeCl3-mediated phenol oxidative coupling of methyl caffeate to afford trans-diester 1a as a mixture of enantiomers, protection of the catechol units, regioselective saponification, coupling with a suitably protected l-DOPA derivative, separation of the two diastereomers thus obtained by flash column chromatography and finally global chemoselective deprotection of the catechol units. The effect of hybrids 4 and 5 and related compounds on the proliferation of two breast cancer cell lines with different metastatic potential and estrogen receptor status (MDA-MB-231 and MCF-7) and of one epithelial lung cancer cell line, namely A-549, was evaluated for concentrations ranging from 1 to 256μM and periods of treatment of 24, 48 and 72h. Both hybrids showed interesting and almost equipotent antiproliferative activities (IC50 64-70μM) for the MDA-MB-231 cell line after 24-48h of treatment, but they were more selective and much more potent (IC50 4-16μM) for the MCF-7 cells after 48h of treatment. The highest activity for both hybrids and both breast cancer lines was observed after 72h of treatment (IC50 1-2μM), probably as the result of slow hydrolysis of their methyl ester functions. PMID:27155809

  4. The macamide N-3-methoxybenzyl-linoleamide is a time-dependent fatty acid amide hydrolase (FAAH) inhibitor.

    PubMed

    Almukadi, Haifa; Wu, Hui; Böhlke, Mark; Kelley, Charles J; Maher, Timothy J; Pino-Figueroa, Alejandro

    2013-10-01

    The Peruvian plant Lepidium meyenii (Maca) has been shown to possess neuroprotective activity both in vitro and in vivo. Previous studies have also demonstrated the activity of the pentane extract and its macamides, the most representative lipophilic constituents of Maca, in the endocannabinoid system as fatty acid amide hydrolase (FAAH) inhibitors. One of the most active macamides, N-3-methoxybenzyl-linoleamide, was studied to determine its mechanism of interaction with FAAH and whether it has inhibitory activity on mono-acyl glycerol lipase (MAGL), the second enzyme responsible for endocannabinoid degradation. Macamide concentrations from 1 to 100 μM were tested using FAAH and MAGL inhibitor assay methods and showed no effect on MAGL. Tests with other conditions were performed in order to characterize the inhibitory mechanism of FAAH inhibition. N-3-methoxybenzyl-linoleamide displayed significant time-dependent and dose-dependent FAAH inhibitory activity. The mechanism of inhibition was most likely irreversible or slowly reversible. These results suggest the potential application of macamides isolated from Maca as FAAH inhibitors, as they might act on the central nervous system to provide analgesic, anti-inflammatory, or neuroprotective effects, by modulating the release of neurotransmitters. PMID:23853040

  5. Dianthosaponins G-I, triterpene saponins, an anthranilic acid amide glucoside and a flavonoid glycoside from the aerial parts of Dianthus japonicus and their cytotoxicity.

    PubMed

    Kanehira, Yuka; Kawakami, Susumu; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki

    2016-10-01

    Extensive isolation work on the 1-BuOH-soluble fraction of a MeOH extract of the aerial parts of Dianthus japonicus afforded three further triterpene glycosyl estsers, termed dianthosaponins G-I, an anthranilic acid amide glucoside and a C-glycosyl flavonoid along with one known triterpene saponin. Their structures were elucidated from spectroscopic evidence. The cytotoxicity of the isolated compounds toward A549 cells was evaluated.

  6. Possible Evidence of Amide Bond Formation Between Sinapinic Acid and Lysine-Containing Bacterial Proteins by Matrix-Assisted Laser Desorption/Ionization (MALDI) at 355 nm

    NASA Astrophysics Data System (ADS)

    Fagerquist, Clifton K.; Sultan, Omar; Carter, Michelle Q.

    2012-12-01

    We previously reported the apparent formation of matrix adducts of 3,5-dimethoxy-4-hydroxy-cinnamic acid (sinapinic acid or SA) via covalent attachment to disulfide bond-containing proteins (HdeA, Hde, and YbgS) from bacterial cell lysates ionized by matrix-assisted laser desorption/ionization (MALDI) time-of-flight-time-of-flight tandem mass spectrometry (TOF-TOF-MS/MS) and post-source decay (PSD). We also reported the absence of adduct formation when using α-cyano-4-hydroxycinnamic acid (CHCA) matrix. Further mass spectrometric analysis of disulfide-intact and disulfide-reduced over-expressed HdeA and HdeB proteins from lysates of gene-inserted E. coli plasmids suggests covalent attachment of SA occurs not at cysteine residues but at lysine residues. In this revised hypothesis, the attachment of SA is preceded by formation of a solid phase ammonium carboxylate salt between SA and accessible lysine residues of the protein during sample preparation under acidic conditions. Laser irradiation at 355 nm of the dried sample spot results in equilibrium retrogradation followed by nucleophilic attack by the amine group of lysine at the carbonyl group of SA and subsequent amide bond formation and loss of water. The absence of CHCA adducts suggests that the electron-withdrawing effect of the α-cyano group of this matrix may inhibit salt formation and/or amide bond formation. This revised hypothesis is supported by dissociative loss of SA (-224 Da) and the amide-bound SA (-206 Da) from SA-adducted HdeA and HdeB ions by MS/MS (PSD). It is proposed that cleavage of the amide-bound SA from the lysine side-chain occurs via rearrangement involving a pentacyclic transition state followed by hydrogen abstraction/migration and loss of 3-(4-hydroxy-3,5-dimethoxyphenyl)prop-2-ynal (-206 Da).

  7. Dianthosaponins G-I, triterpene saponins, an anthranilic acid amide glucoside and a flavonoid glycoside from the aerial parts of Dianthus japonicus and their cytotoxicity.

    PubMed

    Kanehira, Yuka; Kawakami, Susumu; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki

    2016-10-01

    Extensive isolation work on the 1-BuOH-soluble fraction of a MeOH extract of the aerial parts of Dianthus japonicus afforded three further triterpene glycosyl estsers, termed dianthosaponins G-I, an anthranilic acid amide glucoside and a C-glycosyl flavonoid along with one known triterpene saponin. Their structures were elucidated from spectroscopic evidence. The cytotoxicity of the isolated compounds toward A549 cells was evaluated. PMID:27351981

  8. Impaired neurogenesis by HIV-1-Gp120 is rescued by genetic deletion of fatty acid amide hydrolase enzyme

    PubMed Central

    Avraham, H K; Jiang, S; Fu, Y; Rockenstein, E; Makriyannis, A; Wood, J; Wang, L; Masliah, E; Avraham, S

    2015-01-01

    Background and Purpose The HIV-envelope glycoprotein Gp120 is involved in neuronal injury and is associated with neuro-AIDS pathogenesis in the brain. Endocannabinoids are important lipid ligands in the CNS regulating neural functions, and their degeneration is controlled by hydrolysing enzymes such as the fatty acid amide hydrolase (FAAH). Here, we examined whether in vivo genetic deletion of Faah gene prevents HIV-1 Gp120-mediated effects on neurogenesis. Experimental Approach We generated new GFAP/Gp120 transgenic (Tg) mice that have genetic deletion of Faah gene by mating glial fribillary acidic protein (GFAP)/Gp120 Tg mice with Faah−/− mice. Neurogenesis and cell death were assessed by immunocytochemical analysis. Key Results Endocannabinoid levels in the brain of the double GFAP/Gp120//Faah−/− mice were similar to those observed in Faah−/− mice. However, unlike the impaired neurogenesis observed in GFAP/Gp120 Tg mice and Faah−/− mice, these GFAP/Gp120//Faah-/ mice showed significantly improved neurogenesis in the hippocampus, indicated by a significant increase in neuroblasts and neuronal cells, an increase in BrdU+ cells and doublecortin positive cells (DCX+), and an increase in the number of PCNA. Furthermore, a significant decrease in astrogliosis and gliogenesis was observed in GFAP/Gp120//Faah−/−mice and neurogenesis was stimulated by neural progenitor cells (NPCs) and/or the newly formed NPC niches characterized by increased COX-2 expression and elevated levels of PGE2. Conclusions and Implications In vivo genetic ablation of Faah, resulted in enhanced neurogenesis through modulation of the newly generated NPC niches in GFAP/Gp120//Faah−/− mice. This suggests a novel approach of using FAAH inhibitors to enhance neurogenesis in HIV-1 infected brain. PMID:24571443

  9. The fatty-acid amide hydrolase inhibitor URB597 does not affect triacylglycerol hydrolysis in rat tissues.

    PubMed

    Clapper, Jason R; Duranti, Andrea; Tontini, Andrea; Mor, Marco; Tarzia, Giorgio; Piomelli, Daniele

    2006-11-01

    The O-arylcarbamate URB597 (cyclohexylcarbamic acid 3'-carbamoylbiphenyl-3-yl ester; also referred to as KDS-4103) is a potent inhibitor of fatty-acid amide hydrolase (FAAH), an intracellular serine hydrolase responsible for the inactivation of the endogenous cannabinoid anandamide. URB597 demonstrates a remarkable degree of selectivity for FAAH over other serine hydrolases (e.g. cholinesterases) or other components of the endocannabinoid system (e.g. cannabinoid receptors). However, in a proteomic-based selectivity screen based on the displacement of fluorophosphonate-rhodamine (FPR) from mouse brain proteins, it was recently shown that URB597 prevents FPR binding to triacylglycerol hydrolase (TGH) with a median inhibitory concentration of 192nM. To determine whether this effect correlates with inhibition of TGH activity, we investigated the ability of URB597 to inhibit triolein hydrolysis in rat liver and heart tissues, which are rich in TGH, as well as white adipose tissue (WAT), which is rich in adipose triacylglycerol lipase (TGL) and hormone-sensitive lipase. The results show that URB597 does not affect triolein hydrolysis in any of these tissues at concentrations as high as 10microM, whereas it inhibits FAAH activity at low nanomolar concentrations. Moreover, intraperitoneal (i.p.) administration of URB597 at doses that maximally inhibit FAAH in vivo (0.3-3mgkg(-1)) exerts no effect on triolein hydrolysis and tissue triacylglycerol (TAG) levels in rat liver, heart or WAT. The results indicate that URB597, while potent at inhibiting FAAH, does not affect TGH and TGL activities in rat tissues.

  10. Effects of Fatty Acid Amide Hydrolase (FAAH) Inhibitors in Non-Human Primate Models of Nicotine Reward and Relapse

    PubMed Central

    Justinova, Zuzana; Panlilio, Leigh V; Moreno-Sanz, Guillermo; Redhi, Godfrey H; Auber, Alessia; Secci, Maria E; Mascia, Paola; Bandiera, Tiziano; Armirotti, Andrea; Bertorelli, Rosalia; Chefer, Svetlana I; Barnes, Chanel; Yasar, Sevil; Piomelli, Daniele; Goldberg, Steven R

    2015-01-01

    Inhibition of the enzyme fatty acid amide hydrolase (FAAH) counteracts reward-related effects of nicotine in rats, but it has not been tested for this purpose in non-human primates. Therefore, we studied the effects of the first- and second-generation O-arylcarbamate-based FAAH inhibitors, URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester) and URB694 (6-hydroxy-[1,1'-biphenyl]-3-yl-cyclohexylcarbamate), in squirrel monkeys. Both FAAH inhibitors: (1) blocked FAAH activity in brain and liver, increasing levels of endogenous ligands for cannabinoid and α-type peroxisome proliferator-activated (PPAR-α) receptors; (2) shifted nicotine self-administration dose–response functions in a manner consistent with reduced nicotine reward; (3) blocked reinstatement of nicotine seeking induced by reexposure to either nicotine priming or nicotine-associated cues; and (4) had no effect on cocaine or food self-administration. The effects of FAAH inhibition on nicotine self-administration and nicotine priming-induced reinstatement were reversed by the PPAR-α antagonist, MK886. Unlike URB597, which was not self-administered by monkeys in an earlier study, URB694 was self-administered at a moderate rate. URB694 self-administration was blocked by pretreatment with an antagonist for either PPAR-α (MK886) or cannabinoid CB1 receptors (rimonabant). In additional experiments in rats, URB694 was devoid of THC-like or nicotine-like interoceptive effects under drug-discrimination procedures, and neither of the FAAH inhibitors induced dopamine release in the nucleus accumbens shell—consistent with their lack of robust reinforcing effects in monkeys. Overall, both URB597 and URB694 show promise for the initialization and maintenance of smoking cessation because of their ability to block the rewarding effects of nicotine and prevent nicotine priming-induced and cue-induced reinstatement. PMID:25754762

  11. Reversible competitive α-ketoheterocycle inhibitors of fatty acid amide hydrolase containing additional conformational constraints in the acyl side chain: orally active, long-acting analgesics.

    PubMed

    Ezzili, Cyrine; Mileni, Mauro; McGlinchey, Nicholas; Long, Jonathan Z; Kinsey, Steven G; Hochstatter, Dustin G; Stevens, Raymond C; Lichtman, Aron H; Cravatt, Benjamin F; Bilsky, Edward J; Boger, Dale L

    2011-04-28

    A series of α-ketooxazoles containing conformational constraints in the C2 acyl side chain of 2 (OL-135) were examined as inhibitors of fatty acid amide hydrolase (FAAH). Only one of the two possible enantiomers displayed potent FAAH inhibition (S vs R enantiomer), and their potency is comparable or improved relative to 2, indicating that the conformational restriction in the C2 acyl side chain is achievable. A cocrystal X-ray structure of the α-ketoheterocycle 12 bound to a humanized variant of rat FAAH revealed its binding details, confirmed that the (S)-enantiomer is the bound active inhibitor, shed light on the origin of the enantiomeric selectivity, and confirmed that the catalytic Ser241 is covalently bound to the electrophilic carbonyl as a deprotonated hemiketal. Preliminary in vivo characterization of the inhibitors 12 and 14 is reported demonstrating that they raise brain anandamide levels following either intraperitoneal (ip) or oral (po) administration indicative of effective in vivo FAAH inhibition. Significantly, the oral administration of 12 caused dramatic accumulation of anandamide in the brain, with peak levels achieved between 1.5 and 3 h, and these elevations were maintained over 9 h. Additional studies of these two representative members of the series (12 and 14) in models of thermal hyperalgesia and neuropathic pain are reported, including the demonstration that 12 administered orally significantly attenuated mechanical (>6 h) and cold (>9 h) allodynia for sustained periods consistent with its long-acting effects in raising the endogenous concentration of anandamide.

  12. A novel PPARα agonist propane-2-sulfonic acid octadec-9-enyl-amide inhibits inflammation in THP-1 cells.

    PubMed

    Zhao, Yun; Yan, Lu; Luo, Xiu-Mei; Peng, Lu; Guo, Han; Jing, Zuo; Yang, Li-Chao; Hu, Rong; Wang, Xuan; Huang, Xue-Feng; Wang, Yi-Qing; Jin, Xin

    2016-10-01

    Our group synthesized propane-2-sulfonic acid octadec-9-enyl-amide (N15), a novel peroxisome proliferator activated receptor alpha (PPARα) agonist. Because PPARα activation is associated with inflammation control, we hypothesize that N15 may have anti-inflammatory effects. We investigated the effect of N15 on the regulation of inflammation in THP-1 cells stimulated with lipopolysaccharide (LPS). In particular, we assessed the production of chemokines, adhesion molecules and proinflammatory cytokines, three important types of cytokines that are released from monocytes and are involved in the development of atherosclerosis. The results showed that N15 remarkably reduced the mRNA expression of chemokines, such as monocyte chemotactic protein 1 (MCP-1 or CCL2), interleukin-8 (IL-8) and interferon-inducible protein-10 (IP-10 or CXCL10), and proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). N15 also decreased the protein expression of vascular cell adhesion molecule (VCAM) and matrix metalloproteinase (MMP) 2 and 9. The reduction in the expression of cytokine mRNAs observed following N15 treatment was abrogated in THP-1 cells treated with PPARα siRNA, indicating that the anti-inflammatory effects of N15 are dependent on PPARα activation. Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) inhibition, which are dependent on PPARα activation, were also involved in the mechanism underlying the anti-inflammatory effects of N15. In conclusion, the novel PPARα agonist, N15, exerts notable anti-inflammatory effects, which are mediated via PPARα activation and TLR4/NF-κB and STAT3 inhibition, in LPS-stimulated THP-1 cells. In our study, N15 exhibits promise for the treatment of atherosclerosis.

  13. Inhibition of fatty acid amide hydrolase activates Nrf2 signalling and induces heme oxygenase 1 transcription in breast cancer cells

    PubMed Central

    Li, H; Wood, J T; Whitten, K M; Vadivel, S K; Seng, S; Makriyannis, A; Avraham, H K

    2013-01-01

    BACKGROUND AND PURPOSE Endocannabinoids such as anandamide (AEA) are important lipid ligands regulating cell proliferation, differentiation and apoptosis. Their levels are regulated by hydrolase enzymes, the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL). Here, we investigated whether FAAH or AEA are involved in NF (erythroid-derived 2)-like 2 (Nrf2)/antioxidant responsive element (ARE) pathway. EXPERIMENTAL APPROACH The aim of this study was to analyse the effects of AEA or FAAH inhibition by the URB597 inhibitor or FAAH/siRNA on the activation of Nrf2-ARE signalling pathway and heme oxygenase-1 (HO-1) induction and transcription. KEY RESULTS Endogenous AEA was detected in the immortalized human mammary epithelial MCF-10A cells (0.034 ng per 106 cells) but not in MCF-7 or MDA-MB-231 breast cancer cells. Because breast tumour cells express FAAH abundantly, we examined the effects of FAAH on Nrf2/antioxidant pathway. We found that inhibition of FAAH by the URB597 inhibitor induced antioxidant HO-1 in breast cancer cells and MCF-10A cells. RNAi-mediated knockdown of FAAH or treatment with AEA-activated ARE-containing reporter induced HO-1 mRNA and protein expression, independent of the cannabinoid receptors, CB1, CB2 or TRPV1. Furthermore, URB597, AEA and siRNA-FAAH treatments induced the nuclear translocation of Nrf2, while siRNA-Nrf2 treatment and Keap1 expression blocked AEA, URB597 and si-FAAH from activation of ARE reporter and HO-1 induction. siRNA-HO-1 treatment decreased the viability of breast cancer cells and MCF-10A cells. CONCLUSIONS AND IMPLICATIONS These data uncovered a novel mechanism by which inhibition of FAAH or exposure to AEA induced HO-1 transcripts and implicating AEA and FAAH as direct modifiers in signalling mediated activation of Nrf2-HO-1 pathway, independent of cannabinoid receptors. PMID:23347118

  14. Disruption of fatty acid amide hydrolase activity prevents the effects of chronic stress on anxiety and amygdalar microstructure.

    PubMed

    Hill, M N; Kumar, S A; Filipski, S B; Iverson, M; Stuhr, K L; Keith, J M; Cravatt, B F; Hillard, C J; Chattarji, S; McEwen, B S

    2013-10-01

    Hyperactivation of the amygdala following chronic stress is believed to be one of the primary mechanisms underlying the increased propensity for anxiety-like behaviors and pathological states; however, the mechanisms by which chronic stress modulates amygdalar function are not well characterized. The aim of the current study was to determine the extent to which the endocannabinoid (eCB) system, which is known to regulate emotional behavior and neuroplasticity, contributes to changes in amygdalar structure and function following chronic stress. To examine the hypothesis, we have exposed C57/Bl6 mice to chronic restraint stress, which results in an increase in fatty acid amide hydrolase (FAAH) activity and a reduction in the concentration of the eCB N-arachidonylethanolamine (AEA) within the amygdala. Chronic restraint stress also increased dendritic arborization, complexity and spine density of pyramidal neurons in the basolateral nucleus of the amygdala (BLA) and increased anxiety-like behavior in wild-type mice. All of the stress-induced changes in amygdalar structure and function were absent in mice deficient in FAAH. Further, the anti-anxiety effect of FAAH deletion was recapitulated in rats treated orally with a novel pharmacological inhibitor of FAAH, JNJ5003 (50 mg per kg per day), during exposure to chronic stress. These studies suggest that FAAH is required for chronic stress to induce hyperactivity and structural remodeling of the amygdala. Collectively, these studies indicate that FAAH-mediated decreases in AEA occur following chronic stress and that this loss of AEA signaling is functionally relevant to the effects of chronic stress. These data support the hypothesis that inhibition of FAAH has therapeutic potential in the treatment of anxiety disorders, possibly by maintaining normal amygdalar function in the face of chronic stress.

  15. A novel PPARα agonist propane-2-sulfonic acid octadec-9-enyl-amide inhibits inflammation in THP-1 cells.

    PubMed

    Zhao, Yun; Yan, Lu; Luo, Xiu-Mei; Peng, Lu; Guo, Han; Jing, Zuo; Yang, Li-Chao; Hu, Rong; Wang, Xuan; Huang, Xue-Feng; Wang, Yi-Qing; Jin, Xin

    2016-10-01

    Our group synthesized propane-2-sulfonic acid octadec-9-enyl-amide (N15), a novel peroxisome proliferator activated receptor alpha (PPARα) agonist. Because PPARα activation is associated with inflammation control, we hypothesize that N15 may have anti-inflammatory effects. We investigated the effect of N15 on the regulation of inflammation in THP-1 cells stimulated with lipopolysaccharide (LPS). In particular, we assessed the production of chemokines, adhesion molecules and proinflammatory cytokines, three important types of cytokines that are released from monocytes and are involved in the development of atherosclerosis. The results showed that N15 remarkably reduced the mRNA expression of chemokines, such as monocyte chemotactic protein 1 (MCP-1 or CCL2), interleukin-8 (IL-8) and interferon-inducible protein-10 (IP-10 or CXCL10), and proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). N15 also decreased the protein expression of vascular cell adhesion molecule (VCAM) and matrix metalloproteinase (MMP) 2 and 9. The reduction in the expression of cytokine mRNAs observed following N15 treatment was abrogated in THP-1 cells treated with PPARα siRNA, indicating that the anti-inflammatory effects of N15 are dependent on PPARα activation. Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) inhibition, which are dependent on PPARα activation, were also involved in the mechanism underlying the anti-inflammatory effects of N15. In conclusion, the novel PPARα agonist, N15, exerts notable anti-inflammatory effects, which are mediated via PPARα activation and TLR4/NF-κB and STAT3 inhibition, in LPS-stimulated THP-1 cells. In our study, N15 exhibits promise for the treatment of atherosclerosis. PMID:27318324

  16. Disruption of Fatty Acid Amide Hydrolase Activity Prevents the Effects of Chronic Stress on Anxiety and Amygdalar Microstructure

    PubMed Central

    Hill, Matthew N.; Kumar, Shobha Anil; Filipski, Sarah B.; Iverson, Moriah; Stuhr, Kara L.; Keith, John M.; Cravatt, Benjamin F.; Hillard, Cecilia J.; Chattarji, Sumantra; McEwen, Bruce S.

    2014-01-01

    Hyperactivation of the amygdala following chronic stress is believed to be one of the primary mechanisms underlying the increased propensity for anxiety-like behaviors and pathological states; however, the mechanisms by which chronic stress modulates amygdalar function are not well characterized. The aim of the current study was to determine the extent to which the endocannabinoid system, which is known to regulate emotional behavior and neuroplasticity, contributes to changes in amygdalar structure and function following chronic stress. To examine the hypothesis, we have exposed C57/Bl6 mice to chronic restraint stress which results in an increase in fatty acid amide hydrolase (FAAH) activity and a reduction in the concentration of the endocannabinoid N-arachidonylethanolamine (AEA) within the amygdala. Chronic restraint stress also increased dendritic arborization, complexity and spine density of pyramidal neurons in the basolateral nucleus of the amygdala (BLA) and increased anxiety-like behavior in wild-type mice. All of the stress-induced changes in amygdalar structure and function were absent in mice deficient in FAAH. Further, the anti-anxiety effect of FAAH deletion was recapitulated in rats treated orally with a novel pharmacological inhibitor of FAAH, JNJ5003 (50 mg/kg/day), during exposure to chronic stress. These studies suggest that FAAH is required for chronic stress to induce hyperactivity and structural remodeling of the amygdala. Collectively, these studies indicate that FAAH-mediated decreases in AEA occur following chronic stress and that this loss of AEA signaling is functionally relevant to the effects of chronic stress. These data support the hypothesis that inhibition of FAAH has therapeutic potential in the treatment of anxiety disorders, possibly by maintaining normal amygdalar function in the face of chronic stress. PMID:22776900

  17. Increasing human Th17 differentiation through activation of orphan nuclear receptor retinoid acid-related orphan receptor γ (RORγ) by a class of aryl amide compounds.

    PubMed

    Zhang, Wei; Zhang, Jing; Fang, Leiping; Zhou, Ling; Wang, Shuai; Xiang, Zhijun; Li, Yuan; Wisely, Bruce; Zhang, Guifeng; An, Gang; Wang, Yonghui; Leung, Stewart; Zhong, Zhong

    2012-10-01

    In a screen for small-molecule inhibitors of retinoid acid-related orphan receptor γ (RORγ), we fortuitously discovered that a class of aryl amide compounds behaved as functional activators of the interleukin 17 (IL-17) reporter in Jurkat cells. Three of these compounds were selected for further analysis and found to activate the IL-17 reporter with potencies of ∼0.1 μM measured by EC₅₀. These compounds were shown to directly bind to RORγ by circular dichroism-based thermal stability experiments. Furthermore, they can enhance an in vitro Th17 differentiation process in human primary T cells. As RORγ remains an orphan nuclear receptor, discovery of these aryl amide compounds as functional agonists will now provide pharmacological tools for us to dissect functions of RORγ and facilitate drug discovery efforts for immune-modulating therapies.

  18. Conformation-Specific IR and UV Spectroscopy of the Amino Acid Glutamine: Amide-Stacking and Hydrogen Bonding in AN Important Residue in Neurodegenerative Diseases

    NASA Astrophysics Data System (ADS)

    Walsh, Patrick S.; Dean, Jacob C.; Zwier, Timothy S.

    2014-06-01

    Glutamine plays an important role in several neurodegenerative diseases including Huntington's disease (HD) and Alzheimer's disease (AD). An intriguing aspect of the structure of glutamine is its incorporation of an amide group in its side chain, thereby opening up the possibility of forming amide-amide H-bonds between the peptide backbone and side chain. In this study the conformational preferences of two capped gluatamines Z(carboxybenzyl)-Glutamine-X (X=OH, NHMe) are studied under jet-cooled conditions in the gas phase in order to unlock the intrinsic structural motifs that are favored by this flexible sidechain. Conformational assignments are made by comparing the hydride stretch ( 3100-3700 cm-1) and amide I and II ( 1400-1800 cm-1) resonant ion-dip infrared spectra with predictions from harmonic frequency calculations. Assigned structures will be compared to previously published results on both natural and unnatural residues. Particular emphasis will be placed on the comparison between glutamine and unconstrained γ-peptides due to the similar three-carbon spacing between backbone and side chain in glutamine to the backbone spacing in γ-peptides. The ability of the glutamine side-chain to form amide stacked conformations will be a main focus, along with the prevalence of extended backbone type structures. W. H. James, III, C W. Müller, E. G. Buchanan, M. G. D. Nix, L. Guo, L. Roskop, M. S. Gordon, L. V. Slipchenko, S. H. Gellman, and T. S. Zwier, J. Am. Chem. Soc., 2009, 131(40), 14243-14245.

  19. Structures of D-amino-acid amidase complexed with L-phenylalanine and with L-phenylalanine amide: insight into the D-stereospecificity of D-amino-acid amidase from Ochrobactrum anthropi SV3.

    PubMed

    Okazaki, Seiji; Suzuki, Atsuo; Mizushima, Tsunehiro; Komeda, Hidenobu; Asano, Yasuhisa; Yamane, Takashi

    2008-03-01

    The crystal structures of D-amino-acid amidase (DAA) from Ochrobactrum anthropi SV3 in complex with L-phenylalanine and with L-phenylalanine amide were determined at 2.3 and 2.2 A resolution, respectively. Comparison of the L-phenylalanine amide complex with the D-phenylalanine complex reveals that the D-stereospecificity of DAA might be achieved as a consequence of three structural factors: (i) the hydrophobic cavity in the region in which the hydrophobic side chain of the substrate is held, (ii) the spatial arrangement of Gln310 O and Glu114 O epsilon2 that fixes the amino N atom of the substrate and (iii) the existence of two cavities that keep the carboxyl/amide group of the substrate near or apart from Ser60 O gamma.

  20. Zinc(II) complexes with heterocyclic ether, acid and amide. Crystal structure, spectral, thermal and antibacterial activity studies

    NASA Astrophysics Data System (ADS)

    Jabłońska-Wawrzycka, Agnieszka; Rogala, Patrycja; Czerwonka, Grzegorz; Hodorowicz, Maciej; Stadnicka, Katarzyna

    2016-02-01

    The reaction of zinc salts with heterocyclic ether (1-ethoxymethyl-2-methylimidazole (1-ExMe-2-MeIm)), acid (pyridine-2,3-dicarboxylic acid (2,3-pydcH2)) and amide (3,5-dimethylpyrazole-1-carboxamide (3,5-DMePzCONH2)) yielded three new zinc complexes formulated as [Zn(1-ExMe-2-MeIm)2Cl2] 1, fac-[Zn(H2O)6][Zn(2,3-pydcH)3]22 and [Zn(3,5-DMePz)2(NCO)2] 3. Complexes of 1 and 3 are four-coordinated with a tetrahedron as coordination polyhedron. However, compound 2 forms an octahedral cation-anion complex. The complex 3 was prepared by eliminating of the carboxamide group from the ligand and then the 3,5-dimethylpyrazole (3,5-DMePz) and isocyanates formed were employed as new ligands. The IR and X-ray studies have confirmed a bidentate fashion of coordination of the 2,3-pydcH and monodentate fashion of coordination of the 1-ExMe-2-MeIm and 3,5-DMePz to the Zn(II) ions. The crystal packing of Zn(II) complexes are stabilized by intermolecular classical hydrogen bonds of O-H⋯O and N-H⋯O types. The most interesting feature of the supramolecular architecture of complexes is the existence of C-H⋯O, C-H⋯Cl and C-H⋯π interactions and π⋯π stacking, which also contributes to structural stabilisation. The correlation between crystal structure and thermal stability of zinc complexes is observed. In all compounds the fragments of ligands donor-atom containing go in the last steps. Additionally, antimicrobial activities of compounds were carried out against certain Gram-positive and Gram-negative bacteria and counts of CFU (colony forming units) were also determined. The achieved results confirmed a significant antibacterial activity of some tested zinc complexes. On the basis of the Δ log CFU values the antibacterial activity of zinc complexes follows the order: 3 > 2 > 1. Influence a number of N-donor atoms in zinc environment on antibacterial activity is also observed.

  1. Fine-Tuning of Lewis Acidity: The Case of Borenium Hydride Complexes Derived from Bis(phosphinimino)amide Boron Precursors.

    PubMed

    Jaiswal, Kuldeep; Prashanth, Billa; Singh, Sanjay

    2016-07-25

    Reactions of bis(phosphinimino)amines LH and L'H with Me2 S⋅BH2 Cl afforded chloroborane complexes LBHCl (1) and L'BHCl (2), and the reaction of L'H with BH3 ⋅Me2 S gave a dihydridoborane complex L'BH2 (3) (LH=[{(2,4,6-Me3 C6 H2 N)P(Ph2 )}2 N]H and L'H=[{(2,6-iPr2 C6 H3 N)P(Ph2 )}2 N]H). Furthermore, abstraction of a hydride ion from L'BH2 (3) and LBH2 (4) mediated by Lewis acid B(C6 F5 )3 or the weakly coordinating ion pair [Ph3 C][B(C6 F5 )4 ] smoothly yielded a series of borenium hydride cations: [L'BH](+) [HB(C6 F5 )3 ](-) (5), [L'BH](+) [B(C6 F5 )4 ](-) (6), [LBH](+) [HB(C6 F5 )3 ](-) (7), and [LBH](+) [B(C6 F5 )4 ](-) (8). Synthesis of a chloroborenium species [LBCl](+) [BCl4 ](-) (9) without involvement of a weakly coordinating anion was also demonstrated from a reaction of LBH2 (4) with three equivalents of BCl3 . It is clear from this study that the sterically bulky strong donor bis(phosphinimino)amide ligand plays a crucial role in facilitating the synthesis and stabilization of these three-coordinated cationic species of boron. Therefore, the present synthetic approach is not dependent on the requirement of weakly coordinating anions; even simple BCl4 (-) can act as a counteranion with borenium cations. The high Lewis acidity of the boron atom in complex 8 enables the formation of an adduct with 4-dimethylaminopyridine (DMAP), [LBH⋅(DMAP)](+) [B(C6 F5 )4 ](-) (10). The solid-state structures of complexes 1, 5, and 9 were investigated by means of single-crystal X-ray structural analysis. PMID:27351275

  2. Caffeic acid phenethyl amide improves glucose homeostasis and attenuates the progression of vascular dysfunction in Streptozotocin-induced diabetic rats

    PubMed Central

    2013-01-01

    Background Glucose intolerance and cardiovascular complications are major symptoms in patients with diabetes. Many therapies have proven beneficial in treating diabetes in animals by protecting the cardiovascular system and increasing glucose utilization. In this study, we evaluated the effects of caffeic acid phenethyl amide (CAPA) on glucose homeostasis and vascular function in streptozotocin (STZ)-induced type 1 diabetic rats. Methods Diabetes (blood glucose levels > 350 mg/dL), was induced in Wistar rats by a single intravenous injection of 60 mg/kg STZ. Hypoglycemic effects were then assessed in normal and type 1 diabetic rats. In addition, coronary blood flow in Langendorff-perfused hearts was evaluated in the presence or absence of nitric oxide synthase (NOS) inhibitor. The thoracic aorta was used to measure vascular response to phenylephrine. Finally, the effect of chronic treatment of CAPA and insulin on coronary artery flow and vascular response to phenylephrine were analyzed in diabetic rats. Results Oral administration of 0.1 mg/kg CAPA decreased plasma glucose in normal (32.9 ± 2.3% decrease, P < 0.05) and diabetic rats (11.8 ± 5.5% decrease, P < 0.05). In normal and diabetic rat hearts, 1–10 μM CAPA increased coronary flow rate, and this increase was abolished by 10 μM NOS inhibitor. In the thoracic aorta, the concentration/response curve of phenylephrine was right-shifted by administration of 100 μM CAPA. Coronary flow rate was reduced to 7.2 ± 0.2 mL/min at 8 weeks after STZ-induction. However, 4 weeks of treatment with CAPA (3 mg/kg, intraperitoneal, twice daily) started at 4 weeks after STZ induction increased flow rate to 11.2 ± 0.5 mL/min (P < 0.05). In addition, the contractile response induced by 1 μM phenylephrine increased from 6.8 ± 0.6 mN to 11.4 ± 0.4 mN (P < 0.05) and 14.9 ± 1.4 mN (P < 0.05) by insulin (1 IU/kg, intraperitoneal) or CAPA treatment, respectively. Conclusions CAPA induced hypoglycemic activity, increased

  3. (E)-4-aryl-4-oxo-2-butenoic acid amides, chalcone–aroylacrylic acid chimeras: Design, antiproliferative activity and inhibition of tubulin polymerization

    PubMed Central

    Vitorović-Todorović, Maja D.; Erić-Nikolić, Aleksandra; Kolundžija, Branka; Hamel, Ernest; Ristić, Slavica; Juranić, Ivan O.; Drakulić, Branko J.

    2013-01-01

    Antiproliferative activity of twenty-nine (E)-4-aryl-4-oxo-2-butenoic acid amides against three human tumor cell lines (HeLa, FemX, and K562) is reported. Compounds showed antiproliferative activity in one-digit micromolar to submicromolar concentrations. The most active derivatives toward all the cell lines tested bear alkyl substituents on the aroyl moiety of the molecules. Fourteen compounds showed tubulin assembly inhibition at concentrations <20 μM. The most potent inhibitor of tubulin assembly was unsubstituted compound 1, with IC50 = 2.9 μM. Compound 23 had an oral LD50 in vivo of 45 mg/kg in mice. Cell cycle analysis on K562 cells showed that compounds 1, 2 and 23 caused accumulation of cells in the G2/M phase, but inhibition of microtubule polymerization is not the principal mode of action of the compounds. Nevertheless, they may be useful leads for the design of a new class of antitubulin agents. PMID:23353745

  4. Anandamide Externally Added to Lipid Vesicles Containing-Trapped Fatty Acid Amide Hydrolase (FAAH) Is Readily Hydrolyzed in a Sterol-Modulated Fashion

    PubMed Central

    2012-01-01

    We show that anandamide (AEA) externally added to model membrane vesicles containing trapped fatty acid amide hydrolyase (FAAH) can be readily hydrolyzed, demonstrating facile, rapid anandamide movement across the lipid bilayer. The rate of hydrolysis is significantly facilitated by cholesterol and coprostanol, but not by cholesterol sulfate. The effects of sterol upon hydrolysis by FAAH bound to the outer surface of the bilayer were much smaller, although they followed the same pattern. We propose the facilitation of hydrolysis is a combination of the effects of sterol on accessibility of membrane-inserted endocannabinoids to surface protein, and on the rate of endocannabinod transport across the membrane bilayer. PMID:22860204

  5. [Synthetic transformations of higher terpenoids. XXX. Synthesis and cytotoxic activity of betulonic acid amides with a piperidine or pyrrolidine nitroxide moiety].

    PubMed

    Antimonova, A N; Petrenko, N I; Shults, E E; Polienko, Iu F; Shakirov, M M; Irtegova, I G; Pokrovskiĭ, M A; Sherman, K M; Grigor'ev, I A; Pokrovskiĭ, A G; Tolstikov, G A

    2013-01-01

    The reaction of betulonic acid chloride with 4-amino-2,2,6,6-tetramethylpeperidine-1-oxyl, 3-amino-2,2,5,5-tetramethylpyrrolidine-1-oxyl and 3-aminomethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl gave corresponding triterpenoid amides. It was found that new derivatives exhibit cytotoxic activity against tumor cells CEM-13, U-937, MT-4. CCID50 value for most activity compound--N-[3-oxolup-20(29)-en-30-yl]-(2,2,6,6-tetramethylpiperidine-4-yl)-1-oxyl--was 5.7-33.1 microM.

  6. Synthesis and Structure-activity Relationship Studies of O-Biphenyl-3-yl Carbamates as Peripherally Restricted Fatty Acid Amide Hydrolase Inhibitors

    PubMed Central

    Moreno-Sanz, Guillermo; Duranti, Andrea; Melzig, Laurin; Fiorelli, Claudio; Ruda, Gian Filippo; Colombano, Giampiero; Mestichelli, Paola; Sanchini, Silvano; Tontini, Andrea; Mor, Marco; Bandiera, Tiziano; Scarpelli, Rita; Tarzia, Giorgio; Piomelli, Daniele

    2014-01-01

    The peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor URB937 (3, cyclohexylcarbamic acid 3’-carbamoyl-6-hydroxybiphenyl-3-yl ester) is extruded from the brain and spinal cord by the Abcg2 efflux transporter. Despite its inability to enter the central nervous system (CNS), 3 exerts profound antinociceptive effects in mice and rats, which result from the inhibition of FAAH in peripheral tissues and the consequent enhancement of anandamide signaling at CB1 cannabinoid receptors localized on sensory nerve endings. In the present study, we examined the structure-activity relationships (SAR) for the biphenyl region of compound 3, focusing on the carbamoyl and hydroxyl groups in the distal and proximal phenyl rings. Our SAR studies generated a new series of peripherally restricted FAAH inhibitors and identified compound 35 (cyclohexylcarbamic acid 3’-carbamoyl-5-hydroxybiphenyl-3-yl ester) as the most potent brain-impermeant FAAH inhibitor disclosed to date. PMID:23822179

  7. Transesterification and amide cis-trans isomerization in Zn and Cd complexes of the chelating amino acid ligand Boc-Asp(Dpa)-OBzl.

    PubMed

    Niklas, Nicole; Zahl, Achim; Alsfasser, Ralf

    2007-01-01

    The amino acid derivative Boc-Asp-OBzl (Boc=N-butyloxycarbonyl; Asp=aspartic acid; Bzl=benzyl) was functionalized by coupling its carboxylate side chain to dipicolylamine. This yielded the tridentate nitrogen donor ligand Boc-Asp(Dpa)-OBzl (-OBzl). The compound -OBzl contains three different carbonyl groups: a tertiary amide linkage between Asp and Dpa, a C-terminal benzyl ester function, and an N-terminal urethane protecting group. NMR spectra were used to compare the reactivity of these moieties. The Boc protecting group gives rise to two isomers, (E, 9%) and (Z, 91%). Coordination of Cd(NO3)2 and Zn(NO3)2 yielded the complexes and. These compounds have significantly reduced barriers to rotation about the tertiary amide C-N bond compared with the free ligand (-OBzl:18.5 kcal mol-1 in CDBr3;: 12.9 kcal mol-1 in (CD3)2CO;: 13.8 kcal mol-1 in (CD3)2CO). Both complexes readily undergo transesterification in methanol or CD3OD. Experimental pseudo-first order rate constants were determined in CD3OD and (CD3)2CO:CD3OD (3:1;). It was found that the zinc complex (k=(2.28+/-0.02)x10(-4) s-1) is significantly more reactive than the cadmium complex (k=(1.41+/-0.03)x10(-6) s-1). In order to study their tertiary amide cis-trans isomerization, the cadmium complex [(-OCH3)Cd(NO3)2] was synthesized, and the zinc complex [(-OCD3)Zn(NO3)2] was generated in situ in (CD3)2CO:CD3OD (3:1). The barriers to rotation were determined (:14.1 kcal mol-1 in CD3OD;: 13.4 kcal mol-1 in (CD3)2CO:CD3OD (3:1)). Our results show that the stronger Lewis-acid zinc(II) is significantly more active than cadmium(II) in the acceleration of the transesterification. This is in marked contrast to the tertiary amide bond rotation which is comparably fast with both metal ions. PMID:17160185

  8. Synthesis, insecticidal activities, and SAR studies of novel pyridylpyrazole acid derivatives based on amide bridge modification of anthranilic diamide insecticides.

    PubMed

    Wang, Bao-Lei; Zhu, Hong-Wei; Ma, Yi; Xiong, Li-Xia; Li, Yong-Qiang; Zhao, Yu; Zhang, Ji-Feng; Chen, You-Wei; Zhou, Sha; Li, Zheng-Ming

    2013-06-12

    Anthranilic diamides are one of the most important classes of modern agricultural insecticides. To discover new structure-modified compounds with high activity, series of novel carbonyl thioureas, carbonyl ureas, oxadiazoles, carbonyl thiophosphorylureas, oxadiazole-containing amides, and thiazoline-containing amides were designed through the modification of the amide bridge based on the structure of chlorantraniliprole and were synthesized, and bioassays were carried out. The compounds were characterized and confirmed by melting point, IR, (1)H NMR, and elemental analyses or HRMS. Preliminary bioassays indicated that some compounds exhibited significant insecticidal activities against oriental armyworm, diamondback moth, beet armyworm, corn borer, and mosquito. Among them, trifluoroethoxyl-containing carbonyl thiourea 20a showed best larvicidal activity against oriental armyworm, with LC50 and LC95 values of 0.1812 and 0.7767 mg/L, respectively. Meanwhile, 20c and 20e showed 86 and 57% death rates against diamondback moth at 0.005 mg/L, and the LC50 values of the two compounds were 0.0017 and 0.0023 mg/L, respectively, which were lower than that of the control chlorantraniliprole. The relationship between structure and insecticidal activity was discussed, and the HF calculation results indicated that the carbonyl thiourea moiety plays an important role in the insecticidal activity. The present work demonstrated that the trifluoroethoxyl-containing carbonyl thioureas can be used as lead compounds for further development of novel insecticides.

  9. Tris(2-aminoethyl)amine-based α-branched fatty acid amides - Synthesis of lipids and comparative study of transfection efficiency of their lipid formulations.

    PubMed

    Erdmann, Nicole; Wölk, Christian; Schulze, Ingo; Janich, Christopher; Folz, Manuela; Drescher, Simon; Dittrich, Matthias; Meister, Annette; Vogel, Jürgen; Groth, Thomas; Dobner, Bodo; Langner, Andreas

    2015-10-01

    The synthesis of a new class of cationic lipids, tris(2-aminoethyl)amine-based α-branched fatty acid amides, is described resulting in a series of lipids with specific variations in the lipophilic as well as the hydrophilic part of the lipids. In-vitro structure/transfection relationships were established by application of complexes of these lipids with plasmid DNA (pDNA) to different cell lines. The α-branched fatty acid amide bearing two tetradecyl chains and two lysine molecules (T14diLys) in mixture with the co-lipid 1,2-di-[(9Z)-octadec-9-enoyl]-sn-glycero-3-phosphoethanolamine (DOPE) (1/2, n/n) exhibits effective pDNA transfer in three different cell lines, namely Hep-G2, A549, and COS-7. The presence of 10% serum during lipoplex incubation of the cells did not affect the transfection efficiency. Based on that, detailed investigations of the complexation of pDNA with the lipid formulation T14diLys/DOPE 1/2 (n/n) were carried out with respect to particle size and charge using dynamic light scattering (DLS), ζ-potential measurements, and transmission electron microscopy (TEM). Additionally, the lipoplex uptake was investigated by confocal laser scanning microscopy (CLSM). Overall, lipoplexes prepared from T14diLys/DOPE 1/2 (n/n) offer large potential as lipid-based polynucleotide carriers and further justify advanced examinations.

  10. Supramolecular chirality in organo-, hydro-, and metallogels derived from bis-amides of L-(+)-tartaric acid: formation of highly aligned 1D silica fibers and evidence of 5-c net SnS topology in a metallogel network.

    PubMed

    Das, Uttam Kumar; Dastidar, Parthasarathi

    2012-10-01

    A series of bis-amides derived from L-(+)-tartaric acid was synthesized as potential low-molecular-weight gelators. Out of 14 bis-amides synthesized, 13 displayed organo-, hydro-, and ambidextrous gelation behavior. The gels were characterized by methods including circular dichroism, differential scanning calorimetry, optical and electron microscopy, and rheology. One of the gels derived from di-3-pyridyltartaramide (D-3-PyTA) displayed intriguing nanotubular morphology of the gel network, which was exploited as a template to generate highly aligned 1D silica fibers. The gelator D-3-PyTA was also exploited to generate metallogels by treatment with various Cu(II) /Zn(II) salts under suitable conditions. A structure-property correlation on the basis of single-crystal and powder X-ray diffraction data was attempted to gain insight into the structures of the gel networks in both organo- and metallogels. Such study led to the determination of the gel-network structure of the Cu(II) coordination-polymer-based metallogel, which displayed a 2D sheet architecture made of a chloride-bridged double helix that resembled a 5-c net SnS topology.

  11. Amino acid-functionalized multi-walled carbon nanotubes for improving compatibility with chiral poly(amide-ester-imide) containing L-phenylalanine and L-tyrosine linkages

    NASA Astrophysics Data System (ADS)

    Abdolmaleki, Amir; Mallakpour, Shadpour; Borandeh, Sedigheh

    2013-12-01

    Amino acid functionalized multi-walled carbon nanotubes (f-MWCNTs)/poly(amide-ester-imide) (PAEI) composites were fabricated by solution mixing method. Proper functionalization and mixing strategy of MWCNTs provides the best opportunity for better distribution and bonding of nanoparticles to the polymer matrix. MWCNTs have been chemically modified with L-phenylalanine to improve their compatibility with L-phenylalanine based PAEI. Field emission scanning electron microscopy micrographs of composite revealed that f-MWCNTs made a good interaction with polymer chains by wrapping the polymer around them, and transmission electron microscopy results confirmed well dispersion with nano size of f-MWCNTs in the polymer matrix. In addition, thermal analysis showed good enhancement in thermal properties of composites compared to pure polymer. Thermal stability of the composites containing f-MWCNTs was enhanced due to their good dispersion and improved interfacial interaction between the amino acid based PAEI matrix and f-MWCNTs.

  12. Extraterrestrial Amino Acids in Ureilites Including Almahata Sitta

    NASA Technical Reports Server (NTRS)

    Burton, A. S.; Glavin, D. P.; Callahan, M. P.; Dworkin, J. P.

    2011-01-01

    Ureilites are a class of meteorites that lack chondrules (achondrites) but have relatively high carbon abundances, averaging approx.3 wt %. Using highly sensitive liquid chromatography coupled with UV fluorescence and time-of-flight mass spectrometry (LC-FD/ToF-MS), it was recently determined that there are amino acids in. fragment 94 of the Almahata Sitta ureilite[l]. Based on the presence of amino acids that are rare in the Earth's biosphere, as well as the near-racemic enantiomeric ratios of marry of the more common amino acids, it was concluded that most of the detected amino acids were indigenous to the meteorite. Although the composition of the Almahata Sitta ureilite appears to be unlike other recovered ureilites, the discovery of amino acids in this meteorite raises the question of whether other ureilites rnav also contain amino acids. Herein we present the results of LC-FDlTo.F-MS analyses of: a sand sample from the Almahata Sitta strewn held, Almahata Sitta fragments 425 (an ordinary H5 chondrite) and 427 (ureilite), as well as an Antarctic ureilite (Allan lulls, ALHA 77257).

  13. Occurrence of N-phenylpropenoyl-L-amino acid amides in different herbal drugs and their influence on human keratinocytes, on human liver cells and on adhesion of Helicobacter pylori to the human stomach.

    PubMed

    Hensel, A; Deters, A M; Müller, G; Stark, T; Wittschier, N; Hofmann, T

    2007-02-01

    Thirty commonly used medicinal plants were screened by a selective and specific LC-MS/MS method for the occurrence of N-phenylpropenoyl- L-amino acid amides, a new homologous class of secondary products. In 15 plants, one or more of the respective derivatives (1 to 12) were found and quantitated. Especially roots from Angelica archangelica, fruits of Cassia angustifolia, C. senna, Coriandrum sativum, leaves from Hedera helix, flowers from Lavandula spec. and from Sambucus nigra contained high amounts (1 to 11 microg/g) of mixtures of the different amides 1 to 12. For functional investigations on potential activity in cellular physiology, two amides with an aliphatic (8) and an aromatic amino acid residue (5) were used. N-(E)-Caffeic acid L-aspartic acid amide (8) and N-(E)-caffeic acid L-tryptophan amide (5) stimulated mitochondrial activity as well as the proliferation rate of human liver cells (HepG2) at 10 microg/mL significantly. When monitoring the influence of selected phase I and II metabolizing enzymes, both compounds did not influence CYP3A4 gene expression, but stimulated CYP1A2 gene expression and inhibited GST expression. Also, the proliferation of human keratinocytes (NHK) was increased up to 150% by both amides 5 and 8; this stimulation was also detectable on the level of gene expression by an up-regulation of the transcription factor STAT6. The aliphatic aspartic compound 8 showed strong antiadhesive properties on the adhesion of Helicobacter pylori to human stomach tissue. PMID:17295182

  14. Collective vibrational effects in hydrogen bonded liquid amides and proteins studied by isotopic substitution

    NASA Astrophysics Data System (ADS)

    Nielsen, O. F.; Johansson, C.; Christensen, D. H.; Hvidt, S.; Flink, J.; Høime Hansen, S.; Poulsen, F.

    2000-09-01

    Raman spectroscopy is used to study the fast dynamics of simple liquid amides and proteins. Raman spectra in the visible region of liquid amides are obtained with a triple additive scanning monochromator, whereas FT-Raman technique is used in the near-IR region in order to avoid fluorescence from impurities in the proteins. Raman spectra are shown in the amide-I region of HCONHCH 3 ( N-methylformamide with all isotopes in their natural abundance), H 13CONHCH 3, HC 18ONHCH 3, human growth hormone, frog tropomyosin and chymotrypsin inhibitor 2 including C-13 and N-15 enriched samples of the latter. Resonance energy transfer (RET) between amide molecules gives rise to a non-coincidence effect of the anisotropic and the isotropic components of the amide-I band. This effect influences the band position in mixtures of liquid amide isotopomers. A further spectral feature caused by collective vibrational modes in the hydrogen bonded liquid amides is named coalescence of bands in mixtures of isotopomers (CBMI). The result of this effect is that only one band is found in mixtures of isotopomers where bands at different frequencies are observed for each of the isotopomers. A similar effect may account for the observation of protein amide-I bands with frequencies dependent only on the secondary structure of the protein and not on the amino acid residues. RET and CBMI are due to a collectivity of vibrational modes in different amide molecules. This collectivity may be related to a cooperativity of hydrogen bonds. A low-frequency band around 100 cm -1 is observed in hydrogen bonded liquid amides and proteins. Isotopic substitution shows that the mode corresponding to this band involves displacements of atoms in hydrogen bonds. This mode may drive a breaking of the hydrogen bond.

  15. Antiradical activity of gallic acid included in lipid interphases.

    PubMed

    Salcedo, C L; Frías, M A; Cutro, A C; Nazareno, M A; Disalvo, E A

    2014-10-01

    Polyphenols are well known as antioxidant agents and by their effects on the hydration layers of lipid interphases. Among them, gallic acid and its derivatives are able to decrease the dipole potential and to act in water as a strong antioxidant. In this work we have studied both effects on lipid interphases in monolayers and bilayers of dimyristoylphosphatidylcholine. The results show that gallic acid (GA) increases the negative surface charges of large unilamellar vesicles (LUVs) and decreases the dipole potential of the lipid interphase. As a result, positively charged radical species such as ABTS(+) are able to penetrate the membrane forming an association with GA. These results allow discussing the antiradical activity (ARA) of GA at the membrane phase which may be taking place in water spaces between the lipids.

  16. Synthesis of amphiphilic poly(ether-amide) dendrimer endcapped with poly(ethylene glycol) grafts and its solubilization to salicylic acid.

    PubMed

    Yang, Zhu; Zhang, Wenquan; Liu, Jianhua; Shi, Wenfang

    2007-04-01

    An amphiphilic dendrimer (DPEA-PEG) grafting polyethylene glycol at the terminals was prepared by endcapping of dendritic poly(ether-amide) (DPEA) with isocyanate terminated linear polyethylene glycol (PEG-NCO). The molecular structure was verified by gel permeation chromatography (GPC), (1)H NMR and FT-IR. The micelle characteristic of DPEA-PEG in water was investigated. The critical micelle concentration (CMC) was determined by a fluorescence technique to be 55.5 mg/L. The hydrodynamic radius of micelles was measured by dynamic light scattering (DLS) to be 76.2 nm. The UV-vis spectrum showed that the solubility of salicylic acid increased from 1.91 to 2.78 mg/L when the concentration of DPEA-PEG attained 5 mg/mL in an aqueous solution.

  17. Reactivity of a Nickel(II) Bis(amidate) Complex with meta-Chloroperbenzoic Acid: Formation of a Potent Oxidizing Species.

    PubMed

    Corona, Teresa; Pfaff, Florian F; Acuña-Parés, Ferran; Draksharapu, Apparao; Whiteoak, Christopher J; Martin-Diaconescu, Vlad; Lloret-Fillol, Julio; Browne, Wesley R; Ray, Kallol; Company, Anna

    2015-10-12

    Herein, we report the formation of a highly reactive nickel-oxygen species that has been trapped following reaction of a Ni(II) precursor bearing a macrocyclic bis(amidate) ligand with meta-chloroperbenzoic acid (HmCPBA). This compound is only detectable at temperatures below 250 K and is much more reactive toward organic substrates (i.e., C-H bonds, C=C bonds, and sulfides) than previously reported well-defined nickel-oxygen species. Remarkably, this species is formed by heterolytic O-O bond cleavage of a Ni-HmCPBA precursor, which is concluded from experimental and computational data. On the basis of spectroscopy and DFT calculations, this reactive species is proposed to be a Ni(III) -oxyl compound.

  18. Reactivity of a Nickel(II) Bis(amidate) Complex with meta-Chloroperbenzoic Acid: Formation of a Potent Oxidizing Species.

    PubMed

    Corona, Teresa; Pfaff, Florian F; Acuña-Parés, Ferran; Draksharapu, Apparao; Whiteoak, Christopher J; Martin-Diaconescu, Vlad; Lloret-Fillol, Julio; Browne, Wesley R; Ray, Kallol; Company, Anna

    2015-10-12

    Herein, we report the formation of a highly reactive nickel-oxygen species that has been trapped following reaction of a Ni(II) precursor bearing a macrocyclic bis(amidate) ligand with meta-chloroperbenzoic acid (HmCPBA). This compound is only detectable at temperatures below 250 K and is much more reactive toward organic substrates (i.e., C-H bonds, C=C bonds, and sulfides) than previously reported well-defined nickel-oxygen species. Remarkably, this species is formed by heterolytic O-O bond cleavage of a Ni-HmCPBA precursor, which is concluded from experimental and computational data. On the basis of spectroscopy and DFT calculations, this reactive species is proposed to be a Ni(III) -oxyl compound. PMID:26311073

  19. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage

    PubMed Central

    Sasso, Oscar; Migliore, Marco; Habrant, Damien; Armirotti, Andrea; Albani, Clara; Summa, Maria; Moreno-Sanz, Guillermo; Scarpelli, Rita; Piomelli, Daniele

    2015-01-01

    The ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit cyclooxygenase (Cox)-1 and Cox-2 underlies the therapeutic efficacy of these drugs, as well as their propensity to damage the gastrointestinal (GI) epithelium. This toxic action greatly limits the use of NSAIDs in inflammatory bowel disease (IBD) and other chronic pathologies. Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide, which attenuates inflammation and promotes GI healing. Here, we describe the first class of systemically active agents that simultaneously inhibit FAAH, Cox-1, and Cox-2 with high potency and selectivity. The class prototype 4 (ARN2508) is potent at inhibiting FAAH, Cox-1, and Cox-2 (median inhibitory concentration: FAAH, 0.031 ± 0.002 µM; Cox-1, 0.012 ± 0.002 µM; and Cox-2, 0.43 ± 0.025 µM) but does not significantly interact with a panel of >100 off targets. After oral administration in mice, ARN2508 engages its intended targets and exerts profound therapeutic effects in models of intestinal inflammation. Unlike NSAIDs, ARN2508 causes no gastric damage and indeed protects the GI from NSAID-induced damage through a mechanism that requires FAAH inhibition. Multitarget FAAH/Cox blockade may provide a transformative approach to IBD and other pathologies in which FAAH and Cox are overactive.—Sasso, O., Migliore, M., Habrant, D., Armirotti, A., Albani, C., Summa, M., Moreno-Sanz, G., Scarpelli, R., Piomelli, D. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage. PMID:25757568

  20. Catalytic synthesis of amides via aldoximes rearrangement.

    PubMed

    Crochet, Pascale; Cadierno, Victorio

    2015-02-14

    Amide bond formation reactions are among the most important transformations in organic chemistry because of the widespread occurrence of amides in pharmaceuticals, natural products and biologically active compounds. The Beckmann rearrangement is a well-known method to generate secondary amides from ketoximes. However, under the acidic conditions commonly employed, aldoximes RHC=NOH rarely rearrange into the corresponding primary amides RC(=O)NH2. In recent years, it was demonstrated that this atom-economical transformation can be carried out efficiently and selectively with the help of metal catalysts. Several homogeneous and heterogenous systems have been described. In addition, protocols offering the option to generate the aldoximes in situ from the corresponding aldehydes and hydroxylamine, or even from alcohols, have also been developed, as well as a series of tandem processes allowing the access to N-substituted amide products. In this Feature article a comprehensive overview of the advances achieved in this particular research area is presented.

  1. Redox regulation of protein tyrosine phosphatase 1B (PTP1B): Importance of steric and electronic effects on the unusual cyclization of the sulfenic acid intermediate to a sulfenyl amide

    NASA Astrophysics Data System (ADS)

    Sarma, Bani Kanta

    2013-09-01

    The redox regulation of protein tyrosine phosphatase 1B (PTP1B) via the unusual transformation of its sulfenic acid (PTP1B-SOH) to a cyclic sulfenyl amide intermediate is studied by using small molecule chemical models. These studies suggest that the sulfenic acids derived from the H2O2-mediated reactions o-amido thiophenols do not efficiently cyclize to sulfenyl amides and the sulfenic acids produced in situ can be trapped by using methyl iodide. Theoretical calculations suggest that the most stable conformer of such sulfenic acids are stabilized by nO → σ*S-OH orbital interactions, which force the -OH group to adopt a position trans to the S⋯O interaction, leading to an almost linear arrangement of the O⋯S-O moiety and this may be the reason for the slow cyclization of such sulfenic acids to their corresponding sulfenyl amides. On the other hand, additional substituents at the 6-position of o-amido phenylsulfenic acids that can induce steric environment and alter the electronic properties around the sulfenic acid moiety by S⋯N or S⋯O nonbonded interactions destabilize the sulfenic acids by inducing strain in the molecule. This may lead to efficient the cyclization of such sulfenic acids. This model study suggests that the amino acid residues in the close proximity of the sulfenic acid moiety in PTP1B may play an important role in the cyclization of PTP1B-SOH to produce the corresponding sulfenyl amide.

  2. A New Derivative of Valproic Acid Amide Possesses a Broad-spectrum Antiseizure Profile and Unique Activity Against Status Epilepticus and Organophosphate Neuronal Damage

    PubMed Central

    White, H. Steve; Alex, Anitha B.; Pollock, Amanda; Hen, Naama; Shekh-Ahmad, Tawfeeq; Wilcox, Karen S.; McDonough, John H.; Stables, James P.; Kaufmann, Dan; Yagen, Boris; Bialer, Meir

    2011-01-01

    Summary Purpose sec-Butyl-propylacetamide (SPD) is a one-carbon homologue of valnoctamide (VCD), a CNS-active amide derivative of valproic acid (VPA) currently in phase II clinical trials. The current study evaluated the anticonvulsant activity of SPD in a battery of rodent seizure and epilepsy models and assessed its efficacy in rat and guinea pig models of status epilepticus (SE) and neuroprotection in an organotypic hippocampal slice model of excitotoxic cell death. Methods SPD’s anticonvulsant activity was evaluated in several rodent seizure and epilepsy models including: maximal electroshock (MES), 6Hz psychomotor, subcutaneous (s.c.) metrazol-, s.c., picrotoxin, s.c. bicuculline, audiogenic and corneal and hippocampal kindled seizures following intraperitoneal administration. Results obtained with SPD are discussed in relationship to those obtained with VPA and VCD. SPD was also evaluated for its ability to block benzodiazepine-resistant SE induced by pilocarpine (rats) and soman (rats and guinea pigs) following intraperitoneal administration. SPD was tested for its ability to block excitotoxic cell death induced by the glutamate agonists N-methyl-D-Aspartate (NMDA) and kainic acid (KA) using organotypic hippocampal slices and SE-induced hippocampal cell death using FluoroJade B staining. The cognitive function of SPD-treated rats that were protected against pilocarpine-induced convulsive SE was examined 10-14 days post SE using the Morris water maze (MWM). The relationship between the pharmacokinetic profile of SPD and its efficacy against soman-induced SE was evaluated in two parallel studies following SPD (60 mg/kg, i.p.) administration in the soman SE rat model. Key Findings SPD was highly effective and displayed a wide protective index (PI=TD50/ED50) in the standardized seizure and epilepsy models employed. SPD’s wide PI values demonstrate that it is effective at doses well below those that produce behavioral impairment. Unlike VCD, SPD also

  3. T. thermophila group I introns that cleave amide bonds

    NASA Technical Reports Server (NTRS)

    Joyce, Gerald F. (Inventor)

    1997-01-01

    The present invention relates to nucleic acid enzymes or enzymatic RNA molecules that are capable of cleaving a variety of bonds, including phosphodiester bonds and amide bonds, in a variety of substrates. Thus, the disclosed enzymatic RNA molecules are capable of functioning as nucleases and/or peptidases. The present invention also relates to compositions containing the disclosed enzymatic RNA molecule and to methods of making, selecting, and using such enzymes and compositions.

  4. Effect of propane-2-sulfonic acid octadec-9-enyl-amide on the expression of adhesion molecules in human umbilical vein endothelial cells.

    PubMed

    Chen, Cai-Xia; Yang, Li-Chao; Xu, Xu-Dong; Wei, Xiao; Gai, Ya-Ting; Peng, Lu; Guo, Han; Hao-Zhou; Wang, Yi-Qing; Jin, Xin

    2015-06-01

    Oleoylethanolamide (OEA), an endogenous agonist of PPARα, has been reported to have anti-atherosclerotic properties. However, OEA can be enzymatically hydrolyzed to oleic acid and ethanolamine and, thus, is not expected to be orally active. In the present study, we designed and synthesized an OEA analog, propane-2-sulfonic acid octadec-9-enyl-amide (N15), which is resistant to enzymatic hydrolysis. The purpose of this study was to investigate the effects of N15 on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results showed that N15 inhibited TNFα-induced production of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and the adhesion of monocytes to TNFα-induced HUVECs. Furthermore, the protective effect of N15 on inflammation is dependent upon a PPAR-α/γ-mediated mechanism. In conclusion, N15 protects against TNFα-induced vascular endothelial inflammation. This anti-inflammatory effect of N15 is dependent on PPAR-α/γ dual targets.

  5. Experimental colitis in mice is attenuated by changes in the levels of endocannabinoid metabolites induced by selective inhibition of fatty acid amide hydrolase (FAAH)

    PubMed Central

    Sałaga, M; Mokrowiecka, A; Zakrzewski, P K; Cygankiewicz, A; Leishman, E; Sobczak, M; Zatorski, H; Małecka-Panas, E; Kordek, R; Storr, M; Krajewska, W M; Bradshaw, H B; Fichna, J

    2014-01-01

    Background and aims Pharmacological treatment and/or maintenance of remission in inflammatory bowel diseases (IBD) is currently one of the biggest challenge in the field of gastroenterology. Available therapies are mostly limited to overcoming the symptoms, but not the cause of the disease. Recently, the endocannabinoid system has been proposed as a novel target in the treatment of IBD. Here we aimed to assess the anti-inflammatory action of the novel fatty acid amide hydrolase (FAAH) inhibitor PF-3845 and its effect on the endocannabinoid and related lipid metabolism during the course of experimental colitis. Methods We used two models of experimental colitis in mice (TNBS- and DSS-induced) and additionally, we employed LC/MS/MS spectrometry to determine the changes in biolipid levels in the mouse colon during inflammation. Results We showed that the FAAH inhibitor PF-3845 reduced experimental TNBS-induced colitis in mice and its anti-inflammatory action is associated with altering the levels of selected biolipids (arachidonic and oleic acid derivatives, prostaglandins and biolipids containing glycine in the mouse colon). Conclusions We show that FAAH is a promising pharmacological target and the FAAH-dependent biolipids play a major role in colitis. Our results highlight and promote therapeutic strategy based on targeting FAAH-dependent metabolic pathways in order to alleviate intestinal inflammation. PMID:24530133

  6. Enantioselective synthesis of α-oxy amides via Umpolung amide synthesis.

    PubMed

    Leighty, Matthew W; Shen, Bo; Johnston, Jeffrey N

    2012-09-19

    α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids. PMID:22967461

  7. RNA Bound to a Solid Phase can Select an Amino Acid and Facilitate Subsequent Amide Bond Formation

    NASA Astrophysics Data System (ADS)

    Mellersh, Anthony; Wilkinson, Alan-Shaun

    2000-01-01

    Polyadenylic acid (Poly A) immobilised on silica gel stereoselectively binds L-lysine from dilute aqueous solution. When the resulting complex is suspended in an organic solvent and liquid ammonia added, lysinamide is formed.

  8. Formation of amides, their intramolecular reactions for the synthesis of N-heterocycles, and preparation of a marketed drug, sildenafil: a comprehensive coverage.

    PubMed

    Laha, Joydev K; Patel, Ketul V; Tummalapalli, K S Satyanarayana; Dayal, Neetu

    2016-08-11

    A unified approach to the tandem preparation of diverse nitrogen heterocycles via decarboxylative acylation of ortho-substituted amines with α-oxocarboxylic acids and subsequent intramolecular cyclizations has been developed. The key features of this work include: the first example of transition-metal-free decarboxylative amidation of α-oxocarboxylic acids with ortho-substituted amines, realization of intramolecular cyclization of amides employing nucleophiles that have previously been unexplored, mechanistic investigation of an unprecedented K2S2O8 promoted amide formation and its subsequent intramolecular cyclizations, and application to the synthesis of a best-selling marketed drug. PMID:27430326

  9. Copoly(imide-amides) containing hexafluoroisopropylidene

    NASA Technical Reports Server (NTRS)

    Irvin, David J.; Cassidy, Patrick E.; Cameron, Mitch L.

    1990-01-01

    The incorporation of the hexafluoroisopropylidene (HFIP or 6F) group into polymer backbones brings about important and useful changes in properties. These differences include increased thermal and environmental resistance and solubility and decreased dielectric constant and color. Several types of backbones have been substrates for the inclusion of HFIP and all results have reflected impressive property benefits. This project involved the incorporation of 6F groups into a poly(imide-amide) backbone by the condensation of a 6F-containing dianhydride with 4-aminobenzoic acid to yield a diimide terminated with two carboxylic acid groups. This diacid trimer was then polymerized with various diamines. The polymers were obtained in yields of 86-94 percent and with viscosities of 0.90-2.26 dL/g. They were stable to above 500 C and clear, colorless films could be cast from DMAc.

  10. Characterisation of (R)-2-(2-Fluorobiphenyl-4-yl)-N-(3-Methylpyridin-2-yl)Propanamide as a Dual Fatty Acid Amide Hydrolase: Cyclooxygenase Inhibitor

    PubMed Central

    Gouveia-Figueira, Sandra; Karlsson, Jessica; Deplano, Alessandro; Hashemian, Sanaz; Svensson, Mona; Fredriksson Sundbom, Marcus; Congiu, Cenzo; Onnis, Valentina; Fowler, Christopher J.

    2015-01-01

    Background Increased endocannabinoid tonus by dual-action fatty acid amide hydrolase (FAAH) and substrate selective cyclooxygenase (COX-2) inhibitors is a promising approach for pain-relief. One such compound with this profile is 2-(2-fluorobiphenyl-4-yl)-N-(3-methylpyridin-2-yl)propanamide (Flu-AM1). These activities are shown by Flu-AM1 racemate, but it is not known whether its two single enantiomers behave differently, as is the case towards COX-2 for the parent flurbiprofen enantiomers. Further, the effects of the compound upon COX-2-derived lipids in intact cells are not known. Methodology/Principal Findings COX inhibition was determined using an oxygraphic method with arachidonic acid and 2-arachidonoylglycerol (2-AG) as substrates. FAAH was assayed in mouse brain homogenates using anandamide (AEA) as substrate. Lipidomic analysis was conducted in unstimulated and lipopolysaccharide + interferon γ- stimulated RAW 264.7 macrophage cells. Both enantiomers inhibited COX-2 in a substrate-selective and time-dependent manner, with IC50 values in the absence of a preincubation phase of: (R)-Flu-AM1, COX-1 (arachidonic acid) 6 μM; COX-2 (arachidonic acid) 20 μM; COX-2 (2-AG) 1 μM; (S)-Flu-AM1, COX-1 (arachidonic acid) 3 μM; COX-2 (arachidonic acid) 10 μM; COX-2 (2-AG) 0.7 μM. The compounds showed no enantiomeric selectivity in their FAAH inhibitory properties. (R)-Flu-AM1 (10 μM) greatly inhibited the production of prostaglandin D2 and E2 in both unstimulated and lipopolysaccharide + interferon γ- stimulated RAW 264.7 macrophage cells. Levels of 2-AG were not affected either by (R)-Flu-AM1 or by 10 μM flurbiprofen, either alone or in combination with the FAAH inhibitor URB597 (1 μM). Conclusions/Significance Both enantiomers of Flu-AM1 are more potent inhibitors of 2-AG compared to arachidonic acid oxygenation by COX-2. Inhibition of COX in lipopolysaccharide + interferon γ- stimulated RAW 264.7 cells is insufficient to affect 2-AG levels despite the

  11. A 2:1 co-crystal of p-nitro­benzoic acid and N,N′-bis­(pyridin-3-ylmeth­yl)ethanedi­amide: crystal structure and Hirshfeld surface analysis

    PubMed Central

    Syed, Sabrina; Halim, Siti Nadiah Abdul; Jotani, Mukesh M.; Tiekink, Edward R. T.

    2016-01-01

    The title 2:1 co-crystal, 2C7H5NO4·C14H14N4O2, in which the complete di­amide mol­ecule is generated by crystallographic inversion symmetry, features a three-mol­ecule aggregate sustained by hydroxyl-O—H⋯N(pyrid­yl) hydrogen bonds. The p-nitro­benzoic acid mol­ecule is non-planar, exhibiting twists of both the carb­oxy­lic acid and nitro groups, which form dihedral angles of 10.16 (9) and 4.24 (4)°, respectively, with the benzene ring. The di­amide mol­ecule has a conformation approximating to a Z shape, with the pyridyl rings lying to either side of the central, almost planar di­amide residue (r.m.s. deviation of the eight atoms being 0.025 Å), and forming dihedral angles of 77.22 (6)° with it. In the crystal, three-mol­ecule aggregates are linked into a linear supra­molecular ladder sustained by amide-N—H⋯O(nitro) hydrogen bonds and orientated along [10-4]. The ladders are connected into a double layer via pyridyl- and benzene-C—H⋯O(amide) inter­actions, which, in turn, are connected into a three-dimensional architecture via π–π stacking inter­actions between pyridyl and benzene rings [inter-centroid distance = 3.6947 (8) Å]. An evaluation of the Hirshfeld surfaces confirm the importance of inter­molecular inter­actions involving oxygen atoms as well as the π–π inter­actions. PMID:26870591

  12. A 2:1 co-crystal of p-nitro-benzoic acid and N,N'-bis-(pyridin-3-ylmeth-yl)ethanedi-amide: crystal structure and Hirshfeld surface analysis.

    PubMed

    Syed, Sabrina; Halim, Siti Nadiah Abdul; Jotani, Mukesh M; Tiekink, Edward R T

    2016-01-01

    The title 2:1 co-crystal, 2C7H5NO4·C14H14N4O2, in which the complete di-amide mol-ecule is generated by crystallographic inversion symmetry, features a three-mol-ecule aggregate sustained by hydroxyl-O-H⋯N(pyrid-yl) hydrogen bonds. The p-nitro-benzoic acid mol-ecule is non-planar, exhibiting twists of both the carb-oxy-lic acid and nitro groups, which form dihedral angles of 10.16 (9) and 4.24 (4)°, respectively, with the benzene ring. The di-amide mol-ecule has a conformation approximating to a Z shape, with the pyridyl rings lying to either side of the central, almost planar di-amide residue (r.m.s. deviation of the eight atoms being 0.025 Å), and forming dihedral angles of 77.22 (6)° with it. In the crystal, three-mol-ecule aggregates are linked into a linear supra-molecular ladder sustained by amide-N-H⋯O(nitro) hydrogen bonds and orientated along [10-4]. The ladders are connected into a double layer via pyridyl- and benzene-C-H⋯O(amide) inter-actions, which, in turn, are connected into a three-dimensional architecture via π-π stacking inter-actions between pyridyl and benzene rings [inter-centroid distance = 3.6947 (8) Å]. An evaluation of the Hirshfeld surfaces confirm the importance of inter-molecular inter-actions involving oxygen atoms as well as the π-π inter-actions. PMID:26870591

  13. Barriers to rotation adjacent to double bonds. 3. The C-O barrier in formic acid, methyl formate, acetic acid, and methyl acetate. The origin of ester and amide resonance

    SciTech Connect

    Wiberg, K.B.; Laidig, K.E.

    1987-09-30

    The structures of the rotamers about the C-O bonds of formic acid, methyl formate, acetic acid, and methyl acetate were calculated by using the 6-31G* basis set and complete geometrical relaxation. Large basis sets (6-311+G**) and correction for electron correlation were needed in order to obtain calculated barriers that were in good agreement with the available experimental data. The factors that control the geometry at a carbonyl group are considered, and it is shown that an analysis in terms of bond path angles leads to a direct connection with electronegativity. The nature of the interaction between an amino group and a carbonyl, as in an amide, is examined and shown not to involve charge transfer from the nitrogen to the carbonyl oxygen, but rather it involves charge transfer between carbon and nitrogen. The origin of the rotational barrier in esters and of the difference in energy between the E and Z conformers is discussed.

  14. Arachidonoyl ethanolamide (AEA)-induced Apoptosis is Mediated by J-series Prostaglandins and is Enhanced by Fatty Acid Amide Hydrolase (FAAH) Blockade

    PubMed Central

    Kuc, Christian; Jenkins, Audrey; Van Dross, R. T.

    2011-01-01

    The endocannabinoid arachidonoyl ethanolamide (AEA) is a potent inducer of tumor cell apoptosis however its mechanism of cytotoxicity is unclear. A previous report from our laboratory showed that AEA induced cell death in a COX-2-dependent manner and in this report our data indicate that AEA-induced apoptosis is mediated by COX-2 metabolic products of the J-series. In experiments conducted with JWF2 keratinocytes which overexpress COX-2, AEA caused a concentration-regulated increase in J-series prostaglandin production and apoptosis. Similarly, cell treatment with exogenously added J-series prostaglandins (15-deoxy, Δ12,14 PGJ2 and PGJ2) induced apoptosis. AEA-induced apoptosis was inhibited by the antioxidant, N-acetyl cysteine, indicating that reactive oxygen species generation was required for apoptosis. Using antagonists of cannabinoid receptor 1, cannabinoid receptor 2, or TRPV1, it was observed that cannabinoid receptor inhibition did not block AEA-mediated cell death. In contrast, an inhibitor of fatty acid amide hydrolase (FAAH) potentiated AEA-induced J-series PG synthesis and apoptosis. These results suggest that the metabolism of AEA to J-series PGs regulates the induction of apoptosis in cells with elevated COX-2 levels. Our data further indicate that the proapoptotic activity of AEA can be enhanced by combining it with an inhibitor of FAAH. As such, AEA may be an effective agent to eliminate tumor cells that overexpress COX-2. PMID:21432910

  15. The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1

    PubMed Central

    Fowler, CJ; Naidu, PS; Lichtman, A; Onnis, V

    2009-01-01

    Although the dominant approach to drug development is the design of compounds selective for a given target, compounds targeting more than one biological process may have superior efficacy, or alternatively a better safety profile than standard selective compounds. Here, this possibility has been explored with respect to the endocannabinoid system and pain. Compounds inhibiting the enzyme fatty acid amide hydrolase (FAAH), by increasing local endocannabinoid tone, produce potentially useful effects in models of inflammatory and possibly neuropathic pain. Local increases in levels of the endocannabinoid anandamide potentiate the actions of cyclooxygenase inhibitors, raising the possibility that compounds inhibiting both FAAH and cyclooxygenase can be as effective as non-steroidal anti-inflammatory drugs but with a reduced cyclooxygenase inhibitory ‘load’. An ibuprofen analogue active in models of visceral pain and with FAAH and cyclooxygenase inhibitory properties has been identified. Another approach, built in to the experimental analgesic compound N-arachidonoylserotonin, is the combination of FAAH inhibitory and transient receptor potential vanilloid type 1 antagonist properties. Although finding the right balance of actions upon the two targets is a key to success, it is hoped that dual-action compounds of the types illustrated in this review will prove to be useful analgesic drugs. PMID:19226258

  16. Self-reinforcement and hydrolytic degradation of amorphous lactic acid based poly(ester-amide), and of its composite with sol-gel derived fibers.

    PubMed

    Haltia, Anna-Maija; Lähteenkorva, Kimmo; Törmälä, Pertti; Helminen, Antti; Tuominen, Jukka; Seppälä, Jukka; Veittola, Sinikka; Ahvenlammi, Jarno

    2002-10-01

    The self-reinforcing and hydrolytic degradation of an amorphous poly(ester-amide) (PEA) based on lactic acid have been studied and compared with those of poly-L-lactide (PLLA). The studied PEA-rods were self-reinforced (SR) by solid-state die drawing resulting double shear strength. The hydrolytic degradation of PEA was studied during exposure to phosphate buffered saline at pH 7.4 and at 37 degrees C for 18 weeks. The degradation and mechanical properties of PEA were also followed in a self-reinforced composite structure consisting of PEA and sol-gel derived SiO(2)-fibers (SGF, 8 wt %). The hydrolytic degradation of the SR-PEA-rods with and without SG-fibers was significantly faster than that of SR-PLLA-rods. The weight average molecular weight (Mw) of PEA decreased by 90% from the initial Mw during the first 6 weeks in hydrolysis, when the Mw of the PLLA decreased by 10%. PMID:15348182

  17. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage.

    PubMed

    Sasso, Oscar; Migliore, Marco; Habrant, Damien; Armirotti, Andrea; Albani, Clara; Summa, Maria; Moreno-Sanz, Guillermo; Scarpelli, Rita; Piomelli, Daniele

    2015-06-01

    The ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit cyclooxygenase (Cox)-1 and Cox-2 underlies the therapeutic efficacy of these drugs, as well as their propensity to damage the gastrointestinal (GI) epithelium. This toxic action greatly limits the use of NSAIDs in inflammatory bowel disease (IBD) and other chronic pathologies. Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide, which attenuates inflammation and promotes GI healing. Here, we describe the first class of systemically active agents that simultaneously inhibit FAAH, Cox-1, and Cox-2 with high potency and selectivity. The class prototype 4: (ARN2508) is potent at inhibiting FAAH, Cox-1, and Cox-2 (median inhibitory concentration: FAAH, 0.031 ± 0.002 µM; Cox-1, 0.012 ± 0.002 µM; and Cox-2, 0.43 ± 0.025 µM) but does not significantly interact with a panel of >100 off targets. After oral administration in mice, ARN2508 engages its intended targets and exerts profound therapeutic effects in models of intestinal inflammation. Unlike NSAIDs, ARN2508 causes no gastric damage and indeed protects the GI from NSAID-induced damage through a mechanism that requires FAAH inhibition. Multitarget FAAH/Cox blockade may provide a transformative approach to IBD and other pathologies in which FAAH and Cox are overactive.

  18. Pharmacodynamic and pharmacokinetic analysis of CNS-active constitutional isomers of valnoctamide and sec-butylpropylacetamide--Amide derivatives of valproic acid.

    PubMed

    Mawasi, Hafiz; Shekh-Ahmad, Tawfeeq; Finnell, Richard H; Wlodarczyk, Bogdan J; Bialer, Meir

    2015-05-01

    Valnoctamide (VCD) and sec-butylpropylacetamide (SPD) are CNS-active closely related amide derivatives of valproic acid with unique anticonvulsant activity. This study evaluated how small chemical changes affect the pharmacodynamics (PD; anticonvulsant activity and teratogenicity) and pharmacokinetics (PK) of three constitutional isomers of SPD [sec-butylisopropylacetamide (SID) and tert-butylisopropylacetamide (TID)] and of VCD [tert-butylethylacetamide (TED)]. The anticonvulsant activity of SID, TID, and TED was comparatively evaluated in several rodent anticonvulsant models. The PK-PD relationship of SID, TID, and TED was evaluated in rats, and their teratogenicity was evaluated in a mouse strain highly susceptible to teratogen-induced neural tube defects (NTDs). sec-Butylisopropylacetamide and TID have a similar PK profile to SPD which may contribute to their similar anticonvulsant activity. tert-Butylethylacetamide had a better PK profile than VCD (and SPD); however, this did not lead to a superior anticonvulsant activity. sec-Butylisopropylacetamide and TED did not cause NTDs at doses 4-7 times higher than their anticonvulsant ED50 values. In rats, SID, TID (ip), and TED exhibited a broad spectrum of anticonvulsant activity. However, combined anticonvulsant analysis in mice and rats shows SID as the most potent compound with similar activity to that of SPD, demonstrating that substitution of the isobutyl moiety in the SPD or VCD molecule by tert-butyl as well as a propyl-to-isopropyl replacement in the SPD molecule did not majorly affect the anticonvulsant activity.

  19. Inhibition of fatty acid amide hydrolase by URB597 attenuates the anxiolytic-like effect of acetaminophen in the mouse elevated plus-maze test.

    PubMed

    Zaitone, Sawsan A; El-Wakeil, Ahmed F; Abou-El-Ela, Soad H

    2012-08-01

    Acetaminophen is the most widely used analgesic/antipyretic drug. It is metabolized into N-arachidonoylphenolamine (AM404), which inhibits the reuptake of anandamide. In view of the role of endocannabinoids in the effect of acetaminophen, we tested its anxiolytic-like effect by observing the behavior of mice using the elevated plus-maze test. The results indicated that acetaminophen [100 and 200 mg/kg, intraperitoneally (i.p.)] exerted an anxiolytic-like effect that was represented by higher percentage open-arm time, percentage open-arm entries, and total number of head dips compared with the vehicle control (P<0.05). Inhibition of fatty acid amide hydrolase, an enzyme involved in the cerebral metabolism of acetaminophen into AM404, using URB597 (0.07 mg/kg, i.p.), attenuated the anxiolytic-like effect of acetaminophen. Pretreatment with the cannabinoid type-1 receptor antagonist rimonabant (1 mg/kg, i.p.) antagonized the effect of acetaminophen. Remarkably, the selected doses of rimonabant or URB597 did not themselves induce any anxiolytic-like effect. Furthermore, the selected doses of acetaminophen (25, 50, 100, and 200 mg/kg, i.p.) did not significantly alter the locomotor activity of mice in the open-field test. In conclusion, these findings confirmed that acetaminophen shows an anxiolytic-like effect in mice that involves, at least in part, AM404-mediated accumulation of anandamide in the brain and consequent activation of cannabinoid type-1 receptors.

  20. Fear-induced suppression of nociceptive behaviour and activation of Akt signalling in the rat periaqueductal grey: role of fatty acid amide hydrolase.

    PubMed

    Butler, Ryan K; Ford, Gemma K; Hogan, Michelle; Roche, Michelle; Doyle, Karen M; Kelly, John P; Kendall, David A; Chapman, Victoria; Finn, David P

    2012-01-01

    The endocannabinoid system regulates nociception and aversion and mediates fear-conditioned analgesia (FCA). We investigated the effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which inhibits the catabolism of the endocannabinoid anandamide and related N-acylethanolamines, on expression of FCA and fear and pain related behaviour per se in rats. We also examined associated alterations in the expression of the signal transduction molecule phospho-Akt in the periaqueductal grey (PAG) by immunoblotting. FCA was modelled by assessing formalin-evoked nociceptive behaviour in an arena previously paired with footshock. URB597 (0.3 mg/kg, i.p.) enhanced FCA and increased fear-related behaviour in formalin-treated rats. Conditioned fear per se in non-formalin-treated rats was associated with increased expression of phospho-Akt in the PAG. URB597 reduced the expression of fear-related behaviour in the early part of the trial, an effect that was accompanied by attenuation of the fear-induced increase in phospho-Akt expression in the PAG. Intra-plantar injection of formalin also reduced the fear-induced increase in phospho-Akt expression. These data provide evidence for a role of FAAH in FCA, fear responding in the presence or absence of nociceptive tone, and fear-evoked increases in PAG phospho-Akt expression. In addition, the results suggest that fear-evoked activation of Akt signalling in the PAG is abolished in the presence of nociceptive tone.

  1. Recognition of the folded conformation of plant hormone (auxin, IAA) conjugates with glutamic and aspartic acids and their amides

    NASA Astrophysics Data System (ADS)

    Antolić, S.; Kveder, M.; Klaić, B.; Magnus, V.; Kojić-Prodić, B.

    2001-01-01

    The molecular structure of the endogenous plant hormone (auxin) conjugate, N-(indol-3-ylacetyl)- L-glutamic acid, is deduced by comparison with N2-(indol-3-ylacetyl)glutamine (IAA-Gln), N2-(indol-3-ylacetyl)asparagine (IAA-Asn) and N-(indol-3-ylacetyl)- L-aspartic acid using X-ray structure analysis, 1H-NMR spectroscopy (NOE measurements) and molecular modelling. The significance of the overall molecular shape, and of the resulting amphiphilic properties, of the compounds studied are discussed in terms of possible implications for trafficking between cell compartments. Both in the solid state and in solution, the molecules are in the hair-pin (folded) conformation in which the side chain is folded over the indole ring. While extended conformations can be detected by molecular dynamics simulations, they are so short-lived that any major influence on the biological properties of the compounds studied is unlikely.

  2. Catalysis of the Carbonylation of Alcohols to Carboxylic Acids Including Acetic Acid Synthesis from Methanol.

    ERIC Educational Resources Information Center

    Forster, Denis; DeKleva, Thomas W.

    1986-01-01

    Monsanto's highly successful synthesis of acetic acid from methanol and carbon monoxide illustrates use of new starting materials to replace pretroleum-derived ethylene. Outlines the fundamental aspects of the acetic acid process and suggests ways of extending the synthesis to higher carboxylic acids. (JN)

  3. Poly(ester amide)s from Soybean Oil for Modulated Release and Bone Regeneration.

    PubMed

    Natarajan, Janeni; Dasgupta, Queeny; Shetty, Shreya N; Sarkar, Kishor; Madras, Giridhar; Chatterjee, Kaushik

    2016-09-28

    Designing biomaterials for bone tissue regeneration that are also capable of eluting drugs is challenging. Poly(ester amide)s are known for their commendable mechanical properties, degradation, and cellular response. In this regard, development of new poly(ester amide)s becomes imperative to improve the quality of lives of people affected by bone disorders. In this framework, a family of novel soybean oil based biodegradable poly(ester amide)s was synthesized based on facile catalyst-free melt-condensation reaction. The structure of the polymers was confirmed by FTIR and (1)H -NMR, which indicated the formation of the ester and amide bonds along the polymer backbone. Thermal analysis revealed the amorphous nature of the polymers. Contact angle and swelling studies proved that the hydrophobic nature increased with increase in chain length of the diacids and decreased with increase in molar ratio of sebacic acid. Mechanical studies proved that Young's modulus decreased with decrease in chain lengths of the diacids and increase in molar ratio of sebacic acid. The in vitro hydrolytic degradation and dye release demonstrated that the degradation and release decreased with increase in chain lengths of the diacids and increased with increase in molar ratio of sebacic acid. The degradation followed first order kinetics and dye release followed Higuchi kinetics. In vitro cell studies showed no toxic effects of the polymers. Osteogenesis studies revealed that the polymers can be remarkably efficient because more than twice the amount of minerals were deposited on the polymer surfaces than on the tissue culture polystyrene surfaces. Thus, a family of novel poly(ester amide)s has been synthesized, characterized for controlled release and tissue engineering applications wherein the physical, degradation, and release kinetics can be tuned by varying the monomers and their molar ratios. PMID:27599306

  4. Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-nitrogen cleavage: general strategy for amide N-C bond activation.

    PubMed

    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. Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-nitrogen cleavage: general strategy for amide N-C bond activation.

    PubMed

    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 (). PMID:26864384

  6. A 2:1 co-crystal of 2-methyl­benzoic acid and N,N′-bis­(pyridin-4-ylmeth­yl)ethanedi­amide: crystal structure and Hirshfeld surface analysis

    PubMed Central

    Syed, Sabrina; Jotani, Mukesh M.; Halim, Siti Nadiah Abdul; Tiekink, Edward R. T.

    2016-01-01

    The asymmetric unit of the title 2:1 co-crystal, 2C8H8O2·C14H14N4O2, comprises an acid mol­ecule in a general position and half a di­amide mol­ecule, the latter being located about a centre of inversion. In the acid, the carb­oxy­lic acid group is twisted out of the plane of the benzene ring to which it is attached [dihedral angle = 28.51 (8)°] and the carbonyl O atom and methyl group lie approximately to the same side of the mol­ecule [hy­droxy-O—C—C—C(H) torsion angle = −27.92 (17)°]. In the di­amide, the central C4N2O2 core is almost planar (r.m.s. deviation = 0.031 Å), and the pyridyl rings are perpendicular, lying to either side of the central plane [central residue/pyridyl dihedral angle = 88.60 (5)°]. In the mol­ecular packing, three-mol­ecule aggregates are formed via hy­droxy-O—H⋯N(pyrid­yl) hydrogen bonds. These are connected into a supra­molecular layer parallel to (12) via amide-N—H⋯O(carbon­yl) hydrogen bonds, as well as methyl­ene-C—H⋯O(amide) inter­actions. Significant π–π inter­actions occur between benzene/benzene, pyrid­yl/benzene and pyrid­yl/pyridyl rings within and between layers to consolidate the three-dimensional packing. PMID:27006815

  7. A 2:1 co-crystal of 2-methyl-benzoic acid and N,N'-bis-(pyridin-4-ylmeth-yl)ethanedi-amide: crystal structure and Hirshfeld surface analysis.

    PubMed

    Syed, Sabrina; Jotani, Mukesh M; Halim, Siti Nadiah Abdul; Tiekink, Edward R T

    2016-03-01

    The asymmetric unit of the title 2:1 co-crystal, 2C8H8O2·C14H14N4O2, comprises an acid mol-ecule in a general position and half a di-amide mol-ecule, the latter being located about a centre of inversion. In the acid, the carb-oxy-lic acid group is twisted out of the plane of the benzene ring to which it is attached [dihedral angle = 28.51 (8)°] and the carbonyl O atom and methyl group lie approximately to the same side of the mol-ecule [hy-droxy-O-C-C-C(H) torsion angle = -27.92 (17)°]. In the di-amide, the central C4N2O2 core is almost planar (r.m.s. deviation = 0.031 Å), and the pyridyl rings are perpendicular, lying to either side of the central plane [central residue/pyridyl dihedral angle = 88.60 (5)°]. In the mol-ecular packing, three-mol-ecule aggregates are formed via hy-droxy-O-H⋯N(pyrid-yl) hydrogen bonds. These are connected into a supra-molecular layer parallel to (12[Formula: see text]) via amide-N-H⋯O(carbon-yl) hydrogen bonds, as well as methyl-ene-C-H⋯O(amide) inter-actions. Significant π-π inter-actions occur between benzene/benzene, pyrid-yl/benzene and pyrid-yl/pyridyl rings within and between layers to consolidate the three-dimensional packing. PMID:27006815

  8. Fuel additives from SO/sub 2/ treated mixtures of amides and esters derived from vegetable oil, tall oil acid, or aralkyl acid

    SciTech Connect

    Efner, H. F.; Schiff, S.

    1985-03-12

    Vegetable oils, particularly soybean oil, tall oil acid, or aralkyl acids, particularly phenylstearic acid, are reacted with multiamines, particularly tetraethylenepentamine, to form a product mixture for subsequent reaction with SO/sub 2/ to produce a product mix that has good detergent properties in fuels.

  9. Antidepressant-like activity and cardioprotective effects of fatty acid amide hydrolase inhibitor URB694 in socially stressed Wistar Kyoto rats.

    PubMed

    Carnevali, Luca; Vacondio, Federica; Rossi, Stefano; Callegari, Sergio; Macchi, Emilio; Spadoni, Gilberto; Bedini, Annalida; Rivara, Silvia; Mor, Marco; Sgoifo, Andrea

    2015-11-01

    In humans, depression is often triggered by prolonged exposure to psychosocial stressors and is often associated with cardiovascular comorbidity. Mounting evidence suggests a role for endocannabinoid signaling in the regulation of both emotional behavior and cardiovascular function. Here, we examined cardiac activity in a rodent model of social stress-induced depression and investigated whether pharmacological inhibition of the enzyme fatty acid amide hydrolase (FAAH), which terminates signaling of the endocannabinoid anandamide, exerts antidepressant-like and cardioprotective effects. Male Wistar Kyoto rats were exposed to five weeks of repeated social stress or control procedure. Starting from the third week, they received daily administration of the selective FAAH inhibitor URB694 (0.1 mg/kg, i.p.) or vehicle. Cardiac electrical activity was recorded by radiotelemetry. Repeated social stress triggered biological and behavioral changes that mirror symptoms of human depression, such as (i) reductions in body weight gain and sucrose solution preference, (ii) hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and (iii) increased immobility in the forced swim test. Moreover, stressed rats showed (i) alterations in heart rate daily rhythm and cardiac autonomic neural regulation, (ii) a larger incidence of spontaneous arrhythmias, and (iii) signs of cardiac hypertrophy. Daily treatment with URB694 (i) increased central and peripheral anandamide levels, (ii) corrected stress-induced alterations of biological and behavioral parameters, and (iii) protected the heart against the adverse effects of social stress. Repeated social stress in Wistar Kyoto rats reproduces aspects of human depression/cardiovascular comorbidity. Pharmacological enhancement of anandamide signaling might be a promising strategy for the treatment of these comorbid conditions.

  10. Full Fatty Acid Amide Hydrolase Inhibition Combined with Partial Monoacylglycerol Lipase Inhibition: Augmented and Sustained Antinociceptive Effects with Reduced Cannabimimetic Side Effects in Mice

    PubMed Central

    Ghosh, Sudeshna; Kinsey, Steven G.; Liu, Qing-song; Hruba, Lenka; McMahon, Lance R.; Grim, Travis W.; Merritt, Christina R.; Wise, Laura E.; Abdullah, Rehab A.; Selley, Dana E.; Sim-Selley, Laura J.; Cravatt, Benjamin F.

    2015-01-01

    Inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), the primary hydrolytic enzymes for the respective endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonylglycerol (2-AG), produces antinociception but with minimal cannabimimetic side effects. Although selective inhibitors of either enzyme often show partial efficacy in various nociceptive models, their combined blockade elicits augmented antinociceptive effects, but side effects emerge. Moreover, complete and prolonged MAGL blockade leads to cannabinoid receptor type 1 (CB1) receptor functional tolerance, which represents another challenge in this potential therapeutic strategy. Therefore, the present study tested whether full FAAH inhibition combined with partial MAGL inhibition would produce sustained antinociceptive effects with minimal cannabimimetic side effects. Accordingly, we tested a high dose of the FAAH inhibitor PF-3845 (N-​3-​pyridinyl-​4-​[[3-​[[5-​(trifluoromethyl)-​2-​pyridinyl]oxy]phenyl]methyl]-​1-​piperidinecarboxamide; 10 mg/kg) given in combination with a low dose of the MAGL inhibitor JZL184 [4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate] (4 mg/kg) in mouse models of inflammatory and neuropathic pain. This combination of inhibitors elicited profound increases in brain AEA levels (>10-fold) but only 2- to 3-fold increases in brain 2-AG levels. This combination produced significantly greater antinociceptive effects than single enzyme inhibition and did not elicit common cannabimimetic effects (e.g., catalepsy, hypomotility, hypothermia, and substitution for Δ9-tetrahydrocannabinol in the drug-discrimination assay), although these side effects emerged with high-dose JZL184 (i.e., 100 mg/kg). Finally, repeated administration of this combination did not lead to tolerance to its antiallodynic actions in the carrageenan assay or CB1 receptor functional tolerance. Thus, full FAAH inhibition combined

  11. A multi-target approach for pain treatment: dual inhibition of fatty acid amide hydrolase and TRPV1 in a rat model of osteoarthritis.

    PubMed

    Malek, Natalia; Mrugala, Monika; Makuch, Wioletta; Kolosowska, Natalia; Przewlocka, Barbara; Binkowski, Marcin; Czaja, Martyna; Morera, Enrico; Di Marzo, Vincenzo; Starowicz, Katarzyna

    2015-05-01

    The pharmacological inhibition of anandamide (AEA) hydrolysis by fatty acid amide hydrolase (FAAH) attenuates pain in animal models of osteoarthritis (OA) but has failed in clinical trials. This may have occurred because AEA also activates transient receptor potential vanilloid type 1 (TRPV1), which contributes to pain development. Therefore, we investigated the effectiveness of the dual FAAH-TRPV1 blocker OMDM-198 in an MIA-model of osteoarthritic pain. We first investigated the MIA-induced model of OA by (1) characterizing the pain phenotype and degenerative changes within the joint using X-ray microtomography and (2) evaluating nerve injury and inflammation marker (ATF-3 and IL-6) expression in the lumbar dorsal root ganglia of osteoarthritic rats and differences in gene and protein expression of the cannabinoid CB1 receptors FAAH and TRPV1. Furthermore, we compared OMDM-198 with compounds acting exclusively on FAAH or TRPV1. Osteoarthritis was accompanied by the fragmentation of bone microstructure and destroyed cartilage. An increase of the mRNA levels of ATF3 and IL-6 and an upregulation of AEA receptors and FAAH in the dorsal root ganglia were observed. OMDM-198 showed antihyperalgesic effects in the OA model, which were comparable with those of a selective TRPV1 antagonist, SB-366,791, and a selective FAAH inhibitor, URB-597. The effect of OMDM-198 was attenuated by the CB1 receptor antagonist, AM-251, and by the nonpungent TRPV1 agonist, olvanil, suggesting its action as an "indirect" CB1 agonist and TRPV1 antagonist. These results suggest an innovative strategy for the treatment of OA, which may yield more satisfactory results than those obtained so far with selective FAAH inhibitors in human OA.

  12. Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context

    PubMed Central

    Rivera, Patricia; Bindila, Laura; Pastor, Antoni; Pérez-Martín, Margarita; Pavón, Francisco J.; Serrano, Antonia; de la Torre, Rafael; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3+ or BrdU+ cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3+), astroglia (GFAP+), and microglia (Iba1+ cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3+ and BrdU+ subgranular cells as well as GFAP+, Iba1+ and cleaved caspase-3+ cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3+, GFAP+ and 3-weeks-old BrdU+ cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context. PMID:25870539

  13. Influence of the degree of unsaturation of the acyl side chain upon the interaction of analogues of 1-arachidonoylglycerol with monoacylglycerol lipase and fatty acid amide hydrolase

    SciTech Connect

    Vandevoorde, Severine; Saha, Bijali; Mahadevan, Anu; Razdan, Raj K.; Pertwee, Roger G.; Martin, Billy R.; Fowler, Christopher J. . E-mail: cf@pharm.umu.se

    2005-11-11

    Little is known as to the structural requirements of the acyl side chain for interaction of acylglycerols with monoacylglycerol lipase (MAGL), the enzyme chiefly responsible for the metabolism of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain. In the present study, a series of twelve analogues of 1-AG (the more stable regioisomer of 2-AG) were investigated with respect to their ability to inhibit the metabolism of 2-oleoylglycerol by cytosolic and membrane-bound MAGL. In addition, the ability of the compounds to inhibit the hydrolysis of anandamide by fatty acid amide hydrolase (FAAH) was investigated. For cytosolic MAGL, compounds with 20 carbon atoms in the acyl chain and 2-5 unsaturated bonds inhibited the hydrolysis of 2-oleoylglycerol with similar potencies (IC{sub 50} values in the range 5.1-8.2 {mu}M), whereas the two compounds with a single unsaturated bond were less potent (IC{sub 50} values 19 and 21 {mu}M). The fully saturated analogue 1-monoarachidin did not inhibit the enzyme, whereas the lower side chain analogues 1-monopalmitin and 1-monomyristin inhibited the enzyme with IC{sub 50} values of 12 and 32 {mu}M, respectively. The 22-carbon chain analogue of 1-AG was also potent (IC{sub 50} value 4.5 {mu}M). Introduction of an {alpha}-methyl group for the C20:4, C20:3, and C22:4 compounds did not affect potency in a consistent manner. For the FAAH and the membrane-bound MAGL, there was no obvious relationship between the degree of unsaturation of the acyl side chain and the ability to inhibit the enzymes. It is concluded that increasing the number of unsaturated bonds on the acyl side chain of 1-AG from 1 to 5 has little effect on the affinity of acylglycerols for cytosolic MAGL.

  14. Involvement of endocannabinoids in alcohol “binge” drinking: studies of mice with human fatty acid amide hydrolase genetic variation and after CB1 receptor antagonists

    PubMed Central

    Zhou, Yan; Huang, Ted; Lee, Francis; Kreek, Mary Jeanne

    2016-01-01

    Background The endocannabinoid system has been found to play an important role in modulating alcohol intake. Inhibition or genetic deletion of fatty acid amide hydrolase (FAAH, a key catabolic enzyme for endocannabinoids) leads to increased alcohol consumption and preference in rodent models. A common human single-nucleotide polymorphism (SNP; C385A, rs324420) in the FAAH gene is associated with decreased enzymatic activity of FAAH, resulting in increased anandamide levels in both humans and FAAH C385A knock-in mice. Methods As this FAAH SNP has been reported to be associated with altered alcohol abuse, the present study used these genetic knock-in mice containing the human SNP C385A to determine the impact of variant FAAH gene on alcohol “binge” drinking in the drinking-in-the-dark (DID) model. Results We found that the FAAHA/A mice had greater alcohol intake and preference than the wild-type FAAHC/C mice, suggesting that increased endocannabinoid signaling in FAAHA/A mice led to increased alcohol “binge” consumption. The specificity on alcohol vulnerability was suggested by the lack of any FAAH genotype difference on sucrose or saccharin intake. Using the “binge” DID model, we confirmed that selective CB1 receptor antagonist AM251 reduced alcohol intake in the wild-type mice. Conclusions These data suggest that there is direct and selective involvement of the human FAAH C385A SNP and CB1 receptors in alcohol “binge” drinking. PMID:26857901

  15. Full Fatty Acid Amide Hydrolase Inhibition Combined with Partial Monoacylglycerol Lipase Inhibition: Augmented and Sustained Antinociceptive Effects with Reduced Cannabimimetic Side Effects in Mice.

    PubMed

    Ghosh, Sudeshna; Kinsey, Steven G; Liu, Qing-Song; Hruba, Lenka; McMahon, Lance R; Grim, Travis W; Merritt, Christina R; Wise, Laura E; Abdullah, Rehab A; Selley, Dana E; Sim-Selley, Laura J; Cravatt, Benjamin F; Lichtman, Aron H

    2015-08-01

    Inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), the primary hydrolytic enzymes for the respective endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonylglycerol (2-AG), produces antinociception but with minimal cannabimimetic side effects. Although selective inhibitors of either enzyme often show partial efficacy in various nociceptive models, their combined blockade elicits augmented antinociceptive effects, but side effects emerge. Moreover, complete and prolonged MAGL blockade leads to cannabinoid receptor type 1 (CB1) receptor functional tolerance, which represents another challenge in this potential therapeutic strategy. Therefore, the present study tested whether full FAAH inhibition combined with partial MAGL inhibition would produce sustained antinociceptive effects with minimal cannabimimetic side effects. Accordingly, we tested a high dose of the FAAH inhibitor PF-3845 (N-​3-​pyridinyl-​4-​[[3-​[[5-​(trifluoromethyl)-​2-​pyridinyl]oxy]phenyl]methyl]-​1-​piperidinecarboxamide; 10 mg/kg) given in combination with a low dose of the MAGL inhibitor JZL184 [4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate] (4 mg/kg) in mouse models of inflammatory and neuropathic pain. This combination of inhibitors elicited profound increases in brain AEA levels (>10-fold) but only 2- to 3-fold increases in brain 2-AG levels. This combination produced significantly greater antinociceptive effects than single enzyme inhibition and did not elicit common cannabimimetic effects (e.g., catalepsy, hypomotility, hypothermia, and substitution for Δ(9)-tetrahydrocannabinol in the drug-discrimination assay), although these side effects emerged with high-dose JZL184 (i.e., 100 mg/kg). Finally, repeated administration of this combination did not lead to tolerance to its antiallodynic actions in the carrageenan assay or CB1 receptor functional tolerance. Thus, full FAAH inhibition

  16. Antidepressant-like activity and cardioprotective effects of fatty acid amide hydrolase inhibitor URB694 in socially stressed Wistar Kyoto rats.

    PubMed

    Carnevali, Luca; Vacondio, Federica; Rossi, Stefano; Callegari, Sergio; Macchi, Emilio; Spadoni, Gilberto; Bedini, Annalida; Rivara, Silvia; Mor, Marco; Sgoifo, Andrea

    2015-11-01

    In humans, depression is often triggered by prolonged exposure to psychosocial stressors and is often associated with cardiovascular comorbidity. Mounting evidence suggests a role for endocannabinoid signaling in the regulation of both emotional behavior and cardiovascular function. Here, we examined cardiac activity in a rodent model of social stress-induced depression and investigated whether pharmacological inhibition of the enzyme fatty acid amide hydrolase (FAAH), which terminates signaling of the endocannabinoid anandamide, exerts antidepressant-like and cardioprotective effects. Male Wistar Kyoto rats were exposed to five weeks of repeated social stress or control procedure. Starting from the third week, they received daily administration of the selective FAAH inhibitor URB694 (0.1 mg/kg, i.p.) or vehicle. Cardiac electrical activity was recorded by radiotelemetry. Repeated social stress triggered biological and behavioral changes that mirror symptoms of human depression, such as (i) reductions in body weight gain and sucrose solution preference, (ii) hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and (iii) increased immobility in the forced swim test. Moreover, stressed rats showed (i) alterations in heart rate daily rhythm and cardiac autonomic neural regulation, (ii) a larger incidence of spontaneous arrhythmias, and (iii) signs of cardiac hypertrophy. Daily treatment with URB694 (i) increased central and peripheral anandamide levels, (ii) corrected stress-induced alterations of biological and behavioral parameters, and (iii) protected the heart against the adverse effects of social stress. Repeated social stress in Wistar Kyoto rats reproduces aspects of human depression/cardiovascular comorbidity. Pharmacological enhancement of anandamide signaling might be a promising strategy for the treatment of these comorbid conditions. PMID:26391492

  17. Assessing the Risk That Phytophthora melonis Can Develop a Point Mutation (V1109L) in CesA3 Conferring Resistance to Carboxylic Acid Amide Fungicides

    PubMed Central

    Chen, Lei; Zhu, Shusheng; Lu, Xiaohong; Pang, Zhili; Cai, Meng; Liu, Xili

    2012-01-01

    The risk that the plant pathogen Phytophthora melonis develops resistance to carboxylic acid amide (CAA) fungicides was determined by measuring baseline sensitivities of field isolates, generating resistant mutants, and measuring the fitness of the resistant mutants. The baseline sensitivities of 80 isolates to flumorph, dimethomorph and iprovalicarb were described by unimodal curves, with mean EC50 values of 0.986 (±0.245), 0.284 (±0.060) and 0.327 (±0.068) µg/ml, respectively. Seven isolates with different genetic background (as indicated by RAPD markers) were selected to generate CAA-resistance. Fifty-five resistant mutants were obtained from three out of seven isolates by spontaneous selection and UV-mutagenesis with frequencies of 1×10−7 and 1×10−6, respectively. CAA-resistance was stable for all mutants. The resistance factors of these mutants ranged from 7 to 601. The compound fitness index (CFI  =  mycelial growth × zoospore production × pathogenicity) was often lower for the CAA-resistant isolates than for wild-type isolates, suggesting that the risk of P. melonis developing resistance to CAA fungicides is low to moderate. Among the CAA-resistant isolates, a negative correlation between EC50 values was found for iprovalicarb vs. flumorph and for iprovalicarb vs. dimethomorph. Comparison of the full-length cellulose synthase 3 (CesA3) between wild-type and CAA-resistant isolates revealed only one point mutation at codon position 1109: a valine residue (codon GTG in wild-type isolates) was converted to leucine (codon CTG in resistant mutants). This represents a novel point mutation with respect to mutations in CesA3 conferring resistance to CAA fungicides. Based on this mutation, an efficient allelic-specific PCR (AS-PCR) method was developed for rapid detection of CAA-resistance in P. melonis populations. PMID:22848705

  18. Benzoisothiazolone Organo/Copper-Cocatalyzed Redox Dehydrative Construction of Amides and Peptides from Carboxylic Acids using (EtO)3P as the Reductant and O2 in Air as the Terminal Oxidant.

    PubMed

    Liebeskind, Lanny S; Gangireddy, Pavankumar; Lindale, Matthew G

    2016-06-01

    Carboxylic acids and amine/amino acid reactants can be converted to amides and peptides at neutral pH within 5-36 h at 50 °C using catalytic quantities of a redox-active benzoisothiazolone and a copper complex. These catalytic "oxidation-reduction condensation" reactions are carried out open to dry air using O2 as the terminal oxidant and a slight excess of triethyl phosphite as the reductant. Triethyl phosphate is the easily removed byproduct. These simple-to-run catalytic reactions provide practical and economical procedures for the acylative construction of C-N bonds. PMID:27175892

  19. Polymerase chain reaction system using magnetic beads for analyzing a sample that includes nucleic acid

    DOEpatents

    Nasarabadi, Shanavaz

    2011-01-11

    A polymerase chain reaction system for analyzing a sample containing nucleic acid includes providing magnetic beads; providing a flow channel having a polymerase chain reaction chamber, a pre polymerase chain reaction magnet position adjacent the polymerase chain reaction chamber, and a post pre polymerase magnet position adjacent the polymerase chain reaction chamber. The nucleic acid is bound to the magnetic beads. The magnetic beads with the nucleic acid flow to the pre polymerase chain reaction magnet position in the flow channel. The magnetic beads and the nucleic acid are washed with ethanol. The nucleic acid in the polymerase chain reaction chamber is amplified. The magnetic beads and the nucleic acid are separated into a waste stream containing the magnetic beads and a post polymerase chain reaction mix containing the nucleic acid. The reaction mix containing the nucleic acid flows to an analysis unit in the channel for analysis.

  20. Incorporation of hydrogen atoms from deuterated water and stereospecifically deuterium-labeled nicotin amide nucleotides into fatty acids with the Escherichia coli fatty acid synthetase system.

    PubMed

    Saito, K; Kawaguchi, A; Okuda, S; Seyama, Y; Yamakawa, T

    1980-05-28

    The mechanism of hydrogen incorporation into fatty acids was investigated with intact Escherichia coli cells, a crude enzyme preparation and purified reductases of fatty acid synthetase system. The distributions of deuterium atoms incorporated into fatty acids from 2H2O and stereospecifically deuterium-labeled NADPH or NADH were determined by mass spectrometry. When E. coli was grown in 2H2O, almost every hydrogen atom of cellular fatty acids was incorporated from the medium. When fatty acids were synthesized from acetyl-CoA, malonyl-CoA and NADPH in the presence of a crude enzyme preparation of either E. coli or Bacillus subtilis, almost every hydrogen atom was also incorporated from the medium. In contrast to these results, purified beta-ketoacyl acyl carrier reductase directly transferred the HB hydrogen of NADPH to beta-ketoacyl acyl carrier protein, and purified enoyl acyl carrier protein reductase also transferred the HB hydrogen of NADPH and NADH directly to enoyl acyl carrier protein. In the crude enzyme preparation of E. coli, we found high activities which exchanged the HB hydrogen of NADPH with the deuterium of 2h2o. the conflicting results of the origin of hydrogen atoms of fatty acids mentioned above are explained by the presence of enzymes, which catalyzed the rapid exchange of NADPH with the deterium of 2H2O prior to the reaction of fatty acid synthetase. PMID:6990992

  1. How amide hydrogens exchange in native proteins

    PubMed Central

    Persson, Filip; Halle, Bertil

    2015-01-01

    Amide hydrogen exchange (HX) is widely used in protein biophysics even though our ignorance about the HX mechanism makes data interpretation imprecise. Notably, the open exchange-competent conformational state has not been identified. Based on analysis of an ultralong molecular dynamics trajectory of the protein BPTI, we propose that the open (O) states for amides that exchange by subglobal fluctuations are locally distorted conformations with two water molecules directly coordinated to the N–H group. The HX protection factors computed from the relative O-state populations agree well with experiment. The O states of different amides show little or no temporal correlation, even if adjacent residues unfold cooperatively. The mean residence time of the O state is ∼100 ps for all examined amides, so the large variation in measured HX rate must be attributed to the opening frequency. A few amides gain solvent access via tunnels or pores penetrated by water chains including native internal water molecules, but most amides access solvent by more local structural distortions. In either case, we argue that an overcoordinated N–H group is necessary for efficient proton transfer by Grotthuss-type structural diffusion. PMID:26195754

  2. Strong Bonds Made Weak: Towards the General Utility of Amides as Synthetic Modules.

    PubMed

    Ruider, Stefan A; Maulide, Nuno

    2015-11-16

    Breaking good: The amide bond is widely recognized as the strongest bond among the carboxylic acid derivatives. Therefore, the potential of amides to serve as synthetic building blocks has remained mostly untapped thus far. This Highlight describes a recent breakthrough that enables the catalytic conversion of amides into esters for the first time. PMID:26460213

  3. Enzymes utilizing glutamine as an amide donor.

    PubMed

    Zalkin, H; Smith, J L

    1998-01-01

    Amide nitrogen from glutamine is a major source of nitrogen atoms incorporated biosynthetically into other amino acids, purine and pyrimidine bases, amino-sugars, and coenzymes. A family comprised of at least sixteen amidotransferases are known to catalyze amide nitrogen transfer from glutamine to their acceptor substrates. Recent fine structural advances, largely as a result of X-ray crystallography, now provide structure-based mechanisms that help to explain fundamental aspects of the catalytic and regulatory interactions of several of these aminotransferases. This chapter provides an overview of this recent progress made on the characterization of amidotransferase structure and mechanism. PMID:9559052

  4. The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats

    PubMed Central

    2011-01-01

    Background Neuropathic pain is a chronic disease resulting from dysfunction within the "pain matrix". The basolateral amygdala (BLA) can modulate cortical functions and interactions between this structure and the medial prefrontal cortex (mPFC) are important for integrating emotionally salient information. In this study, we have investigated the involvement of the transient receptor potential vanilloid type 1 (TRPV1) and the catabolic enzyme fatty acid amide hydrolase (FAAH) in the morphofunctional changes occurring in the pre-limbic/infra-limbic (PL/IL) cortex in neuropathic rats. Results The effect of N-arachidonoyl-serotonin (AA-5-HT), a hybrid FAAH inhibitor and TPRV1 channel antagonist, was tested on nociceptive behaviour associated with neuropathic pain as well as on some phenotypic changes occurring on PL/IL cortex pyramidal neurons. Those neurons were identified as belonging to the BLA-mPFC pathway by electrical stimulation of the BLA followed by hind-paw pressoceptive stimulus application. Changes in their spontaneous and evoked activity were studied in sham or spared nerve injury (SNI) rats before or after repeated treatment with AA-5-HT. Consistently with the SNI-induced changes in PL/IL cortex neurons which underwent profound phenotypic reorganization, suggesting a profound imbalance between excitatory and inhibitory responses in the mPFC neurons, we found an increase in extracellular glutamate levels, as well as the up-regulation of FAAH and TRPV1 in the PL/IL cortex of SNI rats. Daily treatment with AA-5-HT restored cortical neuronal activity, normalizing the electrophysiological changes associated with the peripheral injury of the sciatic nerve. Finally, a single acute intra-PL/IL cortex microinjection of AA-5-HT transiently decreased allodynia more effectively than URB597 or I-RTX, a selective FAAH inhibitor or a TRPV1 blocker, respectively. Conclusion These data suggest a possible involvement of endovanilloids in the cortical plastic changes

  5. Ultrasound-assisted direct oxidative amidation of benzyl alcohols catalyzed by graphite oxide.

    PubMed

    Mirza-Aghayan, Maryam; Ganjbakhsh, Nahid; Molaee Tavana, Mahdieh; Boukherroub, Rabah

    2016-09-01

    Ultrasound irradiation was successfully applied for the direct oxidative amidation of benzyl alcohols with amines into the corresponding amides using graphite oxide (GO) as an oxidative and reusable solid acid catalyst in acetonitrile as solvent at 50°C under air atmosphere. The direct oxidative amidation of benzyl alcohols takes place under mild conditions yielding the corresponding amides in good to high yields (69-95%) and short reaction times under metal-free conditions.

  6. Ultrasound-assisted direct oxidative amidation of benzyl alcohols catalyzed by graphite oxide.

    PubMed

    Mirza-Aghayan, Maryam; Ganjbakhsh, Nahid; Molaee Tavana, Mahdieh; Boukherroub, Rabah

    2016-09-01

    Ultrasound irradiation was successfully applied for the direct oxidative amidation of benzyl alcohols with amines into the corresponding amides using graphite oxide (GO) as an oxidative and reusable solid acid catalyst in acetonitrile as solvent at 50°C under air atmosphere. The direct oxidative amidation of benzyl alcohols takes place under mild conditions yielding the corresponding amides in good to high yields (69-95%) and short reaction times under metal-free conditions. PMID:27150743

  7. Fluoride-Mediated Capture of a Noncovalent Bound State of a Reversible Covalent Enzyme Inhibitor: X-ray Crystallographic Analysis of an Exceptionally Potent [alpha]-Ketoheterocycle Inhibitor of Fatty Acid Amide Hydrolase

    SciTech Connect

    Mileni, Mauro; Garfunkle, Joie; Ezzili, Cyrine; Cravatt, Benjamin F.; Stevens, Raymond C.; Boger, Dale L.

    2011-11-02

    Two cocrystal X-ray structures of the exceptionally potent {alpha}-ketoheterocycle inhibitor 1 (K{sub i} = 290 pM) bound to a humanized variant of rat fatty acid amide hydrolase (FAAH) are disclosed, representing noncovalently and covalently bound states of the same inhibitor with the enzyme. Key to securing the structure of the noncovalently bound state of the inhibitor was the inclusion of fluoride ion in the crystallization conditions that is proposed to bind the oxyanion hole precluding inhibitor covalent adduct formation with stabilization of the tetrahedral hemiketal. This permitted the opportunity to detect important noncovalent interactions stabilizing the binding of the inhibitor within the FAAH active site independent of the covalent reaction. Remarkably, noncovalently bound 1 in the presence of fluoride appears to capture the active site in the same 'in action' state with the three catalytic residues Ser241-Ser217-Lys142 occupying essentially identical positions observed in the covalently bound structure of 1, suggesting that this technique of introducing fluoride may have important applications in structural studies beyond inhibiting substrate or inhibitor oxyanion hole binding. Key insights to emerge from the studies include the observations that noncovalently bound 1 binds in its ketone (not gem diol) form, that the terminal phenyl group in the acyl side chain of the inhibitor serves as the key anchoring interaction overriding the intricate polar interactions in the cytosolic port, and that the role of the central activating heterocycle is dominated by its intrinsic electron-withdrawing properties. These two structures are also briefly compared with five X-ray structures of {alpha}-ketoheterocycle-based inhibitors bound to FAAH recently disclosed.

  8. Cannabinoid receptor agonist WIN55,212-2 and fatty acid amide hydrolase inhibitor URB597 may protect against cognitive impairment in rats of chronic cerebral hypoperfusion via PI3K/AKT signaling.

    PubMed

    Su, Shao-Hua; Wang, Yue-Qing; Wu, Yi-Fang; Wang, Da-Peng; Lin, Qi; Hai, Jian

    2016-10-15

    The present study further investigated the protective effects of cannabinoid receptor agonist WIN55,212-2 (WIN) and fatty acid amide hydrolase (FAAH) inhibitor URB597 (URB) on chronic cerebral hypoperfusion (CCH)-induced cognitive impairment in rats. Spatial learning and memory were assessed with the Morris water maze and by measuring Long-term potentiation. The expression of microtubule-associated protein-2 (MAP)-2, growth-associated protein-43 (GAP)-43, synaptophysin, cannabinoid receptor 1 (CB1), brain-derived neurotrophic factor (BDNF), FAAH, N-acylphosphatidylethanolamine phospholipase D(NAPE-PLD) and monoacyl glycerol lipase (MGL) as well as phosphoinositide 3-kinase (PI3K)/AKT signaling pathway molecules and downstream targets including AKT, phosphorylated (p-)AKT, cyclic AMP response element- binding protein (CREB), p-CREB, Bcl-2-associated death protein (BAD), p-BAD, glycogen synthase kinase (GSK)-3β, p-GSK-3β, forkhead box protein (FOXO) 3A and p-FOXO3A was determined by western blotting. WIN and URB treatment improved learning and memory performance, effects that were abolished by co-administration of the PI3K/AKT inhibitor LY294002. Moreover, WIN and URB reversed the decreases in MAP-2 and synaptophysin expression resulting from CCH, and stimulated BDNF and CB1 expression as well as CREB, FOXO3A, GSK-3β, and BAD phosphorylation, confirming that WIN and URB mediate neuroprotection by preventing neuronal apoptosis and improving cognition via PI3K/AKT signaling. These findings suggest that WIN and URB are promising agents for therapeutic management of CCH. PMID:27424778

  9. Effect of omega-3 fatty acids on the modification of erythrocyte membrane fatty acid content including oleic acid in peritoneal dialysis patients.

    PubMed

    An, W S; Lee, S M; Son, Y K; Kim, S E; Kim, K H; Han, J Y; Bae, H R; Park, Y

    2012-01-01

    Erythrocyte membrane fatty acids (FA), such as oleic acid, are related to acute coronary syndrome. There is no report about the effect of omega-3 FA on oleic acid in peritoneal dialysis (PD) patients. We hypothesized that omega-3 FA can modify erythrocyte membrane FA, including oleic acid, in PD patients. In a double-blind, randomized, placebo-controlled study, 18 patients who were treated with PD for at least 6 months were randomized to treatment for 12 weeks with omega-3 FA or placebo. Erythrocyte membrane FA content was measured by gas chromatography at baseline and after 12 weeks. The erythrocyte membrane content of eicosapentaenoic acid and docosahexaenoic acid was significantly increased and saturated FA and oleic acid were significantly decreased in the omega-3 FA supplementation group after 12 weeks compared to baseline. In conclusion, erythrocyte membrane FA content, including oleic acid, was significantly modified by omega-3 FA supplementation for 12 weeks in PD patients.

  10. Synthesis of a novel biologically active amide ester of 7,10-dihydroxy-8(E)-octadecanoic acid (DOD) using lipase

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydroxy fatty acids (HFA) are known to have industrial potential because of their special properties such as high viscosity and reactivity. Among the hydroxy fatty acids, 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) was successfully produced from oleic acid and lipid containing oleic acid by a bacter...

  11. Side chain dependence of intensity and wavenumber position of amide I' in IR and visible Raman spectra of XA and AX dipeptides.

    PubMed

    Measey, Thomas; Hagarman, Andrew; Eker, Fatma; Griebenow, Kai; Schweitzer-Stenner, Reinhard

    2005-04-28

    A series of AX and XA dipeptides in D2O have been investigated by FTIR, isotropic, and anisotropic Raman spectroscopy at acidic, neutral, and alkaline pD, to probe the influence of amino acid side chains on the amide I' band. We obtained a set of spectral parameters for each peptide, including intensities, wavenumbers, half-widths, and dipole moments, and found that these amide I' parameters are indeed dependent on the side chain. Side chains with similar characteristic properties were found to have similar effects on the amide I'. For example, dipeptides with aliphatic side chains were found to exhibit a downshift of the amide I' wavenumber, while those containing polar side chains experienced an increase in wavenumber. The N-terminal charge causes a substantial upshift of amide I', whereas the C-terminal charge causes a moderate decrease of the transition dipole moment. Density functional theory (DFT) calculations on the investigated dipeptides in vacuo yielded different correlations between theoretically and experimentally obtained wavenumbers for aliphatic/aromatic and polar/charged side chains, respectively. This might be indicative of a role of the hydration shell in transferring side chain-backbone interactions. For Raman bands, we found a correlation between amide I' depolarization ratio and wavenumber which reflects that some side chains (valine, histidine) have a significant influence on the Raman tensor. Altogether, the obtained data are of utmost importance for utilizing amide I as a tool for secondary structure analysis of polypeptides and proteins and providing an experimental basis for theoretical modeling of this important backbone mode. This is demonstrated by a rather accurate modeling for the amide I' band profiles of the IR, isotropic Raman, and anisotropic Raman spectra of the beta-amyloid fragment Abeta(1-82).

  12. A new cytotoxic amide from the stem wood of Hibiscus tiliaceus.

    PubMed

    Chen, Jih-Jung; Huang, Shi-Yu; Duh, Chang-Yih; Chen, Ih-Sheng; Wang, Tai-Chi; Fang, Hui-Yu

    2006-08-01

    A new coumarin, hibiscusin, and a new amide, hibiscusamide, together with eleven known compounds including vanillic acid, P-hydroxybenzoic acid, syringic acid, P-hydroxybenzaldehyde, scopoletin, N- trans-feruloyltyramine, N-cis-feruloyltyramine, a mixture of beta-sitosterol and stigmasterol, a mixture of beta-sitostenone and stigmasta-4,22-dien-3-one were isolated from the stem wood of Hibiscus tiliaceus. The structures of these new compounds were determined through spectral analyses. Among the isolates, three compounds exhibited cytotoxicity (IC (50) values < 4 microg/mL) against P-388 and/or HT-29 cell lines in vitro.

  13. Fatty Acid Composition of Egg Yolk from Chickens Fed a Diet including Marigold (Tagetes erecta L.)

    PubMed Central

    Altuntaş, A.; Aydin, R.

    2014-01-01

    The objective of this study was to determine the effects of diet supplemented with marigold on egg yolk fatty acid composition and egg quality parameters. Sixty hens were assigned into three groups and fed diets supplemented with 0 (control), 10 g kg−1, or 20 g kg−1 marigold for 42 days. Eggs collected at the 6th week of the study were analyzed for fatty acid analysis. Laying performance, egg quality parameters, and feed intake were also evaluated. Yolk color scores in the group fed the 20 g kg−1 marigold-supplemented diet were found greater than control (10.77 versus 9.77). Inclusion of 20 g kg−1 marigold in diet influenced egg weights adversely compared to the control. Diet supplemented with 10 g kg−1 or 20 g kg−1 marigold increased the levels of C16:0 and C18:0 and decreased levels of C16:1 (n-7) and C18:1 (n-9) in the egg yolk. Also, diet including marigold increased total saturated fatty acids (SFA) and decreased monounsaturated fatty acids (MUFA) in the egg yolk. PMID:25587451

  14. Fatty Acid Composition of Egg Yolk from Chickens Fed a Diet including Marigold (Tagetes erecta L.).

    PubMed

    Altuntaş, A; Aydin, R

    2014-01-01

    The objective of this study was to determine the effects of diet supplemented with marigold on egg yolk fatty acid composition and egg quality parameters. Sixty hens were assigned into three groups and fed diets supplemented with 0 (control), 10 g kg(-1), or 20 g kg(-1) marigold for 42 days. Eggs collected at the 6th week of the study were analyzed for fatty acid analysis. Laying performance, egg quality parameters, and feed intake were also evaluated. Yolk color scores in the group fed the 20 g kg(-1) marigold-supplemented diet were found greater than control (10.77 versus 9.77). Inclusion of 20 g kg(-1) marigold in diet influenced egg weights adversely compared to the control. Diet supplemented with 10 g kg(-1) or 20 g kg(-1) marigold increased the levels of C16:0 and C18:0 and decreased levels of C16:1 (n-7) and C18:1 (n-9) in the egg yolk. Also, diet including marigold increased total saturated fatty acids (SFA) and decreased monounsaturated fatty acids (MUFA) in the egg yolk. PMID:25587451

  15. An algorithm for computing nucleic acid base-pairing probabilities including pseudoknots.

    PubMed

    Dirks, Robert M; Pierce, Niles A

    2004-07-30

    Given a nucleic acid sequence, a recent algorithm allows the calculation of the partition function over secondary structure space including a class of physically relevant pseudoknots. Here, we present a method for computing base-pairing probabilities starting from the output of this partition function algorithm. The approach relies on the calculation of recursion probabilities that are computed by backtracking through the partition function algorithm, applying a particular transformation at each step. This transformation is applicable to any partition function algorithm that follows the same basic dynamic programming paradigm. Base-pairing probabilities are useful for analyzing the equilibrium ensemble properties of natural and engineered nucleic acids, as demonstrated for a human telomerase RNA and a synthetic DNA nanostructure. PMID:15139042

  16. A novel and orally active poly(ADP-ribose) polymerase inhibitor, KR-33889 [2-[methoxycarbonyl(4-methoxyphenyl) methylsulfanyl]-1H-benzimidazole-4-carboxylic acid amide], attenuates injury in in vitro model of cell death and in vivo model of cardiac ischemia.

    PubMed

    Oh, Kwang-Seok; Lee, Sunkyung; Yi, Kyu Yang; Seo, Ho Won; Koo, Hyun-Na; Lee, Byung Ho

    2009-01-01

    Blocking of poly(ADP-ribose) polymerase (PARP)-1 has been expected to protect the heart from ischemia-reperfusion injury. We have recently identified a novel and orally active PARP-1 inhibitor, KR-33889 [2-[methoxycarbonyl(4-methoxyphenyl)-methylsulfanyl]-1H-benzimidazole-4-carboxylic acid amide], and its major metabolite, KR-34285 [2-[carboxy(4-methoxyphenyl)methylsulfanyl]-1H-benzimidazole-4-carboxylic acid amide]. KR-33889 potently inhibited PARP-1 activity with an IC(50) value of 0.52 +/- 0.10 microM. In H9c2 myocardial cells, KR-33889 (0.03-30 microM) showed a resistance to hydrogen peroxide (2 mM)-mediated oxidative insult and significantly attenuated activation of intracellular PARP-1. In anesthetized rats subjected to 30 min of coronary occlusion and 3 h of reperfusion, KR-33889 (0.3-3 mg/kg i.v.) dose-dependently reduced myocardial infarct size. KR-34285, a major metabolite of KR-33889, exerted similar patterns to the parent compound with equi- or weaker potency in the same studies described above. In separate experiments for the therapeutic time window study, KR-33889 (3 mg/kg i.v.) given at preischemia, at reperfusion or in both, in rat models also significantly reduced the myocardial infarction compared with their respective vehicle-treated group. Furthermore, the oral administration of KR-33889 (1-10 mg/kg p.o.) at 1 h before occlusion significantly reduced myocardial injury. The ability of KR-33889 to inhibit PARP in the rat model of ischemic heart was confirmed by immunohistochemical detection of poly(ADP-ribose) activation. These results indicate that the novel PARP inhibitor KR-33889 exerts its cardioprotective effect in in vitro and in vivo studies of myocardial ischemia via potent PARP inhibition and also suggest that KR-33889 could be an attractive therapeutic candidate with oral activity for several cardiovascular disorders, including myocardial infarction.

  17. CycloPs: generating virtual libraries of cyclized and constrained peptides including nonnatural amino acids.

    PubMed

    Duffy, Fergal J; Verniere, Mélanie; Devocelle, Marc; Bernard, Elise; Shields, Denis C; Chubb, Anthony J

    2011-04-25

    We introduce CycloPs, software for the generation of virtual libraries of constrained peptides including natural and nonnatural commercially available amino acids. The software is written in the cross-platform Python programming language, and features include generating virtual libraries in one-dimensional SMILES and three-dimensional SDF formats, suitable for virtual screening. The stand-alone software is capable of filtering the virtual libraries using empirical measurements, including peptide synthesizability by standard peptide synthesis techniques, stability, and the druglike properties of the peptide. The software and accompanying Web interface is designed to enable the rapid generation of large, structurally diverse, synthesizable virtual libraries of constrained peptides quickly and conveniently, for use in virtual screening experiments. The stand-alone software, and the Web interface for evaluating these empirical properties of a single peptide, are available at http://bioware.ucd.ie .

  18. Amino acid composition, including key derivatives of eccrine sweat: potential biomarkers of certain atopic skin conditions.

    PubMed

    Mark, Harker; Harding, Clive R

    2013-04-01

    The free amino acid (AA) composition of eccrine sweat is different from other biological fluids, for reasons which are not properly understood. We undertook the detailed analysis of the AA composition of freshly isolated pure human eccrine sweat, including some of the key derivatives of AA metabolism, to better understand the key biological mechanisms governing its composition. Eccrine sweat was collected from the axillae of 12 healthy subjects immediately upon formation. Free AA analysis was performed using an automatic AA analyser after ninhydrin derivatization. Pyrrolidine-5-carboxylic acid (PCA) and urocanic acid (UCA) levels were determined using GC/MS. The free AA composition of sweat was dominated by the presence of serine accounting for just over one-fifth of the total free AA composition. Glycine was the next most abundant followed by PCA, alanine, citrulline and threonine, respectively. The data obtained indicate that the AA content of sweat bears a remarkable similarity to the AA composition of the epidermal protein profilaggrin. This protein is the key source of free AAs and their derivatives that form a major part of the natural moisturizing factor (NMF) within the stratum corneum (SC) and plays a major role in maintaining the barrier integrity of human skin. As perturbations in the production of NMF can lead to abnormal barrier function and can arise as a consequence of filaggrin genotype, we propose the quantification of AAs in sweat may serve as a non-invasive diagnostic biomarker for certain atopic skin conditions, that is, atopic dermatitis (AD).

  19. Murine elongation factor 1 alpha (EF-1 alpha) is posttranslationally modified by novel amide-linked ethanolamine-phosphoglycerol moieties. Addition of ethanolamine-phosphoglycerol to specific glutamic acid residues on EF-1 alpha

    SciTech Connect

    Whiteheart, S.W.; Shenbagamurthi, P.; Chen, L.; Cotter, R.J.; Hart, G.W. )

    1989-08-25

    Elongation Factor 1 alpha (EF-1 alpha), an important eukaryotic translation factor, transports charged aminoacyl-tRNA from the cytosol to the ribosomes during poly-peptide synthesis. Metabolic radiolabeling with ({sup 3}H) ethanolamine shows that, in all cells examined, EF-1 alpha is the major radiolabeled protein. Radiolabeled EF-1 alpha has an apparent Mr = 53,000 and a basic isoelectric point. It is cytosolic and does not contain N-linked oligosaccharides. Trypsin digestion of murine EF-1 alpha generated two major ({sup 3}H)ethanolamine-labeled peptides. Three peptides were sequenced and were identical to two distinct regions of the human EF-1 alpha protein. Blank sequencing cycles coinciding with glutamic acid in the human cDNA-derived sequence were also found to release ({sup 3}H)ethanolamine, and compositional analysis of these peptides confirmed the presence of glutamic acid. Dansylation analysis demonstrates that the amine group of the ethanolamine is blocked. These results indicate that EF-1 alpha is posttranslationally modified by the covalent attachment of ethanolamine via an amide bond to at least two specific glutamic acid residues (Glu-301 and Glu-374). The hydroxyl group of the attached ethanolamine was shown by mass spectrometry and compositional analysis, to be further modified by the addition of a phosphoglycerol unit. This novel posttranslational modification may represent an important alteration of EF-1 alpha, comparable to the regulatory effects of posttranslational methylation of EF-1 alpha lysine residues.

  20. 1-Heteroaryl-3-phenoxypropan-2-ones as inhibitors of cytosolic phospholipase A₂α and fatty acid amide hydrolase: Effect of the replacement of the ether oxygen with sulfur and nitrogen moieties on enzyme inhibition and metabolic stability.

    PubMed

    Sundermann, Tom; Fabian, Jörg; Hanekamp, Walburga; Lehr, Matthias

    2015-05-15

    Cytosolic phospholipase A2α (cPLA2α) and fatty acid amide hydrolase (FAAH) are enzymes, which have emerged as attractive targets for the development of analgesic and anti-inflammatory drugs. We recently reported that certain 3-phenoxy-substituted 1-heteroarylpropan-2-ones are inhibitors of cPLA2α and/or FAAH. Starting from 1-[2-oxo-3-(4-phenoxyphenoxy)propyl]indole-5-carboxylic acid (3) and 1-(1H-benzotriazol-1-yl)-3-(4-phenoxyphenoxy)propan-2-one (4), the effect of the replacement of the oxygen in position 3 of the propan-2-one scaffold by sulfur and nitrogen containing moieties on inhibition of cPLA2α and fatty acid amide hydrolase as well as on metabolic stability in rat liver S9 fractions was investigated. As a result of these structure-activity relationship studies it was found that the ether oxygen is of great importance for enzyme inhibitory potency. Replacement by sulfur led to an about 100-fold decrease of enzyme inhibition, nitrogen and substituted nitrogen atoms at this position even resulted in inactivity of the compounds. The effect of the structural variations performed on metabolic stability of the important ketone pharmacophore was partly different in the two series of compounds. While introduction of SO and SO2 significantly increased stability of the ketone against reduction in case of the indole-5-carboxylic acid 3, it had no effect in case of the benzotriazole 4. Further analysis of the metabolism of 3 and 4 in rat liver S9 fractions revealed that the major metabolite of 3 was the alcohol 53 formed by reduction of the keto group. In contrast, in case of 4 beside keto reduction an excessive hydroxylation of the terminal phenoxy group occurred leading to the dihydroxy compound 50. Experiments with enzyme inhibitors showed that the phenylhydroxylation of 4 was catalyzed by tranylcypromine sensitive cytochrome P450 isoforms, while the reduction of the ketone function of 3 and 4 was mainly caused by cytosolic short chain dehydrogenases

  1. Mechanism of fluorescence quenching of tyrosine derivatives by amide group

    NASA Astrophysics Data System (ADS)

    Wiczk, Wiesław; Rzeska, Alicja; Łukomska, Joanna; Stachowiak, Krystyna; Karolczak, Jerzy; Malicka, Joanna; Łankiewicz, Leszek

    2001-06-01

    The difference between fluorescence lifetimes of the following amino acids: phenylalanine (Phe), tyrosine (Tyr), ( O-methyl)tyrosine (Tyr(Me)), (3-hydroxy)tyrosine (Dopa), (3,4-dimethoxy)phenylalanine (Dopa(Me) 2) and their amides was used to testify the mechanism of fluorescence quenching of aromatic amino acids by the amide group. On the basis of the Marcus theory of photoinduced electron transfer parabolic relationships between ln kET and ionization potentials reduced by energy of excitation ( IP-E ∗0,0) for the above-mentioned amino acids were obtained. This finding indicates the occurrence of photoinduced electron transfer from the excited chromophore group to the amide group.

  2. Possible evidence of amide bond formation between sinapinic acid and lysine-containing bacterial proteins by matrix-assisted laser desorption/ionization (MALDI) at 355 nm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously reported the apparent formation of matrix adducts of 3,5-dimethoxy-4-hydroxy-cinnamic acid (sinapinic acid or SA) via covalent attachment to disulfide bond-containing proteins (HdeA, HdeB and YbgS) from bacterial cell lysates ionized by matrix-assisted laser desorption/ionization (MALD...

  3. Synthesis, spectroscopic, thermal and structural elucidation of 5-amino-2-methoxypyridine ester amide of squaric acid ethyl ester: A new material with an infinite pseudo-layered structure and manifested NLO application

    NASA Astrophysics Data System (ADS)

    Kolev, Tsonko; Koleva, Bojidarka B.; Spassov, Tony; Cherneva, Emilya; Spiteller, Michael; Mayer-Figge, Heike; Sheldrick, William S.

    2008-03-01

    The novel squaric acid derivative, 5-amino-2-methoxypyridin ester amide of squaric acid ethyl ester with second order NLO application in solution and in the bulk has been synthesized and is structure and properties elucidated in detail spectroscopic, thermally and structurally, using single crystal X-ray diffraction, linear-polarized solid state IR-spectroscopy, UV-spectroscopy, and TGA, DSC, DTA, MS and SHG methods. Quantum chemical calculations were used for obtain in the electronic structure, vibrational data and NLO properties. At room temperature the studied compound crystallizes in the noncentrosymmetric space group Cc and exhibits a pseudo-layer structure (solid phase 1) with molecules linked by NH⋯O dbnd C intermolecular hydrogen bonds with length of 2.955 Å and NH⋯O angle of 153.41°, respectively. At 200 °C a phase transition is observed, with the solid phase 2 exhibiting new intermolecular NH⋯N interactions, as elucidated by IR-spectroscopy and thermal analysis. The obtained large powder SHG efficiency of 609 times urea proves the NLO application of studied compound in the bulk.

  4. Fatty acid composition including cis-9, trans-11 CLA of cooked ground lamb

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little information is available on effect of cooking on beneficial fatty acids such as conjugated linoleic acid (CLA) and n-3 polyunsaturated fatty acids (PUFA). The objective of this study was to examine impact of cooking on the FA composition of ground lamb of two different muscles. Samples were p...

  5. Tandem dissolution of UO 3 in amide-based acidic ionic liquid and in situ electrodeposition of UO 2 with regeneration of the ionic liquid: a closed cycle

    DOE PAGES

    Wanigasekara, Eranda; Freiderich, John W.; Sun, Xiao-Guang; Meisner, Roberta A.; Luo, Huimin; Delmau, Lætitia H.; Dai, Sheng; Moyer, Bruce A.

    2016-05-19

    A closed cycle is demonstrated for the tandem dissolution and electroreduction of UO3 to UO2 with regeneration of the acidic ionic liquid. The dissolution is achieved by use of the acidic ionic liquid N,N-dimethylacetimidium bis(trifluoromethanesulfonimide) in 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonimide) serving as the diluent. Bulk electrolysis performed at 1.0 V vs. Ag reference yields a dark brown-black uranium deposit (UO2) on the cathode. Anodic oxidation of water in the presence of dimethylacetamide regenerates the acidic ionic liquid. We have demonstrated the individual steps in the cycle together with a sequential dissolution, electroreduction, and regeneration cycle.

  6. Pharmacokinetics and metabolism studies on the glucagon-like peptide-1 (GLP-1)-derived metabolite GLP-1(9-36)amide in male Beagle dogs.

    PubMed

    Eng, Heather; Sharma, Raman; McDonald, Thomas S; Landis, Margaret S; Stevens, Benjamin D; Kalgutkar, Amit S

    2014-09-01

    Glucagon-like peptide-1 (GLP-1)(7-36)amide is a 30-amino acid peptide hormone that is secreted from intestinal enteroendocrine L-cells in response to nutrients. GLP-1(7-36)amide possesses potent insulinotropic actions in the augmentation of glucose-dependent insulin secretion. GLP-1(7-36)amide is rapidly metabolized by dipeptidyl peptidase-IV to yield GLP-1(9-36)amide as the principal metabolite. Contrary to the earlier notion that peptide cleavage products of native GLP-1(7-36)amide [including GLP-1(9-36)amide] are pharmacologically inactive, recent studies have demonstrated cardioprotective and insulinomimetic effects with GLP-1(9-36)amide in mice, dogs and humans. In the present work, in vitro metabolism and pharmacokinetic properties of GLP-1(9-36)amide have been characterized in dogs, since this preclinical species has been used as an animal model to demonstrate the in vivo vasodilatory and cardioprotective effects of GLP-1(9-36)amide. A liquid chromatography tandem mass spectrometry assay was developed for the quantitation of the intact peptide in hepatocyte incubations as opposed to a previously reported enzyme-linked immunosorbent assay. Although GLP-1(9-36)amide was resistant to proteolytic cleavage in dog plasma and bovine serum albumin (t1/2>240 min), the peptide was rapidly metabolized in dog hepatocytes with a t1/2 of 110 min. Metabolite identification studies in dog hepatocytes revealed a variety of N-terminus cleavage products, most of which, have also been observed in human and mouse hepatocytes. Proteolysis at the C-terminus was not observed in GLP-1(9-36)amide. Following the administration of a single intravenous bolus dose (20 µg/kg) to male Beagle dogs, GLP-1(9-36)amide exhibited a mean plasma clearance of 15 ml/min/kg and a low steady state distribution volume of 0.05 l/kg, which translated into a short elimination half life of 0.05 h. Following subcutaneous administration of GLP-1(9-36)amide at 50 µg/kg, systemic exposure of

  7. Influence of Fatty Acid Precursors, Including Food Preservatives, on the Growth and Fatty Acid Composition of Listeria monocytogenes at 37 and 10°C ▿

    PubMed Central

    Julotok, Mudcharee; Singh, Atul K.; Gatto, Craig; Wilkinson, Brian J.

    2010-01-01

    Listeria monocytogenes is a food-borne pathogen that grows at refrigeration temperatures and increases its content of anteiso-C15:0 fatty acid, which is believed to be a homeoviscous adaptation to ensure membrane fluidity, at these temperatures. As a possible novel approach for control of the growth of the organism, the influences of various fatty acid precursors, including branched-chain amino acids and branched- and straight-chain carboxylic acids, some of which are also well-established food preservatives, on the growth and fatty acid composition of the organism at 37°C and 10°C were studied in order to investigate whether the organism could be made to synthesize fatty acids that would result in impaired growth at low temperatures. The results indicate that the fatty acid composition of L. monocytogenes could be modulated by the feeding of branched-chain amino acid, C4, C5, and C6 branched-chain carboxylic acid, and C3 and C4 straight-chain carboxylic acid fatty acid precursors, but the growth-inhibitory effects of several preservatives were independent of effects on fatty acid composition, which were minor in the case of preservatives metabolized via acetyl coenzyme A. The ability of a precursor to modify fatty acid composition was probably a reflection of the substrate specificities of the first enzyme, FabH, in the condensation of primers of fatty acid biosynthesis with malonyl acyl carrier protein. PMID:20048057

  8. Influence of fatty acid precursors, including food preservatives, on the growth and fatty acid composition of Listeria monocytogenes at 37 and 10degreesC.

    PubMed

    Julotok, Mudcharee; Singh, Atul K; Gatto, Craig; Wilkinson, Brian J

    2010-03-01

    Listeria monocytogenes is a food-borne pathogen that grows at refrigeration temperatures and increases its content of anteiso-C(15:0) fatty acid, which is believed to be a homeoviscous adaptation to ensure membrane fluidity, at these temperatures. As a possible novel approach for control of the growth of the organism, the influences of various fatty acid precursors, including branched-chain amino acids and branched- and straight-chain carboxylic acids, some of which are also well-established food preservatives, on the growth and fatty acid composition of the organism at 37 degrees C and 10 degrees C were studied in order to investigate whether the organism could be made to synthesize fatty acids that would result in impaired growth at low temperatures. The results indicate that the fatty acid composition of L. monocytogenes could be modulated by the feeding of branched-chain amino acid, C(4), C(5), and C(6) branched-chain carboxylic acid, and C(3) and C(4) straight-chain carboxylic acid fatty acid precursors, but the growth-inhibitory effects of several preservatives were independent of effects on fatty acid composition, which were minor in the case of preservatives metabolized via acetyl coenzyme A. The ability of a precursor to modify fatty acid composition was probably a reflection of the substrate specificities of the first enzyme, FabH, in the condensation of primers of fatty acid biosynthesis with malonyl acyl carrier protein.

  9. Succinic acid monoethyl ester, a novel insulinotropic agent: effect on lipid composition and lipid peroxidation in streptozotocin-nicotin-amide induced type 2 diabetic rats.

    PubMed

    Saravanan, Ramalingam; Pari, Leelavinothan

    2007-02-01

    Succinic acid monoethyl ester (EMS) is recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. Oxidative stress has been suggested to be a contributory factor in the development and complications of diabetes. In the present study the effect of EMS and Metformin on plasma glucose, insulin, serum and tissue lipid profile, lipoproteins and lipid peroxidation in streptozotocin-nicotinamide induced type 2 diabetic model was investigated. The carboxylic nutrient EMS was administered intraperitonially (8 micromol/g body weight) to streptozotocin diabetic rats for 30 days. The levels of thiobarbituric acid reactive substances (TBARS) and hydroperoxides in liver and kidney and serum and tissue lipids [cholesterol, triglycerides, phospholipids and free fatty acids] and very low density lipoprotein-cholesterol (VLDL-C) and low density lipoprotein-cholesterol (LDL-C), were significantly increased in diabetic rats, whereas the levels of high-density lipoprotein-cholesterol (HDL-C) and antiatherogenic index (AAI) (ratio of HDL to total cholesterol) were significantly decreased. The effect of EMS was compared with metformin, a reference drug. Treatment with EMS and metformin resulted in a significant reduction of plasma glucose with increase plasma insulin in diabetic rats. EMS also resulted in a significant decrease in serum and tissue lipids and lipid peroxidation products. These biochemical observations were supplemented by histopathological examination of liver and kidney section. Our results suggest the possible antihyperlipidemic and antiperoxidative effect of EMS apart from its antidiabetic effect. PMID:17006620

  10. Fatty acid-releasing activities in Sinorhizobium meliloti include unusual diacylglycerol lipase

    PubMed Central

    Sahonero-Canavesi, Diana X.; Sohlenkamp, Christian; Sandoval-Calderón, Mario; Lamsa, Anne; Pogliano, Kit; López-Lara, Isabel M.; Geiger, Otto

    2016-01-01

    Summary Phospholipids are well known for their membrane forming properties and thereby delimit any cell from the exterior world. In addition, membrane phospholipids can act as precursors for signals and other biomolecules during their turnover. Little is known about phospholipid signalling, turnover and remodelling in bacteria. Recently, we showed that a FadD-deficient mutant of Sinorhizobium meliloti, unable to convert free fatty acids to their coenzyme A derivatives, accumulates free fatty acids during the stationary phase of growth. Enzymatic activities responsible for the generation of these free fatty acids were unknown in rhizobia. Searching the genome of S. meliloti, we identified a potential lysophospholipase (SMc04041) and two predicted patatin-like phospholipases A (SMc00930, SMc01003). Although SMc00930 as well as SMc01003 contribute to the release of free fatty acids in S. meliloti, neither one can use phospholipids as substrates. Here we show that SMc01003 converts diacylglycerol to monoacylglycerol and a fatty acid, and that monoacylglycerol can be further degraded by SMc01003 to another fatty acid and glycerol. A SMc01003-deficient mutant of S. meliloti transiently accumulates diacylglycerol, suggesting that SMc01003 also acts as diacylglycerol lipase (DglA) in its native background. Expression of the DglA lipase in Escherichia coli causes lysis of cells in stationary phase of growth. PMID:25711932

  11. Fatty acid-releasing activities in Sinorhizobium meliloti include unusual diacylglycerol lipase.

    PubMed

    Sahonero-Canavesi, Diana X; Sohlenkamp, Christian; Sandoval-Calderón, Mario; Lamsa, Anne; Pogliano, Kit; López-Lara, Isabel M; Geiger, Otto

    2015-09-01

    Phospholipids are well known for their membrane-forming properties and thereby delimit any cell from the exterior world. In addition, membrane phospholipids can act as precursors for signals and other biomolecules during their turnover. Little is known about phospholipid signalling, turnover and remodelling in bacteria. Recently, we showed that a FadD-deficient mutant of Sinorhizobium meliloti, unable to convert free fatty acids to their coenzyme A derivatives, accumulates free fatty acids during the stationary phase of growth. Enzymatic activities responsible for the generation of these free fatty acids were unknown in rhizobia. Searching the genome of S. meliloti, we identified a potential lysophospholipase (SMc04041) and two predicted patatin-like phospholipases A (SMc00930, SMc01003). Although SMc00930 as well as SMc01003 contribute to the release of free fatty acids in S. meliloti, neither one can use phospholipids as substrates. Here we show that SMc01003 converts diacylglycerol to monoacylglycerol and a fatty acid, and that monoacylglycerol can be further degraded by SMc01003 to another fatty acid and glycerol. A SMc01003-deficient mutant of S. meliloti transiently accumulates diacylglycerol, suggesting that SMc01003 also acts as diacylglycerol lipase (DglA) in its native background. Expression of the DglA lipase in Escherichia coli causes lysis of cells in stationary phase of growth.

  12. Intrinsic propensities of amino acid residues in GxG peptides inferred from amide I' band profiles and NMR scalar coupling constants.

    PubMed

    Hagarman, Andrew; Measey, Thomas J; Mathieu, Daniel; Schwalbe, Harald; Schweitzer-Stenner, Reinhard

    2010-01-20

    A reliable intrinsic propensity scale of amino acid residues is indispensable for an assessment of how local conformational distributions in the unfolded state can affect the folding of peptides and proteins. Short host-guest peptides, such as GxG tripeptides, are suitable tools for probing such propensities. To explore the conformational distributions sampled by the central amino acid residue in these motifs, we combined vibrational (IR, Raman, and VCD) with NMR spectroscopy. The data were analyzed in terms of a superposition of two-dimensional Gaussian distribution functions in the Ramachandran space pertaining to subensembles of polyproline II, beta-strand, right- and left-handed helical, and gamma-turn-like conformations. The intrinsic propensities of eight amino acid residues (x = A, V, F, L, S, E, K, and M) in GxG peptides were determined as mole fractions of these subensembles. Our results show that alanine adopts primarily (approximately 80%) a PPII-like conformation, while valine and phenylalanine were found to sample PPII and beta-strand-like conformations equally. The centers of the respective beta-strand distributions generally do not coincide with canonical values of dihedral angles of residues in parallel or antiparallel beta-strands. In fact, the distributions for most residues found in the beta-region significantly overlap the PPII-region. A comparison with earlier reported results for trivaline reveals that the terminal valines increase the beta-strand propensity of the central valine residue even further. Of the remaining investigated amino acids, methionine preferred PPII the most (0.64), and E, S, L, and K exhibit moderate (0.56-0.45) PPII propensities. Residues V, F, S, E, and L sample, to a significant extent, a region between the canonical PPII and (antiparallel) beta-strand conformations. This region coincides with the sampling reported for L and V using theoretical predictions (Tran et al. Biochemistry 2005, 44, 11369). The distributions of

  13. Altering the fatty acids in milk fat by including canola seed in dairy cattle diets.

    PubMed

    Chichlowski, M W; Schroeder, J W; Park, C S; Keller, W L; Schimek, D E

    2005-09-01

    The objective was to evaluate the effects of feeding ground canola seed on the fatty acid profile, yield, and composition of milk from dairy cows. Twenty-four multiparous Holstein cows (548.3 +/- 11.9 kg body weight and 28 +/- 9 d in lactation) were randomly assigned to 1 of 2 treatments: Control (CON) or ground canola seed treatment (GCS) with 14% [of diet dry matter (DM)] of the total ration as ground canola seed containing 34% lipid. Diets contained 20% crude protein, but varied in net energy as a result of fat content differences of 2.5% and 6.4% (DM) for CON and GCS, respectively. Diets were composed of corn, corn silage, alfalfa (50:50 ground hay and haylage, DM basis), soybean and blood meal, and vitamins and minerals. Mechanically extruded canola meal was used in the CON diet to adjust for the protein from canola seed in the GCS diet. Cows were housed in tie-stalls and fed and milked twice daily for 10 wk. The inclusion of ground canola seed did not alter DM intake, weight gain, or body condition score of cows. Milk fat from GCS cows had greater proportions of long-chain fatty acids (> or = 18 carbons) and a lower ratio of n-6 to n-3 fatty acids. Feeding GCS reduced the proportion of short- and medium-chain fatty acids. Milk fat from cows fed GCS had a greater proportion of vaccenic acid and tended to have a higher proportion of cis-9,trans-11 conjugated linoleic acid. Actual and 3.5% fat-corrected milk yields were similar between treatments. The milk fat and protein percentages were lower for GCS cows, but total yield of these components was similar between treatments. Milk urea nitrogen was lower and serum urea nitrogen tended to be lower in cows fed canola seed. Serum glucose, insulin, and nonesterified fatty acids were not altered, but serum triglycerides were higher in GCS cows. Ammonia and total volatile fatty acids tended to be lower in ruminal fluid from GCS cows; rumen pH was unchanged. Feeding canola seed to lactating dairy cows resulted in milk

  14. Amidation of Bioactive Peptides: The Structure of the Lyase Domain of the Amidating Enzyme

    SciTech Connect

    Chufan, E.; De, M; Eipper, B; Mains, R; Amzel, L

    2009-01-01

    Many neuropeptides and peptide hormones require amidation of their carboxy terminal for full biological activity. The enzyme peptidyl-{alpha}-hydroxyglycine {alpha}-amidating lyase (PAL; EC 4.3.2.5) catalyzes the second and last step of this reaction, N-dealkylation of the peptidyl-{alpha}-hydroxyglycine to generate the {alpha}-amidated peptide and glyoxylate. Here we report the X-ray crystal structure of the PAL catalytic core (PALcc) alone and in complex with the nonpeptidic substrate {alpha}-hydroxyhippuric acid. The structures show that PAL folds as a six-bladed {Beta}-propeller. The active site is formed by a Zn(II) ion coordinated by three histidine residues; the substrate binds to this site with its {alpha}-hydroxyl group coordinated to the Zn(II) ion. The structures also reveal a tyrosine residue (Tyr{sup 654}) at the active site as the catalytic base for hydroxyl deprotonation, an unusual role for tyrosine. A reaction mechanism is proposed based on this structural data and validated by biochemical analysis of site-directed PALcc mutants.

  15. Preparation of a new chiral stationary phase for HPLC based on the (R)- 1-phenyl-2-(4-methylphenyl)ethylamine amide derivative of (S)-valine and 2-chloro-3,5-dinitrobenzoic acid: enantioseparation of amino acid derivatives and pyrethroid insecticides.

    PubMed

    Tan, Xulin; Hou, Shicong; Jiang, Jingli; Wang, Min

    2007-08-01

    A novel chiral stationary phase (CSP) for HPLC was prepared by bonding (R)-1-phenyl-2-(4-methylphenyl)ethylamine amide derivative of (S)-valine to aminopropyl silica gel through a 2-amino-3,5-dinitro-1-carboxamido-benzene unit. The CSP was used for the separation of some amino acid derivatives and pyrethroid insecticides by chiral HPLC. Satisfactory baseline separation required optimization of the variables of mobile phase composition. Use of dichloromethane as modifier in the mobile phase gave baseline separations of amino acid derivatives. The two enantiomers of fenpropathrin and four stereoisomers of fenvalerate were baseline separated using hexane-dichloromethane-ethanol as mobile phase. The results show that the enantioselectivity of the new CSP is better than Pirkle type 1-A column for these compounds. Only partial separations were observed for the stereoisomers of cypermethrin and cyfluthrin, which gave even and eight peaks, respectively.

  16. Case Studies in Systems Chemistry. Final Report. [Includes Complete Case Study, Carboxylic Acid Equilibria

    ERIC Educational Resources Information Center

    Fleck, George

    This publication was produced as a teaching tool for college chemistry. The book is a text for a computer-based unit on the chemistry of acid-base titrations, and is designed for use with FORTRAN or BASIC computer systems, and with a programmable electronic calculator, in a variety of educational settings. The text attempts to present computer…

  17. Antibiosis of some lactic acid bacteria including Lactobacillus acidophilus toward Listeria monocytogenes.

    PubMed

    Raccach, M; McGrath, R; Daftarian, H

    1989-08-01

    Eleven strains of lactic acid bacteria were tested by the 'spot' on the 'lawn' method for their antagonistic activity against four strains of Listeria monocytogenes. Four out of the five strains of lactic acid bacteria most antagonistic toward the pathogen were those cultures known to produce bacteriocins. Four other strains of lactic acid bacteria were not antagonistic against Listeria by this method. Seventeen inhibition zones of the pathogen were obtained at 25 degrees C as compared to 10 at 32 degrees C. Lactobacillus acidophilus strains NU-A and 88, growing in the presence of L. monocytogenes in milk prevented the latter from attaining populations it would have in pure culture (P less than 0.01). 10(1.4)-10(3.5) lower numbers were noted. L. acidophilus in most cases exhibited a bacteriostatic effect toward the pathogen except for strain 88 which appeared to have a bactericidal effect (P less than 0.01) against Listeria strain OH. The lactobacilli reduced the pH of the milk to 4.7 over a 24 h period, showing that acid played a role in the observed antibiosis.

  18. Kinetic model of water disinfection using peracetic acid including synergistic effects.

    PubMed

    Flores, Marina J; Brandi, Rodolfo J; Cassano, Alberto E; Labas, Marisol D

    2016-01-01

    The disinfection efficiencies of a commercial mixture of peracetic acid against Escherichia coli were studied in laboratory scale experiments. The joint and separate action of two disinfectant agents, hydrogen peroxide and peracetic acid, were evaluated in order to observe synergistic effects. A kinetic model for each component of the mixture and for the commercial mixture was proposed. Through simple mathematical equations, the model describes different stages of attack by disinfectants during the inactivation process. Based on the experiments and the kinetic parameters obtained, it could be established that the efficiency of hydrogen peroxide was much lower than that of peracetic acid alone. However, the contribution of hydrogen peroxide was very important in the commercial mixture. It should be noted that this improvement occurred only after peracetic acid had initiated the attack on the cell. This synergistic effect was successfully explained by the proposed scheme and was verified by experimental results. Besides providing a clearer mechanistic understanding of water disinfection, such models may improve our ability to design reactors. PMID:26819382

  19. Cleavage kinetics and anchor linked intermediates in solid phase peptide amide synthesis.

    PubMed

    Dürr, H; Beck-Sickinger, A G; Schnorrenberg, G; Rapp, W; Jung, G

    1991-08-01

    Kinetics and cleavage conditions of peptide amide synthesis were studied using the anchor molecules 5-(4'-aminomethyl-3',5'-dimethoxyphenoxy)valeric acid (4-ADPV-OH) and 5-(2'-aminomethyl-3'-5'-dimethoxyphenoxy) valeric acid (2-ADPV-OH). Unexpectedly the anchor amide alanyl-4-ADPV-NH2 was isolated and characterized as an intermediate during the cleavage with trifluoroacetic acid (TFA) of alanyl-4-ADPV-alanyl-aminomethyl-polystyrene to yield the alanine amide. As a matter of fact the NH--CH alpha bond of the alanyl spacer has to be cleaved to form this intermediate. Using TFA-dichloromethane (1:9) alanyl-4-ADPV-NH2 was obtained as a cleavage product in 50% yield within 60 min, whereas the isomeric alanyl-2-ADPV-NH2 was formed more slowly under these mild conditions. At high TFA concentration no difference between the 2- and 4-ADPV anchor was observed in the rate of formation of the free alanine amide. The presence of tryptophan amide in the cleavage mixture resulted in an anchor alkylated tryptophan amide, which remains stable in acidic solution but disappears rapidly in the presence of the resin. A low TFA/high TFA cleavage procedure is recommended for peptide amid synthesis applying the ADPV anchor.

  20. Synthesis of an Acyltrifluoroborate and its Fusion with Azides to Form Amides

    PubMed Central

    Raushel, Jessica; Ellis, Noel M.

    2010-01-01

    A uniquely stable acyl potassium trifluoroborate, potassium (2-phenylacetyl) trifluoroborate, has been synthesized and isolated. In the presence of an activating Lewis acid, this reagent reacts with azides to form amides in good yields. PMID:20481486

  1. Reversed-phase high-performance liquid chromatographic separation of diastereomers of (R,S)-mexiletine prepared by microwave irradiation with four new chiral derivatizing reagents based on trichloro-s-triazine having amino acids as chiral auxiliaries and 10 others having amino acid amides.

    PubMed

    Bhushan, Ravi; Dixit, Shuchi

    2010-12-01

    A new series of chiral derivatizing reagents (CDRs) consisting of four dichloro-s-triazine reagents was synthesized by nucleophilic substitution of one chlorine atom in trichloro-s-triazine with amino acids, namely L-Leu, D-Phg, L-Val and L-Ala as chiral auxiliaries. Two other sets of CDRs consisting of four dichloro-s-triazine (DCT) and six monochloro-s-triazine (MCT) reagents were also prepared by nucleophilic substitution of chlorine atom(s) with different amino acid amides as chiral auxiliaries in trichloro-s-triazine and its 6-methoxy derivative, respectively. These 14 CDRs were used for the synthesis of diastereomers of (R,S)-mexiletine under microwave irradiation (i.e. 60s and 90 s at 85% power (of 800 W) using DCT and MCT reagents, respectively), which were resolved by reversed-phase high-performance liquid chromatography using C18 column and gradient eluting mixtures of methanol with aqueous trifluoroacetic acid (TFA) with UV detection at 230 nm. The resolution (R(s)), difference between retention times of resolved diastereomers (Δt) and retention factors (k) obtained for the three sets of diastereomers were compared among themselves and among the three groups. Explanations have been offered for longer retention times and better resolution of diastereomers prepared with DCT reagents in comparison of their MCT counterparts and, for the influence of hydrophobicity of the side chain R of the amino acid in the CDRs on retention times and resolution. The newly synthesized CDRs were observed to be superior as compared to their amide counterparts in terms of providing better resolution and cost effectiveness. The method was validated for limit of detection, linearity, accuracy and precision. PMID:21035811

  2. Car Parrinello molecular dynamics simulation of base-catalyzed amide hydrolysis in aqueous solution

    NASA Astrophysics Data System (ADS)

    Zahn, Dirk

    2004-01-01

    The base catalyzed hydrolysis of N-methylacetamide is elucidated by means of Car-Parrinello simulation. The process is investigated in aqueous solution, including a quantum treatment of all electronic degrees of freedom. The rate-determining step is the attack of a hydroxide ion on the amide carbon atom. This is followed by protonation of the nitrogen atom. The final dissociation may occur via two different pathways: (i) dissociation into an amine and a carboxylic acid and (ii) oxygen deprotonation and dissociation into an amine and a carboxyl anion. The later pathway was found to be strongly favored.

  3. Polymer Amide as an Early Topology

    PubMed Central

    McGeoch, Julie E. M.; McGeoch, Malcolm W.

    2014-01-01

    Hydrophobic polymer amide (HPA) could have been one of the first normal density materials to accrete in space. We present ab initio calculations of the energetics of amino acid polymerization via gas phase collisions. The initial hydrogen-bonded di-peptide is sufficiently stable to proceed in many cases via a transition state into a di-peptide with an associated bound water molecule of condensation. The energetics of polymerization are only favorable when the water remains bound. Further polymerization leads to a hydrophobic surface that is phase-separated from, but hydrogen bonded to, a small bulk water complex. The kinetics of the collision and subsequent polymerization are discussed for the low-density conditions of a molecular cloud. This polymer in the gas phase has the properties to make a topology, viz. hydrophobicity allowing phase separation from bulk water, capability to withstand large temperature ranges, versatility of form and charge separation. Its flexible tetrahedral carbon atoms that alternate with more rigid amide groups allow it to deform and reform in hazardous conditions and its density of hydrogen bonds provides adhesion that would support accretion to it of silicon and metal elements to form a stellar dust material. PMID:25048204

  4. Cellular Inhibition of Checkpoint Kinase 2 (Chk2) and Potentiation of Camptothecins and Radiation by the Novel Chk2 Inhibitor PV1019 [7-Nitro-1H-indole-2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]-phenyl}-amide

    SciTech Connect

    Jobson, Andrew G.; Lountos, George T.; Lorenzi, Philip L.; Llamas, Jenny; Connelly, John; Cerna, David; Tropea, Joseph E.; Onda, Akikazu; Zoppoli, Gabriele; Kondapaka, Sudhir; Zhang, Guangtao; Caplen, Natasha J.; Cardellina, II, John H.; Yoo, Stephen S.; Monks, Anne; Self, Christopher; Waugh, David S.; Shoemaker, Robert H.; Pommier, Yves

    2010-04-05

    Chk2 is a checkpoint kinase involved in the ataxia telangiectasia mutated pathway, which is activated by genomic instability and DNA damage, leading to either cell death (apoptosis) or cell cycle arrest. Chk2 provides an unexplored therapeutic target against cancer cells. We recently reported 4,4'-diacetyldiphenylurea-bis(guanylhydrazone) (NSC 109555) as a novel chemotype Chk2 inhibitor. We have now synthesized a derivative of NSC 109555, PV1019 (NSC 744039) [7-nitro-1H-indole-2-carboxylic acid {l_brace}4-[1-(guanidinohydrazone)-ethyl]-phenyl{r_brace}-amide], which is a selective submicromolar inhibitor of Chk2 in vitro. The cocrystal structure of PV1019 bound in the ATP binding pocket of Chk2 confirmed enzymatic/biochemical observations that PV1019 acts as a competitive inhibitor of Chk2 with respect to ATP. PV1019 was found to inhibit Chk2 in cells. It inhibits Chk2 autophosphorylation (which represents the cellular kinase activation of Chk2), Cdc25C phosphorylation, and HDMX degradation in response to DNA damage. PV1019 also protects normal mouse thymocytes against ionizing radiation-induced apoptosis, and it shows synergistic antiproliferative activity with topotecan, camptothecin, and radiation in human tumor cell lines. We also show that PV1019 and Chk2 small interfering RNAs can exert antiproliferative activity themselves in the cancer cells with high Chk2 expression in the NCI-60 screen. These data indicate that PV1019 is a potent and selective inhibitor of Chk2 with chemotherapeutic and radiosensitization potential.

  5. N-(3,4-Dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[(11)C]methylphenyl)thiazol-2-yl]-1-carboxamide: A promising positron emission tomography ligand for fatty acid amide hydrolase.

    PubMed

    Shimoda, Yoko; Fujinaga, Masayuki; Hatori, Akiko; Yui, Joji; Zhang, Yiding; Nengaki, Nobuki; Kurihara, Yusuke; Yamasaki, Tomoteru; Xie, Lin; Kumata, Katsushi; Ishii, Hideki; Zhang, Ming-Rong

    2016-02-15

    To visualize fatty acid amide hydrolase (FAAH) in brain in vivo, we developed a novel positron emission tomography (PET) ligand N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[(11)C]methylphenyl)thiazol-2-yl]-1-carboxamide ([(11)C]DFMC, [(11)C]1). DFMC (1) was shown to have high binding affinity (IC50: 6.1nM) for FAAH. [(11)C]1 was synthesized by C-(11)C coupling reaction of arylboronic ester 2 with [(11)C]methyl iodide in the presence of Pd catalyst. At the end of synthesis, [(11)C]1 was obtained with a radiochemical yield of 20±10% (based on [(11)C]CO2, decay-corrected, n=5) and specific activity of 48-166GBq/μmol. After the injection of [(11)C]1 in mice, high uptake of radioactivity (>2% ID/g) was distributed in the lung, liver, kidney, and brain, organs with high FAAH expression. PET images of rat brains for [(11)C]1 revealed high uptakes in the cerebellar nucleus (SUV=2.4) and frontal cortex (SUV=2.0), two known brain regions with high FAAH expression. Pretreatment with the FAAH-selective inhibitor URB597 reduced the brain uptake. Higher than 90% of the total radioactivity in the rat brain was irreversible at 30min after the radioligand injection. The present results indicate that [(11)C]1 is a promising PET ligand for imaging of FAAH in living brain. PMID:26740152

  6. Inhibition of fatty acid amide hydrolase and cyclooxygenase-2 increases levels of endocannabinoid related molecules and produces analgesia via peroxisome proliferator-activated receptor-alpha in a model of inflammatory pain.

    PubMed

    Jhaveri, Maulik D; Richardson, Denise; Robinson, Ian; Garle, Michael J; Patel, Annie; Sun, Yan; Sagar, Devi R; Bennett, Andrew J; Alexander, Stephen P H; Kendall, David A; Barrett, David A; Chapman, Victoria

    2008-07-01

    The antinociceptive effects of the endocannabinoids (ECs) are enhanced by inhibiting catabolic enzymes such as fatty acid amide hydrolase (FAAH). The physiological relevance of the metabolism of ECs by other pathways, such as cyclooxygenase-2 (COX2) is less clear. To address this question we compared the effects of local inhibition of FAAH versus COX2 (URB597 and nimesulide, respectively) on inflammatory hyperalgesia and levels of endocannabinoids and related molecules in the hindpaw. Inflammatory hyperalgesia was measured following intraplantar injection of carrageenan. Effects of intraplantar injection of URB597 (25 microg and 100 microg) or nimesulide (50 microg) on hyperalgesia and hindpaw levels of anandamide (AEA), 2-arachidonoylglycerol (2AG) and N-palmitoylethanolamine (PEA) were determined. Although both doses of URB597 increased levels of AEA and 2AG in the carrageenan inflamed hindpaw, only the lower dose of URB597 attenuated hyperalgesia (P<0.05). Nimesulide attenuated both hyperalgesia and hindpaw oedema (P<0.001, P<0.01, respectively) and increased levels of PEA (P<0.05) in the hindpaw. Since both AEA and PEA are ligands for peroxisome proliferator-activated receptor-alpha (PPARalpha), the effects of the PPARalpha antagonist GW6471 on nimesulide- and URB597-mediated effects were studied. GW6471, but not a PPARgamma antagonist, blocked the inhibitory effects of nimesulide and URB597 on hyperalgesia. Our data suggest that both COX2 and FAAH play a role in the metabolism of endocannabinoids and related molecules. The finding that PPARalpha antagonism blocked the inhibitory effects of nimesulide and URB597 suggests that PPARalpha contributes to their antinociceptive effects in the carrageenan model of inflammatory hyperalgesia.

  7. Pharmacology and antitussive efficacy of 4-(3-trifluoromethyl-pyridin-2-yl)-piperazine-1-carboxylic acid (5-trifluoromethyl-pyridin-2-yl)-amide (JNJ17203212), a transient receptor potential vanilloid 1 antagonist in guinea pigs.

    PubMed

    Bhattacharya, Anindya; Scott, Brian P; Nasser, Nadia; Ao, Hong; Maher, Michael P; Dubin, Adrienne E; Swanson, Devin M; Shankley, Nigel P; Wickenden, Alan D; Chaplan, Sandra R

    2007-11-01

    Transient receptor potential vanilloid 1 (TRPV1) plays an integral role in modulating the cough reflex, and it is an attractive antitussive drug target. The purpose of this study was to characterize a TRPV1 antagonist, 4-(3-trifluoromethyl-pyridin-2-yl)-piperazine-1-carboxylic acid (5-trifluoromethyl-pyridin-2-yl)-amide (JNJ17203212), against the guinea pig TRPV1 receptor in vitro followed by a proof-of-principle study in an acid-induced model of cough. The affinity of JNJ17203212 for the recombinant guinea pig TRPV1 receptor was estimated by radioligand binding, and it was functionally characterized by antagonism of low-pH and capsaicin-induced activation of the ion channel (fluorometric imaging plate reader and electrophysiology). The nature of antagonism was further tested against the native channel in isolated guinea pig tracheal rings. Following pharmacokinetic characterization of JNJ17203212 in guinea pigs, pharmacodynamic and efficacy studies were undertaken to establish the antitussive efficacy of the TRPV1 antagonist. The pK(i) of JNJ17203212 for recombinant guinea pig TRPV1 was 7.14 +/- 0.06. JNJ17203212 inhibited both pH (pIC(50) of 7.23 +/- 0.05) and capsaicin (pIC(50) of 6.32 +/- 0.06)-induced channel activation. In whole-cell patch clamp, the pIC(50) for inhibition of guinea pig TRPV1 was 7.3 +/- 0.01. JNJ17203212 demonstrated surmountable antagonism in isolated trachea, with a pK(B) value of 6.2 +/- 0.1. Intraperitoneal administration of 20 mg/kg JNJ17203212 achieved a maximal plasma exposure of 8.0 +/- 0.4 microM, and it attenuated capsaicin evoked coughs with similar efficacy to codeine (25 mg/kg). Last, JNJ17203212 dose-dependently produced antitussive efficacy in citric acid-induced experimental cough in guinea pigs. Our data provide preclinical support for developing TRPV1 antagonists for the treatment of cough.

  8. Synthesis of amide-functionalized cellulose esters by olefin cross-metathesis.

    PubMed

    Meng, Xiangtao; Edgar, Kevin J

    2015-11-01

    Cellulose esters with amide functionalities were synthesized by cross-metathesis (CM) reaction of terminally olefinic esters with different acrylamides, catalyzed by Hoveyda-Grubbs 2nd generation catalyst. Chelation by amides of the catalyst ruthenium center caused low conversions using conventional solvents. The effects of both solvent and structure of acrylamide on reaction conversion were investigated. While the inherent tendency of acrylamides to chelate Ru is governed by the acrylamide N-substituents, employing acetic acid as a solvent significantly improved the conversion of certain acrylamides, from 50% to up to 99%. Homogeneous hydrogenation using p-toluenesulfonyl hydrazide successfully eliminated the α,β-unsaturation of the CM products to give stable amide-functionalized cellulose esters. The amide-functionalized product showed higher Tg than its starting terminally olefinic counterpart, which may have resulted from strong hydrogen bonding interactions of the amide functional groups.

  9. Synthesis of amide-functionalized cellulose esters by olefin cross-metathesis.

    PubMed

    Meng, Xiangtao; Edgar, Kevin J

    2015-11-01

    Cellulose esters with amide functionalities were synthesized by cross-metathesis (CM) reaction of terminally olefinic esters with different acrylamides, catalyzed by Hoveyda-Grubbs 2nd generation catalyst. Chelation by amides of the catalyst ruthenium center caused low conversions using conventional solvents. The effects of both solvent and structure of acrylamide on reaction conversion were investigated. While the inherent tendency of acrylamides to chelate Ru is governed by the acrylamide N-substituents, employing acetic acid as a solvent significantly improved the conversion of certain acrylamides, from 50% to up to 99%. Homogeneous hydrogenation using p-toluenesulfonyl hydrazide successfully eliminated the α,β-unsaturation of the CM products to give stable amide-functionalized cellulose esters. The amide-functionalized product showed higher Tg than its starting terminally olefinic counterpart, which may have resulted from strong hydrogen bonding interactions of the amide functional groups. PMID:26256383

  10. Fate of N-nitrosodimethylamine, trihalomethane and haloacetic acid precursors in tertiary treatment including biofiltration.

    PubMed

    Farré, Maria José; Reungoat, Julien; Argaud, Francois Xavier; Rattier, Maxime; Keller, Jürg; Gernjak, Wolfgang

    2011-11-01

    The presence of disinfection by-products (DBPs) such as trihalomethanes (THMs), haloacetic acids (HAAs) and N-nitrosamines in water is of great concern due to their adverse effects on human health. In this work, the removal of N-nitrosodimethylamine (NDMA), total THM and five HAA precursors from secondary effluent by biological activated carbon (BAC) is investigated at full and pilot scale. In the pilot plant two filter media, sand and granular activated carbon, are tested. In addition, we evaluate the influence of ozonation prior to BAC filtration on its performance. Among the bulk of NDMA precursors, the fate of four pharmaceuticals containing a dimethylamino moiety in the chemical structure are individually investigated. Both NDMA formation potential and each of the studied pharmaceuticals are dramatically reduced by the BAC even in the absence of main ozonation prior to the filtration. The low removal of NDMA precursors at the sand filtration in comparison to the removal of NDMA precursors at the BAC suggests that adsorption may play an important role on the removal of NDMA precursors by BAC. Contrary, the precursors for THM and HAA formation are reduced in both sand filtration and BAC indicating that the precursors for the formation of these DBPs are to some extent biodegradable.

  11. Differential regulation of host genes including hepatic fatty acid synthase in HBV-transgenic mice.

    PubMed

    Zhang, Hongmin; Li, Hong; Yang, Yixuan; Li, Sanglin; Ren, Hong; Zhang, Dazhi; Hu, Huaidong

    2013-06-01

    Hepatitis B virus (HBV) is the most common of the hepatitis viruses that cause chronic liver infections in humans, and it is considered to be a major global health problem. To gain a better understanding of HBV pathogenesis, and identify novel putative targets for anti-HBV therapy, this study was designed to elucidate the differential expression of host proteins in liver tissue from HBV-transgenic mice. Liver samples from two groups, (1) HBV-transgenic (Tg) mice, (2) corresponding background normal mice, wild-type (WT) mice, were collected and subjected to iTRAQ and mass spectrometry analysis. In total, 1950 unique proteins were identified, and 68 proteins were found to be differentially expressed in HBV-Tg mice as compared with that in WT mice. Several differentially expressed proteins were further validated by real-time quantitative RT-PCR, Western blot and immunohistochemical analysis. Furthermore, the association of HBV replication with fatty acid synthase (FASN), one of the highly expressed proteins in HBV-Tg mice, was verified. Silencing of FASN expression in HepG2.2.15 cells suppressed viral replication through the IFN signaling pathway, and some downstream antiviral effectors. The implicated role of FASN in HBV replication provides an opportunity to test existing compounds against FASN for adjuvant therapy and/or treatment of HBV replication. PMID:23675653

  12. Chemical Genetics Uncovers Novel Inhibitors of Lignification, Including p-Iodobenzoic Acid Targeting CINNAMATE-4-HYDROXYLASE.

    PubMed

    Van de Wouwer, Dorien; Vanholme, Ruben; Decou, Raphaël; Goeminne, Geert; Audenaert, Dominique; Nguyen, Long; Höfer, René; Pesquet, Edouard; Vanholme, Bartel; Boerjan, Wout

    2016-09-01

    Plant secondary-thickened cell walls are characterized by the presence of lignin, a recalcitrant and hydrophobic polymer that provides mechanical strength and ensures long-distance water transport. Exactly the recalcitrance and hydrophobicity of lignin put a burden on the industrial processing efficiency of lignocellulosic biomass. Both forward and reverse genetic strategies have been used intensively to unravel the molecular mechanism of lignin deposition. As an alternative strategy, we introduce here a forward chemical genetic approach to find candidate inhibitors of lignification. A high-throughput assay to assess lignification in Arabidopsis (Arabidopsis thaliana) seedlings was developed and used to screen a 10-k library of structurally diverse, synthetic molecules. Of the 73 compounds that reduced lignin deposition, 39 that had a major impact were retained and classified into five clusters based on the shift they induced in the phenolic profile of Arabidopsis seedlings. One representative compound of each cluster was selected for further lignin-specific assays, leading to the identification of an aromatic compound that is processed in the plant into two fragments, both having inhibitory activity against lignification. One fragment, p-iodobenzoic acid, was further characterized as a new inhibitor of CINNAMATE 4-HYDROXYLASE, a key enzyme of the phenylpropanoid pathway synthesizing the building blocks of the lignin polymer. As such, we provide proof of concept of this chemical biology approach to screen for inhibitors of lignification and present a broad array of putative inhibitors of lignin deposition for further characterization. PMID:27485881

  13. Direct Reaction of Amides with Nitric Oxide To Form Diazeniumdiolates

    PubMed Central

    2015-01-01

    We report the apparently unprecedented direct reaction of nitric oxide (NO) with amides to generate ions of structure R(C=O)NH–N(O)=NO–, with examples including R = Me (1a) or 3-pyridyl (1b). The sodium salts of both released NO in pH 7.4 buffer, with 37 °C half-lives of 1–3 min. As NO-releasing drug candidates, diazeniumdiolated amides would have the advantage of generating only 1 equiv of base on hydrolyzing exhaustively to NO, in contrast to their amine counterparts, which generate 2 equiv of base. PMID:25210948

  14. Longitudinal distributions of dicarboxylic acids, ω-oxoacids, pyruvic acid, α-dicarbonyls, and fatty acids in the marine aerosols from the central Pacific including equatorial upwelling

    NASA Astrophysics Data System (ADS)

    Hoque, Mir Md. Mozammal; Kawamura, Kimitaka

    2016-03-01

    Remote marine aerosol samples (total suspended particles) were collected during a cruise in the central Pacific from Japan to Mexico (1°59'N-35°N and 171°54'E-90°58'W). The aerosol samples were analyzed for dicarboxylic acids (C2-C11), ω-oxoacids, pyruvic acid, α-dicarbonyls, and fatty acids as well as organic and elemental carbon, water-soluble organic carbon, and total nitrogen (WSTN). During the study, diacids were the most abundant compound class followed by fatty acids, ω-oxoacids, and α-dicarbonyls. Molecular compositions of diacids showed a predominance of oxalic (C2) acid followed by malonic (C3) and succinic (C4) acids. Oxalic acid comprises 74% of total diacids. This result suggests that photochemical production of oxalic acid is significant over the central Pacific. Spatial distributions of diacids, ω-oxoacids, pyruvic acid, α-dicarbonyls, and fatty acids together with total carbon and WSTN showed higher abundances in the eastern equatorial Pacific where the upwelling of high-nutrient waters followed by high biological productivity is common, indicating that their in situ production is important in the warmer central Pacific through photochemical oxidation from their gaseous and particulate precursors. This study demonstrates that there is a strong linkage in biogeochemical cycles of carbon in the sea-air interface via ocean upwelling, phytoplankton productivity, sea-to-air emissions of organic matter, and formation of secondary organic aerosols in the eastern equatorial Pacific.

  15. Sterically-controlled intermolecular Friedel-Crafts acylation with twisted amides via selective N-C cleavage under mild conditions.

    PubMed

    Liu, Yongmei; Meng, Guangrong; Liu, Ruzhang; Szostak, Michal

    2016-05-21

    Highly chemoselective Friedel-Crafts acylation with twisted amides under mild conditions is reported for the first time. The reaction shows high functional group tolerance, obviating the need for preformed sensitive organometallic reagents and expensive transition metal catalysts. The high reactivity of amides is switched on by ground-state steric distortion to disrupt the amide bond nN→πCO* resonance as a critical design feature. Conceptually, this new acid-promoted mechanism of twisted amides provides direct access to bench-stable acylating reagents under mild, metal-free conditions. PMID:27139813

  16. Condensation Reactions and Formation of Amides, Esters, and Nitriles Under Hydrothermal Conditions

    NASA Astrophysics Data System (ADS)

    Rushdi, Ahmed I.; Simoneit, Bernd R. T.

    2004-06-01

    Hydrothermal pyrolysis experiments were performed to assess condensation (dehydration) reactions to amide, ester, and nitrile functionalities from lipid precursors. Beside product formation, organic compound alteration and stability were also evaluated. Mixtures of nonadecanoic acid, hexadecanedioic acid, or hexadecanamide with water, ammonium bicarbonate, and oxalic acid were heated at 300°C for 72 h. In addition, mixtures of ammonium bicarbonate and oxalic acid solutions were used to test the abiotic formation of organic nitrogen compounds at the same temperature. The resulting products were condensation compounds such as amides, nitriles, and minor quantities of N-methylalkyl amides, alkanols, and esters. Mixtures of alkyl amide in water or oxalic acid yielded mainly hydrolysis and dehydration products, and with ammonium bicarbonate and oxalic acid the yield of condensation products was enhanced. The synthesis experiments with oxalic acid and ammonium bicarbonate solutions yielded homologous series of alkyl amides, alkyl amines, alkanes, and alkanoic acids, all with no carbon number predominances. These organic nitrogen compounds are stable and survive under the elevated temperatures of hydrothermal fluids.

  17. Characterization of the Amicetin Biosynthesis Gene Cluster from Streptomyces vinaceusdrappus NRRL 2363 Implicates Two Alternative Strategies for Amide Bond Formation

    PubMed Central

    Zhang, Gaiyun; Zhang, Haibo; Li, Sumei; Xiao, Ji; Zhang, Guangtao; Zhu, Yiguang; Niu, Siwen; Ju, Jianhua

    2012-01-01

    Amicetin, an antibacterial and antiviral agent, belongs to a group of disaccharide nucleoside antibiotics featuring an α-(1→4)-glycoside bond in the disaccharide moiety. In this study, the amicetin biosynthesis gene cluster was cloned from Streptomyces vinaceusdrappus NRRL 2363 and localized on a 37-kb contiguous DNA region. Heterologous expression of the amicetin biosynthesis gene cluster in Streptomyces lividans TK64 resulted in the production of amicetin and its analogues, thereby confirming the identity of the ami gene cluster. In silico sequence analysis revealed that 21 genes were putatively involved in amicetin biosynthesis, including 3 for regulation and transportation, 10 for disaccharide biosynthesis, and 8 for the formation of the amicetin skeleton by the linkage of cytosine, p-aminobenzoic acid (PABA), and the terminal (+)-α-methylserine moieties. The inactivation of the benzoate coenzyme A (benzoate-CoA) ligase gene amiL and the N-acetyltransferase gene amiF led to two mutants that accumulated the same two compounds, cytosamine and 4-acetamido-3-hydroxybenzoic acid. These data indicated that AmiF functioned as an amide synthethase to link cytosine and PABA. The inactivation of amiR, encoding an acyl-CoA-acyl carrier protein transacylase, resulted in the production of plicacetin and norplicacetin, indicating AmiR to be responsible for attachment of the terminal methylserine moiety to form another amide bond. These findings implicated two alternative strategies for amide bond formation in amicetin biosynthesis. PMID:22267658

  18. Characterization of the amicetin biosynthesis gene cluster from Streptomyces vinaceusdrappus NRRL 2363 implicates two alternative strategies for amide bond formation.

    PubMed

    Zhang, Gaiyun; Zhang, Haibo; Li, Sumei; Xiao, Ji; Zhang, Guangtao; Zhu, Yiguang; Niu, Siwen; Ju, Jianhua; Zhang, Changsheng

    2012-04-01

    Amicetin, an antibacterial and antiviral agent, belongs to a group of disaccharide nucleoside antibiotics featuring an α-(1→4)-glycoside bond in the disaccharide moiety. In this study, the amicetin biosynthesis gene cluster was cloned from Streptomyces vinaceusdrappus NRRL 2363 and localized on a 37-kb contiguous DNA region. Heterologous expression of the amicetin biosynthesis gene cluster in Streptomyces lividans TK64 resulted in the production of amicetin and its analogues, thereby confirming the identity of the ami gene cluster. In silico sequence analysis revealed that 21 genes were putatively involved in amicetin biosynthesis, including 3 for regulation and transportation, 10 for disaccharide biosynthesis, and 8 for the formation of the amicetin skeleton by the linkage of cytosine, p-aminobenzoic acid (PABA), and the terminal (+)-α-methylserine moieties. The inactivation of the benzoate coenzyme A (benzoate-CoA) ligase gene amiL and the N-acetyltransferase gene amiF led to two mutants that accumulated the same two compounds, cytosamine and 4-acetamido-3-hydroxybenzoic acid. These data indicated that AmiF functioned as an amide synthethase to link cytosine and PABA. The inactivation of amiR, encoding an acyl-CoA-acyl carrier protein transacylase, resulted in the production of plicacetin and norplicacetin, indicating AmiR to be responsible for attachment of the terminal methylserine moiety to form another amide bond. These findings implicated two alternative strategies for amide bond formation in amicetin biosynthesis.

  19. Bifunctional Brønsted Base Catalyzes Direct Asymmetric Aldol Reaction of α-Keto Amides.

    PubMed

    Echave, Haizea; López, Rosa; Palomo, Claudio

    2016-03-01

    The first enantioselective direct cross-aldol reaction of α-keto amides with aldehydes, mediated by a bifunctional ureidopeptide-based Brønsted base catalyst, is described. The appropriate combination of a tertiary amine base and an aminal, and urea hydrogen-bond donor groups in the catalyst structure promoted the exclusive generation of the α-keto amide enolate which reacted with either non-enolizable or enolizable aldehydes to produce highly enantioenriched polyoxygenated aldol adducts without side-products resulting from dehydration, α-keto amide self-condensation, aldehyde enolization, and isotetronic acid formation.

  20. Bifunctional Brønsted Base Catalyzes Direct Asymmetric Aldol Reaction of α-Keto Amides.

    PubMed

    Echave, Haizea; López, Rosa; Palomo, Claudio

    2016-03-01

    The first enantioselective direct cross-aldol reaction of α-keto amides with aldehydes, mediated by a bifunctional ureidopeptide-based Brønsted base catalyst, is described. The appropriate combination of a tertiary amine base and an aminal, and urea hydrogen-bond donor groups in the catalyst structure promoted the exclusive generation of the α-keto amide enolate which reacted with either non-enolizable or enolizable aldehydes to produce highly enantioenriched polyoxygenated aldol adducts without side-products resulting from dehydration, α-keto amide self-condensation, aldehyde enolization, and isotetronic acid formation. PMID:26835655

  1. Universal mechanism for breaking amide bonds by ionizing radiation

    NASA Astrophysics Data System (ADS)

    Johnson, Phillip S.; Cook, Peter L.; Liu, Xiaosong; Yang, Wanli; Bai, Yiqun; Abbott, Nicholas L.; Himpsel, F. J.

    2011-07-01

    The photodissociation of the amide bond by UV light and soft x-rays is investigated by x-ray absorption spectroscopy at the C, N, and O 1s edges. Irradiation leaves a clear and universal signature for a wide variety of amides, ranging from oligopeptides to large proteins and synthetic polyamides, such as nylon. As the π* peak of the amide bond shrinks, two new π* peaks appear at the N 1s edge with a characteristic splitting of 1.1 eV. An additional characteristic is the overall intensity reduction of both the π* and σ* features at the O 1s edge, which indicates loss of oxygen. The spectroscopic results are consistent with the release of the O atom from the amide bond, followed by the migration of the H atom from the N to one of its two C neighbors. Migration to the carbonyl C leads to an imine, and migration to the Cα of the amino acid residue leads to a nitrile. Imine and nitrile produce the two characteristic π* transitions at the N 1s edge. A variety of other models is considered and tested against the N 1s spectra of reference compounds.

  2. Amidation of esters with amino alcohols using organobase catalysis.

    PubMed

    Caldwell, Nicola; Campbell, Peter S; Jamieson, Craig; Potjewyd, Frances; Simpson, Iain; Watson, Allan J B

    2014-10-01

    A catalytic protocol for the base-mediated amidation of unactivated esters with amino alcohol derivatives is reported. Investigations into mechanistic aspects of the process indicate that the reaction involves an initial transesterification, followed by an intramolecular rearrangement. The reaction is highly general in nature and can be extended to include the synthesis of oxazolidinone systems through use of dimethyl carbonate. PMID:25226088

  3. Activation of amide N-H bonds by organotransition metal complexes

    SciTech Connect

    Schaad, D.R.

    1992-01-01

    This research was aimed at developing new homogeneous transition metal hydroamination catalysts, specifically for hydroamination reactions involving the addition of amides to olefins. New iron-, ruthenium-, palladium- and platinum-amido complexes were formed via amide N-H bond activation reactions to zerovalent and divalent organotransition metal complexes. Complexes of the general formula trans-MW(amido) (diphosphine)[sub 2] were synthesized by reaction of amides with FeH(C[sub 6]H[sub 4]PPhCH[sub 2]CH[sub 2]PPh[sub 2]) (dppe) and cis-RuHNp(dmpe)[sub 2]. Photolysis of cis-FeH[sub 2](dmpe)[sub 2] or Pt(C[sub 2]O[sub 4] (PEt[sub 3])[sub 2] in the presence of amides yielded trans-FeH(amido)(dmple)[sub 2] and trans-PtH (amido) IPEt[sub 3]) products. Reactions of amides with cis-M(PEtt[sub 3])[sub 2]Me[sub 2] yielded compounds with the general formula M(amido)Me(PEt[sub 3])[sub 2] (M = Pd, Pt). The reaction of M(diphosphine)Me[sub 2] complexes with amides produced compounds with the general formula M(amido)Me(diphosphine) (M = Pd, Pt). Reaction of amides with PtMe[sub 2](COD) yielded complexes with the general formula PtMe(amido)(COD). The compounds were characterized by multinuclear NMR spectroscopy. The reactions were proposed to occur by two routes: oxidative addition of the amid eN-H bond to the metal complex or direct protonation of the metal complex by the N-H bond of the amide. The rate of formation and the stability of the metal-amido products depended on the nature of the metal complex and the amide employed. Only acidic amides reacted with the iron complexes. For the thermal reactions of amides with the metal complexes, the reactions proceeded to completion faster as the acidity of the amide was increased. The new iron-, ruthenium-, palladium- and platinum-amido complexes were inert to further reaction.

  4. RNA-Binding Affinities and Crystal Structure of Oligonucleotides Containing Five-Atom Amide-Based Backbone Structures

    SciTech Connect

    Pallan, Pradeep S.; von Matt, Peter; Wilds, Christopher J.; Altmann, Karl-Heinz; Egli, Martin

    2010-03-08

    Among the hundreds of nucleic acid analogues that have been studied over the last two decades only very few exhibit backbones with linkers between residues that are either shorter or longer than the four-atom linker O3{prime}-P-O5{prime}-C5{prime} connecting sugar ring moieties in DNA and RNA. 2{prime}-Deoxyribonucleoside dimers connected by a five-atom linker O3{prime}-CH*(CH{sub 3})-CO-NH-CH{sub 2} (* designates a chiral center) were reported to lead to only a slight destabilization of RNA-DNA hybrids in which the DNA strand contained one or several of these amide-linked dimers (De Napoli, L., Iadonisi, A., Montesarchio, D., Varra, M., and Piccialli, G. (1995) Synthesis of thymidine dimers containing a new internucleosidic amide linkage and their incorporation into oligodeoxyribonucleotides, Bioorg. Med. Chem. Lett. 5, 1647-1652). To analyze the influence of various chemistries of such five-atom amide linkers on the RNA-binding affinity of modified DNA strands, we have synthesized five different amide-linked dimers, including structures with homochiral linkers of the type X3{prime}-C*H(CH{sub 3})-CO-NH-CH{sub 2} (X = O, CH{sub 2}) as well as the corresponding analogues carrying methoxy groups at the 2{prime}-position of the 3{prime}-nucleosides. We have conducted a detailed thermodynamic analysis of duplex formation between the modified DNA and RNA, with the DNA strands containing between one and seven consecutive modified dimers. Some of the five-atom-linked dimers lead to significantly higher RNA-binding affinities compared with that of native DNA. Interestingly, the linkers with opposite stereochemistry at the chiral center stabilize duplexes between the modified DNA and RNA to different degrees. CD spectroscopy in solution and a crystal structure of an RNA-DNA duplex with a single amide-linked dimer demonstrate that the longer amide backbones do not disrupt the duplex geometry. These observations provide further evidence that stable cross-pairing between two

  5. The synthesis of sterically hindered amides.

    PubMed

    Schäfer, Gabriel; Bode, Jeffrey W

    2014-01-01

    Amide bond formation is one of the most important reactions due to the ubiquity of the amide functional group in pharmaceuticals and biologically active compounds. However, even the best existing methods reach their limits when it comes to the synthesis of sterically hindered amides. In this article we summarize our research in the formation of sterically hindered amides. We show that the direct coupling of Grignard reagents to isocyanates provides a facile and robust solution to this long-standing challenge and hope that this methodology will find widespread application in the synthesis of pharmaceuticals and materials. PMID:24983609

  6. Actinide-lanthanide separation with solvents on the base of amides of heterocyclic diacids

    SciTech Connect

    Babain, V.A.; Alyapyshev, M.Y.; Tkachenko, L.I.

    2013-07-01

    The separation of actinides from lanthanides with a particular emphasis on Am(III) from Eu(III) with amides of heterocyclic dicarboxylic diacids was reviewed. It was shown that the di-amides of the 2,2'-dipyridyl-6,6'-dicarboxylic acid are the most promising ligands for the simultaneous selective recovery of actinides from HLLW (high level radioactive liquid waste) within the GANEX concept. (author)

  7. Poly(amide-graft-acrylate) interfacial compounds

    NASA Astrophysics Data System (ADS)

    Zamora, Michael Perez

    Graft copolymers with segments of dissimilar chemistries have been shown to be useful in a variety of applications as surfactants, compatibilizers, impact modifiers, and surface modifiers. The most common route to well defined graft copolymers is through the use of macromonomers, polymers containing a reactive functionality and thus capable of further polymerization. However, the majority of the studies thus far have focused on the synthesis of macromonomers capable of reacting with vinyl monomers to form graft copolymers. This study focused on the synthesis of macromonomers capable of participating in condensation polymerizations. A chain transfer functionalization method was utilized. Cysteine was evaluated as a chain transfer agent for the synthesis of amino acid functionalized poly(acrylate) and poly(methacrylate) macromonomers. Low molar mass, functionalized macromonomers were produced. These macromonomers were proven to be capable of reacting with amide precursors to form poly(amide-g-acrylate) graft copolymers. Macromonomers and graft copolymers were characterized by gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) spectroscopy, elemental analysis (EA), inductively coupled plasma (ICP), and differential scanning calorimetry (DSC). The second part of this research involved poly(dimethacrylate) dental restorative materials. Volumetric shrinkage during the cure of these resins results in a poor interface between the resin and the remaining tooth structure, limiting the lifetime of these materials. Cyclic anhydrides were incorporated into common monomer compositions used in dental applications. Volume expansion from the ring opening hydrolysis of these anhydrides was shown to be feasible. The modified dental resins were characterized by swelling, extraction and ultraviolet spectroscopy (UV), and density measurements. Linear poLymers designed to model the crosslinked dental resins were

  8. Structure-based Mechanistic Insights into Terminal Amide Synthase in Nosiheptide-Represented Thiopeptides Biosynthesis

    PubMed Central

    Liu, Shanshan; Guo, Heng; Zhang, Tianlong; Han, Li; Yao, Pengfei; Zhang, Yan; Rong, Naiyan; Yu, Yi; Lan, Wenxian; Wang, Chunxi; Ding, Jianping; Wang, Renxiao; Liu, Wen; Cao, Chunyang

    2015-01-01

    Nosiheptide is a parent compound of thiopeptide family that exhibit potent activities against various bacterial pathogens. Its C-terminal amide formation is catalyzed by NosA, which is an unusual strategy for maturating certain thiopeptides by processing their precursor peptides featuring a serine extension. We here report the crystal structure of truncated NosA1-111 variant, revealing three key elements, including basic lysine 49 (K49), acidic glutamic acid 101 (E101) and flexible C-terminal loop NosA112-151, are crucial to the catalytic terminal amide formation in nosiheptide biosynthesis. The side-chain of residue K49 and the C-terminal loop fasten the substrate through hydrogen bonds and hydrophobic interactions. The side-chain of residue E101 enhances nucleophilic attack of H2O to the methyl imine intermediate, leading to Cα-N bond cleavage and nosiheptide maturation. The sequence alignment of NosA and its homologs NocA, PbtH, TpdK and BerI, and the enzymatic assay suggest that the mechanistic studies on NosA present an intriguing paradigm about how NosA family members function during thiopeptide biosynthesis. PMID:26244829

  9. Selected nutrient contents, fatty acid composition, including conjugated linoleic acid, and retention values in separable lean from lamb rib loins as affected by external fat and cooking method.

    PubMed

    Badiani, Anna; Montellato, Lara; Bochicchio, Davide; Anfossi, Paola; Zanardi, Emanuela; Maranesi, Magda

    2004-08-11

    Proximate composition and fatty acid profile, conjugated linoleic acid (CLA) isomers included, were determined in separable lean of raw and cooked lamb rib loins. The cooking methods compared, which were also investigated for cooking yields and true nutrient retention values, were dry heating of fat-on cuts and moist heating of fat-off cuts; the latter method was tested as a sort of dietetic approach against the more traditional former type. With significantly (P < 0.05) lower cooking losses, dry heating of fat-on rib-loins produced slightly (although only rarely significantly) higher retention values for all of the nutrients considered, including CLA isomers. On the basis of the retention values obtained, both techniques led to a minimum migration of lipids into the separable lean, which was higher (P < 0.05) in dry heating than in moist heating, and was characterized by the prevalence of saturated and monounsaturated fatty acids. On the whole, the response to cooking of the class of CLA isomers (including that of the nutritionally most important isomer cis-9,trans-11) was more similar to that of the monounsaturated than the polyunsaturated fatty acids.

  10. An orally active cathepsin K inhibitor, furan-2-carboxylic acid, 1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide (OST-4077), inhibits osteoclast activity in vitro and bone loss in ovariectomized rats.

    PubMed

    Kim, M K; Kim, H D; Park, J H; Lim, J I; Yang, J S; Kwak, W Y; Sung, S Y; Kim, H J; Kim, S H; Lee, C H; Shim, J Y; Bae, M H; Shin, Y A; Huh, Y; Han, T D; Chong, W; Choi, H; Ahn, B N; Yang, S O; Son, M H

    2006-08-01

    Human cathepsin K, a cysteine proteinase of the papain family, has been recognized as a potential drug target for the treatment of osteoporosis. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel antiresorptive drugs. Now, we report the pharmacological properties of OST-4077 [furan-2-carboxylic acid (1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide] as a novel selective cathepsin K inhibitor. Human and rat cathepsin K were inhibited in vitro by OST-4077 with the IC50 values of 11 and 427 nM, respectively. OST-4077 suppressed bone resorption induced by rabbit osteoclasts (IC50, 37 nM) but did not affect bone mineralization or cellular alkaline phosphatase activity in MC3T3-E1 cells. Parathyroid hormone-induced bone resorption was inhibited in a dose-dependent manner in thyroparathyroidectomized rats gavaged with a single dose of OST-4077 (ED50, 69 mg/kg). When given orally twice daily for 4 weeks to 3-month-old ovariectomized (OVX) rats, OST-4077 dose-dependently prevented bone loss, as monitored by bone densitometry, ash content, and urinary excretion of deoxypyridinoline. No change in serum osteocalcin in the OVX rats by OST-4077 suggested that bone formation might not be affected by the agent. In summary, OST-4077 selectively inhibited bone resorbing activities of osteoclasts and prevented bone loss induced by estrogen deficiency but did not affect bone formation. OST-4077, an orally active selective human cathepsin K inhibitor, may have the therapeutic potential for the treatment of diseases characterized by excessive bone loss including osteoporosis.

  11. Yttrium (amidate) complexes for catalytic C-N bond formation. Rapid, room temperature amidation of aldehydes.

    PubMed

    Thomson, Jaclyn A; Schafer, Laurel L

    2012-07-14

    Yttrium (amidate) precatalysts are highly active for the mild amidation of aldehydes with amines. Reactions occur at room temperature within 5 min in up to 98% isolated yield. These rare-earth systems are effective for this transformation in the absence of supplementary heat, light, base, or oxidants. The reaction proceeds with functionalized amines and/or aldehydes. A comparison of various amidate precatalysts in combination with reaction monitoring suggests that the targeted amide products formed during the reaction promote the formation of alternative catalytically active amidate species in situ.

  12. Isotope-enriched protein standards for computational amide I spectroscopy

    SciTech Connect

    Reppert, Mike; Roy, Anish R.; Tokmakoff, Andrei

    2015-03-28

    We present a systematic isotope labeling study of the protein G mutant NuG2b as a step toward the production of reliable, structurally stable, experimental standards for amide I infrared spectroscopic simulations. By introducing isotope enriched amino acids into a minimal growth medium during bacterial expression, we induce uniform labeling of the amide bonds following specific amino acids, avoiding the need for chemical peptide synthesis. We use experimental data to test several common amide I frequency maps and explore the influence of various factors on map performance. Comparison of the predicted absorption frequencies for the four maps tested with empirical assignments to our experimental spectra yields a root-mean-square error of 6-12 cm{sup −1}, with outliers of at least 12 cm{sup −1} in all models. This means that the predictions may be useful for predicting general trends such as changes in hydrogen bonding configuration; however, for finer structural constraints or absolute frequency assignments, the models are unreliable. The results indicate the need for careful testing of existing literature maps and shed light on possible next steps for the development of quantitative spectral maps.

  13. Synthesis of Carfentanil Amide Opioids Using the Ugi Multicomponent Reaction

    PubMed Central

    Váradi, András; Palmer, Travis C.; Haselton, Nathan; Afonin, Daniel; Subrath, Joan J.; Le Rouzic, Valerie; Hunkele, Amanda; Pasternak, Gavril W.; Marrone, Gina F.; Borics, Attila; Majumdar, Susruta

    2015-01-01

    We report a novel approach to synthesize carfentanil amide analogues utilizing the isocyanide-based four-component Ugi multicomponent reaction. A small library of bis-amide analogues of carfentanil was created using N-alkylpiperidones, aniline, propionic acid, and various aliphatic isocyanides. Our lead compound showed high affinity for mu (MOR) and delta opioid receptors (DOR) with no appreciable affinity for kappa (KOR) receptors in radioligand binding assays. The compound was found to be a mixed MOR agonist/partial DOR agonist in [35S]GTPγS functional assays, and it showed moderate analgesic potency in vivo. The compound showed no visible signs of physical dependence or constipation in mice. In addition, it produced less respiratory depression than morphine. Most mixed MOR/DOR opioids reported in the literature are peptides and thereby systemically inactive. Our approach utilizing a multicomponent reaction has the promise to deliver potent and efficacious small-molecule analgesics with potential clinical utility. PMID:26148793

  14. Production of R-(-)-Ketoprofen from an Amide Compound by Comamonas acidovorans KPO-2771-4

    PubMed Central

    Yamamoto, K.; Otsubo, K.; Matsuo, A.; Hayashi, T.; Fujimatsu, I.; Komatsu, K.

    1996-01-01

    R-(-)-2-(3(prm1)-Benzoylphenyl)propionic acid [R-(-)-ketoprofen] was produced from racemic 2-(3(prm1)-benzoylphenyl)propionamide (keto-amide) by the isolated bacterial strain Comamonas acidovorans KPO-2771-4. Sodium fumarate as the carbon source and 2-azacyclononanone or isobutyronitrile as the enhancer in the culture medium were effective for bacterial growth and the enhancement of R-(-)-ketoprofen-producing activity. R-(-)-Ketoprofen produced from the keto-amide by resting cells was present in 99% enantiomeric exess. C. acidovorans KPO-2771-4 has an R-enantioselective amidase for keto-amide because the purified amidase from the bacterium hydrolyzed keto-amide, producing optically pure R-ketoprofen and ammonia. PMID:16535206

  15. A two-step approach to achieve secondary amide transamidation enabled by nickel catalysis

    PubMed Central

    Baker, Emma L.; Yamano, Michael M.; Zhou, Yujing; Anthony, Sarah M.; Garg, Neil K.

    2016-01-01

    A long-standing challenge in synthetic chemistry is the development of the transamidation reaction. This process, which involves the conversion of one amide to another, is typically plagued by unfavourable kinetic and thermodynamic factors. Although some advances have been made with regard to the transamidation of primary amide substrates, secondary amide transamidation has remained elusive. Here we present a simple two-step approach that allows for the elusive overall transformation to take place using non-precious metal catalysis. The methodology proceeds under exceptionally mild reaction conditions and is tolerant of amino-acid-derived nucleophiles. In addition to overcoming the classic problem of secondary amide transamidation, our studies expand the growing repertoire of new transformations mediated by base metal catalysis. PMID:27199089

  16. Synthesis and structure assignments of amide protected nucleosides and their use as phosphoramidites in deoxyoligonucleotide synthesis.

    PubMed Central

    Mag, M; Engels, J W

    1988-01-01

    The syntheses of several amide protected deoxyguanosine- as well as thymidine nucleosides are described. These compounds were synthesized according to the Mitsunobu reaction and Michael addition. In contradiction to previous studies we have discovered that the Michael addition gives only products derived from N-alkylation. The occurrence of N- or O-alkylation was assigned by means of two dimensional 1H, 1 3 C-COLOC-NMR spectroscopy. Further, we have found that the Mitsunobu reaction used for the protection of the amide function of dG is limited to alcohols without acidic hydrogen atoms. Amide protected phosphormidites (15, 16) were used for the preparation of deoxyoligonucleotides with a large number of guanine and thymine bases using two different coupling times. We have shown that there is no experimentally detectable difference in the quality of the products if the starting monomer is amide protected or not. Images PMID:3375062

  17. Synthesis and structure assignments of amide protected nucleosides and their use as phosphoramidites in deoxyoligonucleotide synthesis.

    PubMed

    Mag, M; Engels, J W

    1988-04-25

    The syntheses of several amide protected deoxyguanosine- as well as thymidine nucleosides are described. These compounds were synthesized according to the Mitsunobu reaction and Michael addition. In contradiction to previous studies we have discovered that the Michael addition gives only products derived from N-alkylation. The occurrence of N- or O-alkylation was assigned by means of two dimensional 1H, 1 3 C-COLOC-NMR spectroscopy. Further, we have found that the Mitsunobu reaction used for the protection of the amide function of dG is limited to alcohols without acidic hydrogen atoms. Amide protected phosphormidites (15, 16) were used for the preparation of deoxyoligonucleotides with a large number of guanine and thymine bases using two different coupling times. We have shown that there is no experimentally detectable difference in the quality of the products if the starting monomer is amide protected or not. PMID:3375062

  18. Temporal changes (1997-2012) of perfluoroalkyl acids and selected precursors (including isomers) in Swedish human serum.

    PubMed

    Gebbink, Wouter A; Glynn, Anders; Berger, Urs

    2015-04-01

    Concentrations (including isomer patterns) and temporal changes (1997-2012) of perfluoroalkyl acids (PFAAs) and selected perfluorooctane sulfonate (PFOS) and perfluoroalkyl carboxylic acid (PFCA) precursors were determined in serum samples from Swedish women. Perfluorooctane sulfonamide (FOSA) and perfluorooctane sulfonamidoacetic acid (FOSAA), as well as its N-methyl and N-ethyl derivatives (MeFOSAA and EtFOSAA) were consistently detected. Highest PFOS precursor concentrations were found for EtFOSAA (before year 2000) or MeFOSAA and FOSAA (after 2000). Disappearance half-lives for all PFOS precursors were shorter compared to PFOS. 4:2/6:2 and 6:2/6:2 polyfluoroalkyl phosphate diesters (diPAPs) were detected in <60% of the samples, whereas 6:2/8:2 and 8:2/8:2 diPAPs were detected in >60% of the samples, but showed no significant change in concentrations over time. Linear and sum-branched isomers were quantified separately for three PFAAs and three precursors. Significant changes between 1997 and 2012 in the % linear isomer were observed for PFOA and FOSA (increase) and PFOS (decrease).

  19. Determination of Structures and Energetics of Small- and Medium-Sized One-Carbon-Bridged Twisted Amides using ab Initio Molecular Orbital Methods: Implications for Amidic Resonance along the C-N Rotational Pathway.

    PubMed

    Szostak, Roman; Aubé, Jeffrey; Szostak, Michal

    2015-08-21

    Twisted amides containing nitrogen at the bridgehead position are attractive practical prototypes for the investigation of the electronic and structural properties of nonplanar amide linkages. Changes that occur during rotation around the N-C(O) axis in one-carbon-bridged twisted amides have been studied using ab initio molecular orbital methods. Calculations at the MP2/6-311++G(d,p) level performed on a set of one-carbon-bridged lactams, including 20 distinct scaffolds ranging from [2.2.1] to [6.3.1] ring systems, with the C═O bond on the shortest bridge indicate significant variations in structures, resonance energies, proton affinities, core ionization energies, frontier molecular orbitals, atomic charges, and infrared frequencies that reflect structural changes corresponding to the extent of resonance stabilization during rotation along the N-C(O) axis. The results are discussed in the context of resonance theory and activation of amides toward N-protonation (N-activation) by distortion. This study demonstrates that one-carbon-bridged lactams-a class of readily available, hydrolytically robust twisted amides-are ideally suited to span the whole spectrum of the amide bond distortion energy surface. Notably, this study provides a blueprint for the rational design and application of nonplanar amides in organic synthesis. The presented findings strongly support the classical amide bond resonance model in predicting the properties of nonplanar amides.

  20. Amide bond cleavage initiated by coordination with transition metal ions and tuned by an auxiliary ligand.

    PubMed

    Yang, Yongpo; Lu, Chunxin; Wang, Hailong; Liu, Xiaoming

    2016-06-21

    The reaction of ligand , N,N-bis(pyridin-2-ylmethyl)acetamide, with five transition metal salts, FeCl3·6H2O, CuCl2·2H2O, Cu(ClO4)2·6H2O, ZnCl2 and K2PtCl4/KI, produced five metal complexes, [(μ-O)(FeClL')(FeCl3)] (), [CuLCl2] (), [CuBPA(ClO4)(CHCN)] ClO4 (), [ZnLCl2] () and [PtLI2] (), where = 1-(2,4,5-tri(pyridin-2-yl)-3-(pyridin-2-ylmethyl)imidazolidin-1-yl)ethanone which formed in situ, and BPA = bis(pyridin-2-ylmethyl)amine. The ligand and complexes were characterized by a variety of spectroscopic techniques including X-ray single crystal diffraction where applicable. Depending on the metal ion and auxiliary ligand of the complex, the acetyl group of the ligand could be either intact or cleaved. When ferric chloride hexahydrate was used, the deacetylation proceeded even further and a novel heterocyclic compound () was formed in situ. A possible mechanism was proposed for the formation of the heterocyclic compound found in complex . Our results indicate that to cleave effectively an amide bond, it is essential for a metal centre to bind to the amide bond and the metal centre is of sufficient Lewis acidity.

  1. Dissecting Hofmeister Effects: Direct Anion-Amide Interactions Are Weaker than Cation-Amide Binding.

    PubMed

    Balos, Vasileios; Kim, Heejae; Bonn, Mischa; Hunger, Johannes

    2016-07-01

    Whereas there is increasing evidence for ion-induced protein destabilization through direct ion-protein interactions, the strength of the binding of anions to proteins relative to cation-protein binding has remained elusive. In this work, the rotational mobility of a model amide in aqueous solution was used as a reporter for the interactions of different anions with the amide group. Protein-stabilizing salts such as KCl and KNO3 do not affect the rotational mobility of the amide. Conversely, protein denaturants such as KSCN and KI markedly reduce the orientational freedom of the amide group. Thus these results provide evidence for a direct denaturation mechanism through ion-protein interactions. Comparing the present findings with results for cations shows that in contrast to common belief, anion-amide binding is weaker than cation-amide binding. PMID:27237055

  2. Influence of cold stress on contents of soluble sugars, vitamin C and free amino acids including gamma-aminobutyric acid (GABA) in spinach (Spinacia oleracea).

    PubMed

    Yoon, Young-Eun; Kuppusamy, Saranya; Cho, Kye Man; Kim, Pil Joo; Kwack, Yong-Bum; Lee, Yong Bok

    2017-01-15

    The contents of soluble sugars (sucrose, fructose, glucose, maltose and raffinose), vitamin C and free amino acids (34 compounds, essential and non-essential) were quantified in open-field and greenhouse-grown spinaches in response to cold stress using liquid chromatography. In general, greenhouse cultivation produced nutritionally high value spinach in a shorter growing period, where the soluble sugars, vitamin C and total amino acids concentrations, including essential were in larger amounts compared to those grown in open-field scenarios. Further, low temperature exposure of spinach during a shorter growth period resulted in the production of spinach with high sucrose, ascorbate, proline, gamma-aminobutyric acid, valine and leucine content, and these constitute the most important energy/nutrient sources. In conclusion, cultivation of spinach in greenhouse at a low temperature (4-7°C) and exposure for a shorter period (7-21days) before harvest is recommended. This strategy will produce a high quality product that people can eat. PMID:27542466

  3. Influence of cold stress on contents of soluble sugars, vitamin C and free amino acids including gamma-aminobutyric acid (GABA) in spinach (Spinacia oleracea).

    PubMed

    Yoon, Young-Eun; Kuppusamy, Saranya; Cho, Kye Man; Kim, Pil Joo; Kwack, Yong-Bum; Lee, Yong Bok

    2017-01-15

    The contents of soluble sugars (sucrose, fructose, glucose, maltose and raffinose), vitamin C and free amino acids (34 compounds, essential and non-essential) were quantified in open-field and greenhouse-grown spinaches in response to cold stress using liquid chromatography. In general, greenhouse cultivation produced nutritionally high value spinach in a shorter growing period, where the soluble sugars, vitamin C and total amino acids concentrations, including essential were in larger amounts compared to those grown in open-field scenarios. Further, low temperature exposure of spinach during a shorter growth period resulted in the production of spinach with high sucrose, ascorbate, proline, gamma-aminobutyric acid, valine and leucine content, and these constitute the most important energy/nutrient sources. In conclusion, cultivation of spinach in greenhouse at a low temperature (4-7°C) and exposure for a shorter period (7-21days) before harvest is recommended. This strategy will produce a high quality product that people can eat.

  4. Impact of hedonic evaluation on consumers' preferences for beef attributes including its enrichment with n-3 and CLA fatty acids.

    PubMed

    Baba, Yasmina; Kallas, Zein; Costa-Font, Montserrat; Gil, José María; Realini, Carolina E

    2016-01-01

    The impact of hedonic evaluation on consumers' preferences for beef attributes was evaluated (origin, animal diet, fat content, color, price) including its enrichment with omega-3 (n-3) and conjugated linoleic acid (CLA) fatty acids. One group of consumers (n=325) received information about n-3 and CLA, while the other group (n=322) received no information. Consumers conducted a Discrete Choice Experiment (DCE), using the recently developed Generalized Multinomial Logit model; followed by a blind hedonic evaluation of beef samples, which were identified after tasting, and finally repeated the DCE. Results showed that hedonic evaluation had a significant impact on consumers' preferences, which were similar after tasting for all consumers, with less emphasis on the fat content, color, and origin attributes and greater emphasis on animal diet. Preference for n-3 enriched beef increased, while preference for CLA enriched beef was still not significant after tasting. The information provided had a significant effect on consumers' beef preferences, but no significant impact on beef liking scores.

  5. Impact of hedonic evaluation on consumers' preferences for beef attributes including its enrichment with n-3 and CLA fatty acids.

    PubMed

    Baba, Yasmina; Kallas, Zein; Costa-Font, Montserrat; Gil, José María; Realini, Carolina E

    2016-01-01

    The impact of hedonic evaluation on consumers' preferences for beef attributes was evaluated (origin, animal diet, fat content, color, price) including its enrichment with omega-3 (n-3) and conjugated linoleic acid (CLA) fatty acids. One group of consumers (n=325) received information about n-3 and CLA, while the other group (n=322) received no information. Consumers conducted a Discrete Choice Experiment (DCE), using the recently developed Generalized Multinomial Logit model; followed by a blind hedonic evaluation of beef samples, which were identified after tasting, and finally repeated the DCE. Results showed that hedonic evaluation had a significant impact on consumers' preferences, which were similar after tasting for all consumers, with less emphasis on the fat content, color, and origin attributes and greater emphasis on animal diet. Preference for n-3 enriched beef increased, while preference for CLA enriched beef was still not significant after tasting. The information provided had a significant effect on consumers' beef preferences, but no significant impact on beef liking scores. PMID:26331961

  6. Synthesis and characterization of ester and amide derivatives of titanium(IV) carboxymethylphosphonate

    SciTech Connect

    Melánová, Klára; Beneš, Ludvík; Trchová, Miroslava; Svoboda, Jan; Zima, Vítězslav

    2013-06-15

    A set of layered ester and amide derivatives of titanium(IV) carboxymethylphosphonate was prepared by solvothermal treatment of amorphous titanium(IV) carboxymethylphosphonate with corresponding 1-alkanols, 1,ω-alkanediols, 1-aminoalkanes, 1,ω-diaminoalkanes and 1,ω-amino alcohols and characterized by powder X-ray diffraction, IR spectroscopy and thermogravimetric analysis. Whereas alkyl chains with one functional group form bilayers tilted to the layers, 1,ω-diaminoalkanes and most of 1,ω-alkanediols form bridges connecting the adjacent layers. In the case of amino alcohols, the alkyl chains form bilayer and either hydroxyl or amino group is used for bonding. This simple method for the synthesis of ester and amide derivatives does not require preparation of acid chloride derivative as a precursor or pre-intercalation with alkylamines and can be used also for the preparation of ester and amide derivatives of titanium carboxyethylphosphonate and zirconium carboxymethylphosphonate. - Graphical abstract: Ester and amide derivatives of layered titanium carboxymethylphosphonate were prepared by solvothermal treatment of amorphous solid with alkanol or alkylamine. - Highlights: • Ester and amide derivatives of titanium carboxymethylphosphonate. • Solvothermal treatment of amorphous solid with alkanol or alkylamine. • Ester and amide formation confirmed by IR spectroscopy.

  7. Oligonuclear ferrocene amides: mixed-valent peptides and potential redox-switchable foldamers.

    PubMed

    Siebler, Daniel; Linseis, Michael; Gasi, Teuta; Carrella, Luca M; Winter, Rainer F; Förster, Christoph; Heinze, Katja

    2011-04-11

    Trinuclear ferrocene tris-amides were synthesized from an Fmoc- or Boc-protected ferrocene amino acid, and hydrogen-bonded zigzag conformations were determined by NMR spectroscopy, molecular modelling, and X-ray diffraction. In these ordered secondary structures orientation of the individual amide dipole moments approximately in the same direction results in a macrodipole moment similar to that of α-helices composed of α-amino acids. Unlike ordinary α-amino acids, the building blocks in these ferrocene amides with defined secondary structure can be sequentially oxidized to mono-, di-, and trications. Singly and doubly charged mixed-valent cations were probed experimentally by Vis/NIR, paramagnetic ¹H NMR and Mössbauer spectroscopy and investigated theoretically by DFT calculations. According to the appearance of intervalence charge transfer (IVCT) bands in solution, the ferrocene/ferrocenium amides are described as Robin-Day class II mixed-valent systems. Mössbauer spectroscopy indicates trapped valences in the solid state. The secondary structure of trinuclear ferrocene tris-amides remains intact (coiled form) upon oxidation to mono- and dications according to DFT calculations, while oxidation to the trication should break the intramolecular hydrogen bonding and unfold the ferrocene peptide (uncoiled form).

  8. Carbazole and amide alkaloids from the stems of Clausena lansium.

    PubMed

    Du, Yi-Qian; Liu, Hang; Li, Chuang-Jun; Yang, Jing-Zhi; Ma, Jie; Zhang, Dan; Sun, Hua; Zhang, Dong-Ming

    2015-01-01

    Two new carbazole alkaloids, claulansine S (1) and claulansine T (2), and one new amide alkaloid, clauamide A (3), together with four known analogues (4-7) were isolated from the stems of Clausena lansium. Their structures were elucidated on the basis of spectroscopic analyses, including UV, IR, and NMR experiments (HSQC, HMBC, and NOE experiments). Compounds 4 and 6 showed moderate hepatoprotective activities. PMID:26095884

  9. Amide functionalized MWNT/SPEEK composite membrane for better electrochemical performance

    NASA Astrophysics Data System (ADS)

    Gahlot, Swati; Sharma, Prem P.; Kulshrestha, Vaibhav

    2016-05-01

    Nanocomposite membranes based on multiwalled carbon nanotube /SPEEK (sulfonated poly ether ether ketone) have been synthesized via simple solution casting. Prior to use CNT have been purified and grafted with carboxylic acid groups onto its walls by means of sulfuric and nitric acid. Afterwards, amidation of carboxylated CNTs (c-CNT) has been done. Amidated CNT (a-CNT) is then incorporated in SPEEK polymer matrix to synthesize nanocomposite membranes. Physicochemical, structural, thermal and mechanical characterizations are done through the respective techniques. Electric and ionic conductivities have also been evaluated. Composites membranes show the enhanced electrochemical performance with higher electric conductivity.

  10. Analysis of hydrogen bonds in peptides, based on the hydration affinity of amides

    NASA Astrophysics Data System (ADS)

    Perczel, András; Lengyel, Istvan; Mantsch, Henry H.; Fasman, Gerald D.

    1993-08-01

    The difference in the affinity for water of peptide groups embedded in different molecular environments was investigated. The chemical shift of an amide proton is sensitive to conformational variations, as well as to changes in the molecular environment [D.S. Wishat, B.D. Sykes and F.M. Richards, J. Mol. Biol., 222 (1991) 311-333]. Therefore, if the conformational motions are minimized or excluded, the observed changes in the chemical shift can simply be related to the environmental effects. The conformation(s) of the cyclic β-turn models studied in this work has been previously reported using X-ray, NMR, circular dichroism, and (FT-IR) spectroscopic methods, as well as MD calculations. [M. Hollósi, K.E. Köver, S. Holly, L. Radics and G.D. Fasman, Biopolymers, 26 (1987) 1527-1572; A. Perczel, M. Hollósi, B.M. Foxman and G.D. Fasman, J. Am. Chem. Soc., 113 (1991) 9772-9784; and H.H. Mantsch, A. Perczel, M. Hollósi and G.D. Fasman, Biopolymers, 33 (1993) 201-207]. The backbone of the cyclo[(δ)Ava—Gly—Pro—Aaa—Gly] (where Aaa = Ser(O tBu), Ser or Thr(O tBu), and δ(Ava) is δ-aminovaleric acid) compounds was found to be rigidly incorporated in the structure and to contain two intramolecular hydrogen bonds. These β-turn models also include one (or two) "free" amide group(s) that are not involved in any type of interaction. The "water titration" of these amide groups in acetonitrile, where they are involved in various degrees of hydrogen bonding, revealed their molecular environment. Owing to the rigidity of these structures, the observed changes in the amide proton chemical shifts, during titration were attributed to their involvement in hydrogen bonding. This was confirmed by monitoring the water titration simultaneously with FT-IR spectroscopy. The phenomenon described here, with the proposed characterization of the investigated peptide/water system, comprise an improvement in the NMR method for analyzing the hydrogen bonding of small rigid peptides.

  11. Quantum entanglement between amide-I and amide-site in Davydov-Scott model

    NASA Astrophysics Data System (ADS)

    Liang, Xian-Ting; Fan, Heng

    2014-01-01

    In this paper, we firstly derive non-Markovian operator Langevin equations of the Davydov monomer in its environment. Next, we replace the equations with the c-number quantum general Langevin equations (QGLEs) by calculating statistical and quantum averages of the operator Langevin equations. Then, by using the c-number QGLEs we investigate the evolutions of the subsystems amide-I and amide-site. The evolution of a parameter θ describing quantum entanglement of the coupling subsystems with continuous variable Hamiltonian has also been investigated. It is shown that there is certain entanglement between the amide-I and amide-site in the Davydov-Scott monomer.

  12. Polymer amide in the Allende and Murchison meteorites

    NASA Astrophysics Data System (ADS)

    McGeoch, Julie E. M.; McGeoch, Malcolm W.

    2015-11-01

    It has been proposed that exothermic gas phase polymerization of amino acids can occur in the conditions of a warm dense molecular cloud to form hydrophobic polymer amide (HPA) (McGeoch and McGeoch 2014). In a search for evidence of this presolar chemistry Allende and Murchison meteorites and a volcano control were diamond burr-etched and Folch extracted for potential HPA yielding 85 unique peaks in the meteorite samples via matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI TOF/MS). The amino acids after acid hydrolysis in Allende were below the level of detection but many of the Allende peaks via the more sensitive MALDI/TOF analysis could be fitted to a polymer combination of glycine, alanine, and alpha-hydroxyglycine with high statistical significance. A similar significant fit using these three amino acids could not be applied to the Murchison data indicating more complex polymer chemistry.

  13. Amino alcohol-based degradable poly(ester amide) elastomers

    PubMed Central

    Bettinger, Christopher J.; Bruggeman, Joost P.; Borenstein, Jeffrey T.; Langer, Robert S.

    2009-01-01

    Currently available synthetic biodegradable elastomers are primarily composed of crosslinked aliphatic polyesters, which suffer from deficiencies including (1) high crosslink densities, which results in exceedingly high stiffness, (2) rapid degradation upon implantation, or (3) limited chemical moieties for chemical modification. Herein, we have developed poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate)s, a new class of synthetic, biodegradable elastomeric poly(ester amide)s composed of crosslinked networks based on an amino alcohol. These crosslinked networks feature tensile Young’s modulus on the order of 1 MPa and reversable elongations up to 92%. These polymers exhibit in vitro and in vivo biocompatibility. These polymers have projected degradation half-lives up to 20 months in vivo. PMID:18295329

  14. A novel amide stationary phase for hydrophilic interaction liquid chromatography and ion chromatography.

    PubMed

    Shen, Guobin; Zhang, Feifang; Yang, Bingcheng; Chu, Changhu; Liang, Xinmiao

    2013-10-15

    A novel amide stationary phase (ASP) for hydrophilic interaction liquid chromatography (HILIC) has been prepared via the Click chemistry method. It was based on the strategy that the amino group of Asparagine was easily transferred to the corresponding azido group and then clicked onto terminal alkyne-silica gel in the presence of Cu(I)-based catalyst. For the tested polar compounds including nucleosides and nucleic acid bases, ASP-based column has demonstrated good performance in terms of separation efficiency and column stability, and the retention mechanism was found to match well the typical HILIC retention. In addition, the ASP described here showed much better selectivity in separation of inorganic anions under ion chromatography mode relative to other kinds of commercial ASP.

  15. A novel amide stationary phase for hydrophilic interaction liquid chromatography and ion chromatography.

    PubMed

    Shen, Guobin; Zhang, Feifang; Yang, Bingcheng; Chu, Changhu; Liang, Xinmiao

    2013-10-15

    A novel amide stationary phase (ASP) for hydrophilic interaction liquid chromatography (HILIC) has been prepared via the Click chemistry method. It was based on the strategy that the amino group of Asparagine was easily transferred to the corresponding azido group and then clicked onto terminal alkyne-silica gel in the presence of Cu(I)-based catalyst. For the tested polar compounds including nucleosides and nucleic acid bases, ASP-based column has demonstrated good performance in terms of separation efficiency and column stability, and the retention mechanism was found to match well the typical HILIC retention. In addition, the ASP described here showed much better selectivity in separation of inorganic anions under ion chromatography mode relative to other kinds of commercial ASP. PMID:24054569

  16. Amide derivatives of sulfonamides and isoniazid: synthesis and biological evaluation.

    PubMed

    Husain, Asif

    2009-01-01

    In the present study, various amide derivatives of sulfanilamide, sulfamethoxazole, sulfadiazine, dapsone and isoniazid have been synthesized by condensing them with appropriate 4-oxo-4-(4-substituted phenyl)butanoic acid moiety. The compounds have been evaluated for their antiinflammatory, ulcerogenic and antibacterial activities. Their structures were established on the basis of elemental analysis, 1H NMR and mass spectral data. Some of the compounds were found to have significant antiinflammatory and antibacterial activities. Additionally, these derivatives were low in their ulcerogenic action, which is the main side effect of commonly used NSAIDs. PMID:19894647

  17. Cloning of a Novel Arylamidase Gene from Paracoccus sp. Strain FLN-7 That Hydrolyzes Amide Pesticides

    PubMed Central

    Zhang, Jun; Yin, Jin-Gang; Hang, Bao-Jian; Cai, Shu; Li, Shun-Peng

    2012-01-01

    The bacterial isolate Paracoccus sp. strain FLN-7 hydrolyzes amide pesticides such as diflubenzuron, propanil, chlorpropham, and dimethoate through amide bond cleavage. A gene, ampA, encoding a novel arylamidase that catalyzes the amide bond cleavage in the amide pesticides was cloned from the strain. ampA contains a 1,395-bp open reading frame that encodes a 465-amino-acid protein. AmpA was expressed in Escherichia coli BL21 and homogenously purified using Ni-nitrilotriacetic acid affinity chromatography. AmpA is a homodimer with an isoelectric point of 5.4. AmpA displays maximum enzymatic activity at 40°C and a pH of between 7.5 and 8.0, and it is very stable at pHs ranging from 5.5 to 10.0 and at temperatures up to 50°C. AmpA efficiently hydrolyzes a variety of secondary amine compounds such as propanil, 4-acetaminophenol, propham, chlorpropham, dimethoate, and omethoate. The most suitable substrate is propanil, with Km and kcat values of 29.5 μM and 49.2 s−1, respectively. The benzoylurea insecticides (diflubenzuron and hexaflumuron) are also hydrolyzed but at low efficiencies. No cofactor is needed for the hydrolysis activity. AmpA shares low identities with reported arylamidases (less than 23%), forms a distinct lineage from closely related arylamidases in the phylogenetic tree, and has different biochemical characteristics and catalytic kinetics with related arylamidases. The results in the present study suggest that AmpA is a good candidate for the study of the mechanism for amide pesticide hydrolysis, genetic engineering of amide herbicide-resistant crops, and bioremediation of amide pesticide-contaminated environments. PMID:22544249

  18. Peptide backbone cleavage by α-amidation is enhanced at methionine residues.

    PubMed

    Hellwig, Michael; Löbmann, Katja; Orywol, Tom

    2015-01-01

    Cleavage reactions at backbone loci are one of the consequences of oxidation of proteins and peptides. During α-amidation, the Cα -N bond in the backbone is cleaved under formation of an N-terminal peptide amide and a C-terminal keto acyl peptide. On the basis of earlier works, a facilitation of α-amidation by the thioether group of adjacent methionine side chains was proposed. This reaction was characterized by using benzoyl methionine and benzoyl alanyl methionine as peptide models. The decomposition of benzoylated amino acids (benzoyl-methionine, benzoyl-alanine, and benzoyl-methionine sulfoxide) to benzamide in the presence of different carbohydrate compounds (reducing sugars, Amadori products, and reductones) was studied during incubation for up to 48 h at 80 °C in acetate-buffered solution (pH 6.0). Small amounts of benzamide (0.3-1.5 mol%) were formed in the presence of all sugars and from all benzoylated species. However, benzamide formation was strongly enhanced, when benzoyl methionine was incubated in the presence of reductones and Amadori compounds (3.5-4.2 mol%). The reaction was found to be intramolecular, because α-amidation of a similar 4-methylbenzoylated amino acid was not enhanced in the presence of benzoyl-methionine and carbohydrate compounds. In the peptide benzoyl-alanyl-methionine, α-amidation at the methionine residue is preferred over α-amidation at the benzoyl peptide bond. We propose here a mechanism for the enhancement of α-amidation at methionine residues.

  19. Structures of Highly Twisted Amides Relevant to Amide N-C Cross-Coupling: Evidence for Ground-State Amide Destabilization.

    PubMed

    Pace, Vittorio; Holzer, Wolfgang; Meng, Guangrong; Shi, Shicheng; Lalancette, Roger; Szostak, Roman; Szostak, Michal

    2016-10-01

    Herein, we show that acyclic amides that have recently enabled a series of elusive transition-metal-catalyzed N-C activation/cross-coupling reactions are highly twisted around the N-C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N-glutarimide substituent, leading to uniformly high twist (ca. 90°) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the α-carbon atom. The (15) N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground-state twist as a blueprint for activation of amides toward N-C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non-planar amide bonds.

  20. Glutamic Acid Selective Chemical Cleavage of Peptide Bonds.

    PubMed

    Nalbone, Joseph M; Lahankar, Neelam; Buissereth, Lyssa; Raj, Monika

    2016-03-01

    Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis.

  1. Decarboxylative 1,4-Addition of α-Oxocarboxylic Acids with Michael Acceptors Enabled by Photoredox Catalysis.

    PubMed

    Wang, Guang-Zu; Shang, Rui; Cheng, Wan-Min; Fu, Yao

    2015-10-01

    Enabled by iridium photoredox catalysis, 2-oxo-2-(hetero)arylacetic acids were decarboxylatively added to various Michael acceptors including α,β-unsaturated ester, ketone, amide, aldehyde, nitrile, and sulfone at room temperature. The reaction presents a new type of acyl Michael addition using stable and easily accessible carboxylic acid to formally generate acyl anion through photoredox-catalyzed radical decarboxylation. PMID:26366608

  2. A novel aromatic carbocation-based coupling reagent for esterification and amidation reactions.

    PubMed

    Nguyen, Thanh V; Lyons, Demelza J M

    2015-02-21

    A novel tropylium-based coupling reagent has been developed to facilitate the synthesis of a series of esters, amides, lactones and peptides under mild reaction conditions. Remarkably, this reagent can be used in catalytic amounts in conjunction with a sacrificial reagent, offering a new and efficient method for nucleophilic coupling reactions of carboxylic acids.

  3. Isolation and identification of microorganisms including lactic acid bacteria and their use in microbial deacidification of wines from domestic vineyards.

    PubMed

    Drozdz, Iwona; Makarewicz, Malgorzata; Tuszyński, Tadeusz

    2013-01-01

    The aim of this study was to identify various bacteria isolated from grapes and their wines. Additionally we investigated the capacity of lactic acid bacteria for microbiological deacidification of wines produced in Poland. We have identified Oenococcus oeni, Lactobacillus acidophilus and Lactobacillus delbrueckii. During the microbial deacidification process, we observed decreases of total acidity and increases of volatile acidity, with statistically significant changes noted for O. oeni in Marechal Foch and Seyval Blanc, and for Lb. acidophilus in Frontenac. On the other hand, a statistically significant increase in pH was observed in Marechal Foch and Seyval Blanc following deacidification by O. oeni.

  4. The formation of lipid hydroperoxide-derived amide-type lysine adducts on proteins: a review of current knowledge.

    PubMed

    Kato, Yoji

    2014-01-01

    Lipid peroxidation is an important biological reaction. In particular, polyunsaturated fatty acid (PUFA) can be oxidized easily. Peroxidized lipids often react with other amines accompanied by the formation of various covalent adducts. Novel amide-type lipid-lysine adducts have been identified from an in vitro reaction mixture of lipid hydroperoxide with a protein, biological tissues exposed to conditions of oxidative stress and human urine from a healthy person. In this chapter, the current knowledge of amide type adducts is reviewed with a focus on the evaluation of functional foods and diseases with a history of discovery of hexanoyl-lysine (HEL). Although there is extensive research on HEL and other amide-type adducts, the mechanism of generation of the amide bond remains unclear. We have found that the decomposed aldehyde plus peroxide combined with a lysine moiety does not fully explain the formation of the amide-type lipid-lysine adduct that is generated by lipid hydroperoxide. Singlet oxygen or an excited state of the ketone generated from the lipid hydroperoxide may also contribute to the formation of the amide linkage. The amide-adducts may prove useful not only for the detection of oxidative stress induced by disease but also for the estimation of damage caused by an excess intake of PUFA. PMID:24374915

  5. Separation of fatty acids or methyl esters including positional and geometric isomers by alumina argentation thin-layer chromatography.

    PubMed

    Breuer, B; Stuhlfauth, T; Fock, H P

    1987-07-01

    This paper describes novel and rapid thin-layer chromatography procedures for the analysis of fatty acids and methyl esters using silver-impregnated alumina sheets. These techniques are known in most laboratories, and the equipment is readily available. The fatty acid method allows a separation of petroselinic (C18:1 delta 6c), oleic (C18:1 delta 9c), elaidic (C18:1 delta 9t), erucic (C22:1 delta 13c), and brassidic acids (C22:1 delta 13t), and the methyl ester method gives an excellent resolution with respect to the number, configuration, and position of the unsaturated centers. Sufficient separation for the subsequent ozonolysis and chromatographic quantification of isomeric C18 and C22 fatty acid methyl esters is obtained with both methods.

  6. Fatty acid composition, including CLA's isomers and cholesterol content of m. longissimus lumborum and m. semimebranosus of Katahdin, Suffolk, Katahdin x Suffolk, and Suffolk x Katahdin lambs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lipids in meat products have important human health implications. Muscle tissues from Katahdin (KK), Suffolk (SS), Katahdin x Suffolk (KS), and Suffolk x Katahdin (SS) lambs were analyzed to determine the effect of breed-type on muscle fatty acid composition, including conjugated linoleic acid (CLA)...

  7. Polyimides Containing Amide And Perfluoroisopropyl Links

    NASA Technical Reports Server (NTRS)

    Dezem, James F.

    1993-01-01

    New polyimides synthesized from reactions of aromatic hexafluoroisopropyl dianhydrides with asymmetric amide diamines. Soluble to extent of at least 10 percent by weight at temperature of about 25 degrees C in common amide solvents such as N-methylpyrrolidone, N,N-dimethylacetamide, and N,N-dimethylformamide. Polyimides form tough, flexible films, coatings, and moldings. Glass-transition temperatures ranged from 300 to 365 degrees C, and crystalline melting temperatures observed between 543 and 603 degrees C. Display excellent physical, chemical, and electrical properties. Useful as adhesives, laminating resins, fibers, coatings for electrical and decorative purposes, films, wire enamels, and molding compounds.

  8. Cu(I) complexes of phosphorous amides

    SciTech Connect

    Nifant'ev, E.E.; Antipin, M.Y.; Blokhin, V.I.; Teleshev, A.T.

    1985-11-01

    The authors prepare and investigate copper complexes of phosphorous amides. The IR spectra of the systems investigated contain an absorption band at 920-940 cm/sup -1/ corresponding to P-N vibrations. The coordinates of the nonhydrogen atoms and their isotropic equivalent temperature factors are given with bond lengths and angles. The general form of the molecule of (IId) with the numbering of atoms, which are represented as probability ellipsoids of the thermal vibrations is shown. Copper complexes of phosphorus amides are phosphorylating agents for mono- and di-hydric alcohols.

  9. Composition of the epicuticular waxes coating the adaxial side of Phyllostachys aurea leaves: Identification of very-long-chain primary amides.

    PubMed

    Racovita, Radu C; Jetter, Reinhard

    2016-10-01

    The present study presents comprehensive chemical analyses of cuticular wax mixtures of the bamboo Phyllostachys aurea. The epicuticular and intracuticular waxes were sampled selectively from the adaxial side of leaves on young and old plants and investigated by gas chromatography-mass spectrometry and flame ionization detection. The epi- and intracuticular layers on young and old leaves had wax loads ranging from 1.7 μg/cm(2) to 1.9 μg/cm(2). Typical very-long-chain aliphatic wax constituents were found with characteristic chain length patterns, including alkyl esters (primarily C48), alkanes (primarily C29), fatty acids (primarily C28 and C16), primary alcohols (primarily C28) and aldehydes (primarily C30). Alicyclic wax components were identified as tocopherols and triterpenoids, including substantial amounts of triterpenoid esters. Alkyl esters, alkanes, fatty acids and aldehydes were found in greater amounts in the epicuticular layer, while primary alcohols and most terpenoids accumulated more in the intracuticular wax. Alkyl esters occurred as mixtures of metamers, combining C20 alcohol with various acids into shorter ester homologs (C36C40), and a wide range of alcohols with C22 and C24 acids into longer esters (C42C52). Primary amides were identified, with a characteristic chain length profile peaking at C30. The amides were present exclusively in the epicuticular layer and thus at or near the surface, where they may affect plant-herbivore or plant-pathogen interactions. PMID:27402630

  10. Catalytic asymmetric direct-type 1,4-addition reactions of simple amides.

    PubMed

    Suzuki, Hirotsugu; Sato, Io; Yamashita, Yasuhiro; Kobayashi, Shū

    2015-04-01

    The development of catalytic asymmetric direct-type reactions of less acidic carbonyl compounds such as amides and esters has been a challenging theme in organic chemistry for decades. Here we describe the asymmetric direct 1,4-addition reactions of simple amides with α,β-unsaturated carbonyl compounds using a catalytic amount of a novel chiral catalyst consisting of a potassium base and a macrocyclic chiral crown ether. The desired 1,5-dicarbonyl compounds were obtained in high yields with excellent diastereo- and enantioselectivities. This is the first example of a highly enantioselective catalytic direct-type reaction of simple amides. In addition, the structure of the chiral potassium catalyst has been investigated by X-ray crystallographic, dynamic (1)H NMR, and MALDI-TOF MS analyses.

  11. Solvent and conformation dependence of amide I vibrations in peptides and proteins containing proline

    NASA Astrophysics Data System (ADS)

    Roy, Santanu; Lessing, Joshua; Meisl, Georg; Ganim, Ziad; Tokmakoff, Andrei; Knoester, Jasper; Jansen, Thomas L. C.

    2011-12-01

    We present a mixed quantum-classical model for studying the amide I vibrational dynamics (predominantly CO stretching) in peptides and proteins containing proline. There are existing models developed for determining frequencies of and couplings between the secondary amide units. However, these are not applicable to proline because this amino acid has a tertiary amide unit. Therefore, a new parametrization is required for infrared-spectroscopic studies of proteins that contain proline, such as collagen, the most abundant protein in humans and animals. Here, we construct the electrostatic and dihedral maps accounting for solvent and conformation effects on frequency and coupling for the proline unit. We examine the quality and the applicability of these maps by carrying out spectral simulations of a number of peptides with proline in D2O and compare with experimental observations.

  12. Synthesis and characterization of ester and amide derivatives of titanium(IV) carboxymethylphosphonate

    NASA Astrophysics Data System (ADS)

    Melánová, Klára; Beneš, Ludvík; Trchová, Miroslava; Svoboda, Jan; Zima, Vítězslav

    2013-06-01

    A set of layered ester and amide derivatives of titanium(IV) carboxymethylphosphonate was prepared by solvothermal treatment of amorphous titanium(IV) carboxymethylphosphonate with corresponding 1-alkanols, 1,ω-alkanediols, 1-aminoalkanes, 1,ω-diaminoalkanes and 1,ω-amino alcohols and characterized by powder X-ray diffraction, IR spectroscopy and thermogravimetric analysis. Whereas alkyl chains with one functional group form bilayers tilted to the layers, 1,ω-diaminoalkanes and most of 1,ω-alkanediols form bridges connecting the adjacent layers. In the case of amino alcohols, the alkyl chains form bilayer and either hydroxyl or amino group is used for bonding. This simple method for the synthesis of ester and amide derivatives does not require preparation of acid chloride derivative as a precursor or pre-intercalation with alkylamines and can be used also for the preparation of ester and amide derivatives of titanium carboxyethylphosphonate and zirconium carboxymethylphosphonate.

  13. Rapid identification of triterpenoid sulfates and hydroxy fatty acids including two new constituents from Tydemania expeditionis by LC-MS

    PubMed Central

    Zhang, Jian-Long; Kubanek, Julia; Hay, Mark E.; Aalbersberg, William; Ye, Wen-Cai; Jiang, Ren-Wang

    2011-01-01

    Tydemania expeditionis Weber-van Bosse (Udoteaceae) is a weakly calcified green alga. In the present paper, liquid chromatography coupled with photodiode array detection and electrospray mass spectrometry was developed to identify the fingerprint components. A total of four triterpenoid sulfates and three hydroxy fatty acids in the ethyl acetate fraction of the crude extract were structurally characterized on the basis of retention time, online UV spectrum and mass fragmentation pattern. Furthermore, detailed LC-MS analysis revealed two new hydroxy fatty acids, which were then prepared and characterized by extensive NMR analyses. The proposed method provides a scientific and technical platform for the rapid identification of triterpenoid sulfates and hydroxy fatty acids in similar marine algae and terrestrial plants. PMID:21915955

  14. Fatty acid composition of ruminal digesta and longissimus muscle from lambs fed silage mixtures including red clover, sainfoin, and timothy.

    PubMed

    Campidonico, L; Toral, P G; Priolo, A; Luciano, G; Valenti, B; Hervás, G; Frutos, P; Copani, G; Ginane, C; Niderkorn, V

    2016-04-01

    This work investigated the effects of feeding silage mixtures of a plant containing polyphenol oxidase (PPO; red clover [; RC]), a plant containing tannins (sainfoin [; SF]), and a grass species not containing these compounds (timothy [; T]) on ruminal and intramuscular (i.m.) fatty acids of lambs. Forty 4-mo-old castrated male Romane lambs, divided into 5 groups, received 1 of the following silages: 1) T (100%), 2) a binary mixture of timothy and tannin-containing sainfoin ( cv. Perly; 50:50 [T-SF]), 3) a binary mixture of timothy and PPO-containing red clover ( cv. Mervius; 50:50 [T-RC]), 4) a ternary mixture of timothy, sainfoin, and red clover containing both tannins and PPO (50:25:25, respectively [T-SF-RC]), and 5) a binary mixture of tannin-containing sainfoin and PPO-containing red clover (50:50 [SF-RC]). In the rumen digesta, the partial or total replacement of T with forage legumes was associated with greater concentrations of PUFA ( < 0.001) and 1esser concentrations of MUFA ( < 0.001). The inclusion of forage legumes in the silage favored the accumulation of 18:3 -3 ( < 0.001), with the greatest concentrations being observed in SF-RC. This latter diet also led to the greatest percentage of 18:2 -6 ( < 0.001). Forage legumes decreased the -11 18:1 to 30% of T in rumen digesta ( < 0.001). Forage legumes decreased the total concentration of branched-chain fatty acids in the rumen digesta (on average, -28%; < 0.001), this effect being less marked (-17%; = 0.014) in T-RC in comparison with T. The dietary treatment tended to affect the proportion of MUFA ( = 0.081) and of PUFA ( = 0.079) in the i.m. fat of the LM, respectively, at the highest and lowest numerical value in the T group. The sum of -3 fatty acids was less in the T and T-SF groups compared with the mixture of legumes without T (SF-RC; < 0.001 and < 0.008, respectively). The latter group had also a lesser -6-to--3 ratio than the T-SF group ( = 0.01). -11 18:1 was greater ( < 0.03) in lambs given T

  15. Fatty acid composition of ruminal digesta and longissimus muscle from lambs fed silage mixtures including red clover, sainfoin, and timothy.

    PubMed

    Campidonico, L; Toral, P G; Priolo, A; Luciano, G; Valenti, B; Hervás, G; Frutos, P; Copani, G; Ginane, C; Niderkorn, V

    2016-04-01

    This work investigated the effects of feeding silage mixtures of a plant containing polyphenol oxidase (PPO; red clover [; RC]), a plant containing tannins (sainfoin [; SF]), and a grass species not containing these compounds (timothy [; T]) on ruminal and intramuscular (i.m.) fatty acids of lambs. Forty 4-mo-old castrated male Romane lambs, divided into 5 groups, received 1 of the following silages: 1) T (100%), 2) a binary mixture of timothy and tannin-containing sainfoin ( cv. Perly; 50:50 [T-SF]), 3) a binary mixture of timothy and PPO-containing red clover ( cv. Mervius; 50:50 [T-RC]), 4) a ternary mixture of timothy, sainfoin, and red clover containing both tannins and PPO (50:25:25, respectively [T-SF-RC]), and 5) a binary mixture of tannin-containing sainfoin and PPO-containing red clover (50:50 [SF-RC]). In the rumen digesta, the partial or total replacement of T with forage legumes was associated with greater concentrations of PUFA ( < 0.001) and 1esser concentrations of MUFA ( < 0.001). The inclusion of forage legumes in the silage favored the accumulation of 18:3 -3 ( < 0.001), with the greatest concentrations being observed in SF-RC. This latter diet also led to the greatest percentage of 18:2 -6 ( < 0.001). Forage legumes decreased the -11 18:1 to 30% of T in rumen digesta ( < 0.001). Forage legumes decreased the total concentration of branched-chain fatty acids in the rumen digesta (on average, -28%; < 0.001), this effect being less marked (-17%; = 0.014) in T-RC in comparison with T. The dietary treatment tended to affect the proportion of MUFA ( = 0.081) and of PUFA ( = 0.079) in the i.m. fat of the LM, respectively, at the highest and lowest numerical value in the T group. The sum of -3 fatty acids was less in the T and T-SF groups compared with the mixture of legumes without T (SF-RC; < 0.001 and < 0.008, respectively). The latter group had also a lesser -6-to--3 ratio than the T-SF group ( = 0.01). -11 18:1 was greater ( < 0.03) in lambs given T

  16. Evaluation of a novel food composition database that includes glutamine and other amino acids derived from gene sequencing data

    PubMed Central

    Lenders, CM; Liu, S; Wilmore, DW; Sampson, L; Dougherty, LW; Spiegelman, D; Willett, WC

    2011-01-01

    Objectives To determine the content of glutamine in major food proteins. Subjects/Methods We used a validated 131-food item food frequency questionnaire (FFQ) to identify the foods that contributed the most to protein intake among 70 356 women in the Nurses’ Health Study (NHS, 1984). The content of glutamine and other amino acids in foods was calculated based on protein fractions generated from gene sequencing methods (Swiss Institute of Bioinformatics) and compared with data from conventional (USDA) and modified biochemical (Khun) methods. Pearson correlation coefficients were used to compare the participants’ dietary intakes of amino acids by sequencing and USDA methods. Results The glutamine content varied from 0.01 to to 9.49 g/100 g of food and contributed from 1 to to 33% of total protein for all FFQ foods with protein. When comparing the sequencing and Kuhn’s methods, the proportion of glutamine in meat was 4.8 vs 4.4%. Among NHS participants, mean glutamine intake was 6.84 (s.d.=2.19) g/day and correlation coefficients for amino acid between intakes assessed by sequencing and USDA methods ranged from 0.94 to 0.99 for absolute intake, −0.08 to 0.90 after adjusting for 100 g of protein, and 0.88 to 0.99 after adjusting for 1000 kcal. The between-person coefficient of variation of energy-adjusted intake of glutamine was 16%. Conclusions These data suggest that (1) glutamine content can be estimated from gene sequencing methods and (2) there is a reasonably wide variation in energy-adjusted glutamine intake, allowing for exploration of glutamine consumption and disease. PMID:19756030

  17. Effects of indole amides on lettuce and onion germination and growth.

    PubMed

    Borgati, Thiago F; Boaventura, Maria Amelia D

    2011-01-01

    Auxins, such as indole-3-acetic acid (IAA), are important in plant germination and growth, while physiological polyamines, such as putrescine, are involved in cell proliferation and differentiation, and their concentrations increase during germination. In this work, novel indole amides were synthesized in good yields by monoacylation of morpholine and unprotected symmetrical diamines with indole-3-carboxylic acid, a putative metabolite of IAA, possessing no auxin-like activity. These amides were tested for their effects on seed germination and growth of the radicles and shoots of Lactuca sativa (lettuce) and Allium cepa (onion) seedlings, at 100.0, 1.0, and 0.01 microM concentrations. Germination was generally stimulated, with the exception of amide 3, derived from morpholine, at 100 microM. On radicle and shoot growth, the effect of these compounds was predominantly inhibitory. Compound 3 was the best inhibitor of growth of lettuce and onion, at the highest concentration. Amides, such as propanil, among others, are described as having herbicidal activity.

  18. Liquid chromatographic resolution of amino acid esters of acyclovir including racemic valacyclovir on crown ether-based chiral stationary phases.

    PubMed

    Ahn, Seong Ae; Hyun, Myung Ho

    2015-03-01

    Valacyclovir, a potential prodrug for the treatment of patients with herpes simplex and herpes zoster, and its analogs were resolved on two chiral stationary phases (CSPs) based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 covalently bonded to silica gel. In order to find out an appropriate mobile phase condition, various mobile phases consisting of various organic modifiers in water containing various acidic modifiers were applied to the resolution of valacyclovir and its analogs. When 30% acetonitrile in water containing any of 0.05 M, 0.10 M, or 0.15 M perchloric acid was used as a mobile phase, valacyclovir and its analogs were resolved quite well on the two CSPs with the separation factors (α) in the range of 2.49 ~ 6.35 and resolutions (RS ) in the range of 2.95 ~ 12.21. Between the two CSPs, the CSP containing residual silanol protecting n-octyl groups on the silica surface was found to be better than the CSP containing residual silanol groups.

  19. DMPS-arsenic challenge test. II. Modulation of arsenic species, including monomethylarsonous acid (MMA(III)), excreted in human urine.

    PubMed

    Aposhian, H V; Zheng, B; Aposhian, M M; Le, X C; Cebrian, M E; Cullen, W; Zakharyan, R A; Ma, M; Dart, R C; Cheng, Z; Andrewes, P; Yip, L; O'Malley, G F; Maiorino, R M; Van Voorhies, W; Healy, S M; Titcomb, A

    2000-05-15

    The administration of sodium 2,3-dimercapto-1-propane sulfonate (DMPS) to humans chronically exposed to inorganic arsenic in their drinking water resulted in the increased urinary excretion of arsenic, the appearance and identification of monomethylarsonous acid (MMA(III)) in their urine, and a large decrease in the concentration and percentage of urinary dimethylarsinic acid (DMA). This is the first time that MMA(III) has been detected in the urine. In vitro biochemical experiments were then designed and performed to understand the urinary appearance of MMA(III) and decrease of DMA. The DMPS-MMA(III) complex was not active as a substrate for the MMA(III) methyltransferase. The experimental results support the hypothesis that DMPS competes with endogenous ligands for MMA(III), forming a DMPS-MMA complex that is readily excreted in the urine and points out the need for studying the biochemical toxicology of MMA(III). It should be emphasized that MMA(III) was excreted in the urine only after DMPS administration. The results of these studies raise many questions about the potential central role of MMA(III) in the toxicity of inorganic arsenic and to the potential involvement of MMA(III) in the little-understood etiology of hyperkeratosis, hyperpigmentation, and cancer that can result from chronic inorganic arsenic exposure.

  20. Liquid chromatographic resolution of amino acid esters of acyclovir including racemic valacyclovir on crown ether-based chiral stationary phases.

    PubMed

    Ahn, Seong Ae; Hyun, Myung Ho

    2015-03-01

    Valacyclovir, a potential prodrug for the treatment of patients with herpes simplex and herpes zoster, and its analogs were resolved on two chiral stationary phases (CSPs) based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 covalently bonded to silica gel. In order to find out an appropriate mobile phase condition, various mobile phases consisting of various organic modifiers in water containing various acidic modifiers were applied to the resolution of valacyclovir and its analogs. When 30% acetonitrile in water containing any of 0.05 M, 0.10 M, or 0.15 M perchloric acid was used as a mobile phase, valacyclovir and its analogs were resolved quite well on the two CSPs with the separation factors (α) in the range of 2.49 ~ 6.35 and resolutions (RS ) in the range of 2.95 ~ 12.21. Between the two CSPs, the CSP containing residual silanol protecting n-octyl groups on the silica surface was found to be better than the CSP containing residual silanol groups. PMID:25626672

  1. Growth and development of the arborescent cactus Stenocereus queretaroensis in a subtropical semiarid environment, including effects of gibberellic acid.

    PubMed

    Pimienta, Eulogio; Hernandez, Gerardo; Domingues, Alejandro; Nobel, Park S.

    1998-01-01

    In Stenocereus queretaroensis (Weber) Buxbaum, an arborescent cactus cultivated in Jalisco, Mexico, for its fruits but studied here in wild populations, stem extension occurred in the autumn at the beginning of the dry season, flowering and fruiting occurred in the spring at the end of the dry season, and new roots grew in the summer during the wet season. The asynchrony of vegetative and reproductive growth reduces competitive sink effects, which may be advantageous for wild populations growing in infertile rocky soils. Seasonal patterns of sugars in the roots and especially the stems of S. queretaroensis were closely related to the main phenological stages, becoming lower in concentration during periods of major stem extension. Cessation of stem extension occurred in 100-year-old plants for which injection of GA(3) reinitiated such growth. Isolated chlorenchyma cylinders had maximum extension in a bathing solution containing 0.1 &mgr;M gibberellic acid.

  2. Ester-Mediated Amide Bond Formation Driven by Wet-Dry Cycles: A Possible Path to Polypeptides on the Prebiotic Earth.

    PubMed

    Forsythe, Jay G; Yu, Sheng-Sheng; Mamajanov, Irena; Grover, Martha A; Krishnamurthy, Ramanarayanan; Fernández, Facundo M; Hud, Nicholas V

    2015-08-17

    Although it is generally accepted that amino acids were present on the prebiotic Earth, the mechanism by which α-amino acids were condensed into polypeptides before the emergence of enzymes remains unsolved. Here, we demonstrate a prebiotically plausible mechanism for peptide (amide) bond formation that is enabled by α-hydroxy acids, which were likely present along with amino acids on the early Earth. Together, α-hydroxy acids and α-amino acids form depsipeptides-oligomers with a combination of ester and amide linkages-in model prebiotic reactions that are driven by wet-cool/dry-hot cycles. Through a combination of ester-amide bond exchange and ester bond hydrolysis, depsipeptides are enriched with amino acids over time. These results support a long-standing hypothesis that peptides might have arisen from ester-based precursors.

  3. Ester-Mediated Amide Bond Formation Driven by Wet-Dry Cycles: A Possible Path to Polypeptides on the Prebiotic Earth.

    PubMed

    Forsythe, Jay G; Yu, Sheng-Sheng; Mamajanov, Irena; Grover, Martha A; Krishnamurthy, Ramanarayanan; Fernández, Facundo M; Hud, Nicholas V

    2015-08-17

    Although it is generally accepted that amino acids were present on the prebiotic Earth, the mechanism by which α-amino acids were condensed into polypeptides before the emergence of enzymes remains unsolved. Here, we demonstrate a prebiotically plausible mechanism for peptide (amide) bond formation that is enabled by α-hydroxy acids, which were likely present along with amino acids on the early Earth. Together, α-hydroxy acids and α-amino acids form depsipeptides-oligomers with a combination of ester and amide linkages-in model prebiotic reactions that are driven by wet-cool/dry-hot cycles. Through a combination of ester-amide bond exchange and ester bond hydrolysis, depsipeptides are enriched with amino acids over time. These results support a long-standing hypothesis that peptides might have arisen from ester-based precursors. PMID:26201989

  4. Chlorination of N-methylacetamide and amide-containing pharmaceuticals. Quantum-chemical study of the reaction mechanism.

    PubMed

    Šakić, Davor; Šonjić, Pavica; Tandarić, Tana; Vrček, Valerije

    2014-03-27

    Chlorination of amides is of utmost importance in biochemistry and environmental chemistry. Despite the huge body of data, the mechanism of reaction between amides and hypochlorous acid in aqueous environment remains unclear. In this work, the three different reaction pathways for chlorination of N-methylacetamide by HOCl have been considered: the one-step N-chlorination of the amide, the chlorination via O-chlorinated intermediate, and the N-chlorination of the iminol intermediate. The high-level quantum chemical G3B3 composite procedure, double-hybrid B2-PLYPD, B2K-PLYP methods, and global hybrid M06-2X and BMK methods have been employed. The calculated energy barriers have been compared to the experimental value of ΔG(#)298 ≈ 87 kJ/mol, which corresponds to reaction rate constant k(r) ≈ 0.0036 M(-1) s(-1). Only the mechanism in which the iminol form of N-methylacetamide reacts with HOCl is consistent (ΔG(#)298 = 87.3 kJ/mol at G3B3 level) with experimental results. The analogous reaction mechanism has been calculated as the most favorable pathway in the chlorination of small-sized amides and amide-containing pharmaceuticals: carbamazepine, acetaminophen, and phenytoin. We conclude that the formation of the iminol intermediate followed by its reaction with HOCl is the general mechanism of N-chlorination for a vast array of amides.

  5. Skin aging and photoaging alter fatty acids composition, including 11,14,17-eicosatrienoic acid, in the epidermis of human skin.

    PubMed

    Kim, Eun Ju; Kim, Min-Kyoung; Jin, Xing-Ji; Oh, Jang-Hee; Kim, Ji Eun; Chung, Jin Ho

    2010-06-01

    We investigated the alterations of major fatty acid components in epidermis by natural aging and photoaging processes, and by acute ultraviolet (UV) irradiation in human skin. Interestingly, we found that 11,14,17-eicosatrienoic acid (ETA), which is one of the omega-3 polyunsaturated acids, was significantly increased in photoaged human epidermis in vivo and also in the acutely UV-irradiated human skin in vivo, while it was significantly decreased in intrinsically aged human epidermis. The increased ETA content in the epidermis of photoaged human skin and acute UV-irradiated human skin is associated with enhanced expression of human elongase 1 and calcium-independent phosphodiesterase A(2). We demonstrated that ETA inhibited matrix metalloproteinase (MMP)-1 expression after UV-irradiation, and that inhibition of ETA synthesis using EPTC and NA-TCA, which are elongase inhibitors, increased MMP-1 expression. Therefore, our results suggest that the UV increases the ETA levels, which may have a photoprotective effect in the human skin.

  6. Vibrational lifetimes of protein amide modes

    SciTech Connect

    Peterson, K.A.; Rella, C.A.

    1995-12-31

    Measurement of the lifetimes of vibrational modes in proteins has been achieved with a single frequency infrared pump-probe technique using the Stanford Picosecond Free-electron Laser, These are the first direct measurements of vibrational dynamics in the polyamide structure of proteins. In this study, modes associated with the protein backbone are investigated. Results for the amide I band, which consists mainly of the stretching motion of the carbonyl unit of the amide linkage, show that relaxation from the first vibrational excited level (v=1) to the vibrational ground state (v=0) occurs within 1.5 picoseconds with apparent first order kinetics. Comparison of lifetimes for myoglobin and azurin, which have differing secondary structures, show a small but significant difference. The lifetime for the amide I band of myoglobin is 300 femtoseconds shorter than for azurin. Further measurements are in progress on other backbone vibrational modes and on the temperature dependence of the lifetimes. Comparison of vibrational dynamics for proteins with differing secondary structure and for different vibrational modes within a protein will lead to a greater understanding of energy transfer and dissipation in biological systems. In addition, these results have relevance to tissue ablation studies which have been conducted with pulsed infrared lasers. Vibrational lifetimes are necessary for calculating the rate at which the energy from absorbed infrared photons is converted to equilibrium thermal energy within the irradiated volume. The very fast vibrational lifetimes measured here indicate that mechanisms which involve direct vibrational up-pumping of the amide modes with consecutive laser pulses, leading to bond breakage or weakening, are not valid.

  7. Polyimides containing amide and perfluoroisopropylidene connecting groups

    NASA Technical Reports Server (NTRS)

    Dezern, James F. (Inventor)

    1993-01-01

    New, thermooxidatively stable polyimides were prepared from the reaction of aromatic dianhydrides containing isopropylidene bridging groups with aromatic diamines containing amide connecting groups between the rings. Several of these polyimides were shown to be semi-crystalline as evidenced by wide angle x ray scattering and differential scanning calorimetry. Most of the polyimides form tough, flexible films with high tensile properties. These polyimide films exhibit enhanced solubility in organic solvents.

  8. Chromatographically separable rotamers of an unhindered amide

    PubMed Central

    Geffe, Mario; Andernach, Lars; Trapp, Oliver

    2014-01-01

    Summary Surprisingly stable formamide rotamers were encountered in the tetrahydroisoquinoline and morphinan series of alkaloids. We investigated the hindered rotation around the amide bond by dynamic high-performance liquid chromatography (DHPLC) and kinetic measurements of the interconversion of the rotamers which can readily be separated by HPLC as well as TLC. The experimental results of the different methods were compared to each other as well as to results obtained by DFT calculations. PMID:24778722

  9. Chemical Genetics Uncovers Novel Inhibitors of Lignification, Including p-Iodobenzoic Acid Targeting CINNAMATE-4-HYDROXYLASE1[OPEN

    PubMed Central

    Van de Wouwer, Dorien; Decou, Raphaël; Audenaert, Dominique; Nguyen, Long

    2016-01-01

    Plant secondary-thickened cell walls are characterized by the presence of lignin, a recalcitrant and hydrophobic polymer that provides mechanical strength and ensures long-distance water transport. Exactly the recalcitrance and hydrophobicity of lignin put a burden on the industrial processing efficiency of lignocellulosic biomass. Both forward and reverse genetic strategies have been used intensively to unravel the molecular mechanism of lignin deposition. As an alternative strategy, we introduce here a forward chemical genetic approach to find candidate inhibitors of lignification. A high-throughput assay to assess lignification in Arabidopsis (Arabidopsis thaliana) seedlings was developed and used to screen a 10-k library of structurally diverse, synthetic molecules. Of the 73 compounds that reduced lignin deposition, 39 that had a major impact were retained and classified into five clusters based on the shift they induced in the phenolic profile of Arabidopsis seedlings. One representative compound of each cluster was selected for further lignin-specific assays, leading to the identification of an aromatic compound that is processed in the plant into two fragments, both having inhibitory activity against lignification. One fragment, p-iodobenzoic acid, was further characterized as a new inhibitor of CINNAMATE 4-HYDROXYLASE, a key enzyme of the phenylpropanoid pathway synthesizing the building blocks of the lignin polymer. As such, we provide proof of concept of this chemical biology approach to screen for inhibitors of lignification and present a broad array of putative inhibitors of lignin deposition for further characterization. PMID:27485881

  10. Design, synthesis, and fungicidal activities of imino diacid analogs of valine amide fungicides.

    PubMed

    Sun, Man; Yang, Hui-Hui; Tian, Lei; Li, Jian-Qiang; Zhao, Wei-Guang

    2015-12-15

    The novel imino diacid analogs of valine amides were synthesized via several steps, including the protection, amidation, deprotection, and amino alkylation of valine, with the resulting structures confirmed by (1)H and (13)C NMR and HRMS. Bioassays showed that some of these compounds exhibited good fungicidal activity. Notably, isopropyl 2-((1-((1-(3-fluorophenyl)ethyl)amino)-3-methyl-1-oxobutan-2-yl)amino)propanoate 5i displayed significant levels of control, at 50%, against Erysiphe graminis at 3.9μM as well as a level of potency very similar to the reference azoxystrobin, which gave 60% activity at this concentration. The present work demonstrates that imino diacid analogs of valine amides could be potentially useful key compounds for the development of novel fungicides against wheat powdery mildew.

  11. The Importance of Hydrogen Bonding and Aromatic Stacking to the Affinity and Efficacy of Cannabinoid Receptor CB2 Antagonist, 5-(4-Chloro-3-methyl-phenyl)-1-(4-methyl-benzyl)-1H-pyrazole-3-carboxylic acid (1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-amide (SR144528)

    PubMed Central

    Kotsikorou, Evangelia; Navas, Frank; Roche, Michael J.; Gilliam, Anne F.; Thomas, Brian; Seltzman, Herbert H.; Kumar, Pritesh; Song, Zhao-Hui; Hurst, Dow P.; Lynch, Diane L.; Reggio, Patricia H.

    2013-01-01

    Despite the therapeutic promise of the sub-nanomolar affinity cannabinoid CB2 antagonist, N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan2-yl]-5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-1H-pyrazole-3-carboxamide (SR144528, 1), little is known about its binding site interactions and no primary interaction site for 1 at CB2 has been identified. We report here the results of Glide docking studies in our cannabinoid CB2 inactive state model that were then tested via compound synthesis, binding and functional assays. Our results show that the amide functional group of 1 is critical to its CB2 affinity and efficacy and that aromatic stacking interactions in the TMH5/6 aromatic cluster of CB2 are also important. Molecular modifications that increased the positive electrostatic potential in the region between the fenchyl and aromatic rings led to more efficacious compounds. This result is consistent with the EC-3 loop negatively charged amino acid, D275 (identified via Glide docking studies) acting as the primary interaction site for 1 and its analogs. PMID:23855811

  12. Catalytic Ester–Amide Exchange Using Group (IV) Metal Alkoxide–Activator Complexes

    PubMed Central

    Han, Chong; Lee, Jonathan P.; Lobkovsky, Emil; Porco, John A.

    2005-01-01

    A process for preparation of amides from unactivated esters and amines has been developed using a catalytic system comprised of group (IV) metal alkoxides in conjunction with additives including 1-hydroxy-7-azabenzotriazole (HOAt). In general, ester–amide exchange proceeds using a variety of structurally diverse esters and amines without azeotropic reflux to remove the alcohol byproduct. Initial mechanistic studies on the Zr(Ot-Bu)4–HOAt system revealed that the active catalyst is a novel, dimeric zirconium complex as determined by X-ray crystallography. PMID:16011366

  13. Altered Plasma Lysophosphatidylcholines and Amides in Non-Obese and Non-Diabetic Subjects with Borderline-To-Moderate Hypertriglyceridemia: A Case-Control Study

    PubMed Central

    Jung, Saem; Lee, Sang-Hyun; Lee, Jong Ho

    2015-01-01

    Hypertriglyceridemia (HTG) is a risk factor for atherosclerotic cardiovascular disease (CVD). We investigated alterations in plasma metabolites associated with borderline-to-moderate HTG (triglycerides (TG) 150-500 mg/dL). Using UPLC-LTQ-Orbitrap mass spectrometry analysis, the metabolomics profiles of 111 non-diabetic and non-obese individuals with borderline-to-moderate HTG were compared with those of 111 age- and sex-matched controls with normotriglyceridemia (NTG, TG <150 mg/dL). When compared to the NTG control group, the HTG group exhibited higher plasma levels of lysophosphatidylcholines (lysoPCs), including C14:0 (q = 0.001) and C16:0 (q = 1.8E-05), and several amides, including N-ethyldodecanamide (q = 2.9E-05), N-propyldodecanamide (q = 3.5E-05), palmitoleamide (q = 2.9E-06), and palmitic amide (q = 0.019). The metabolomic profiles of the HTG group also exhibited lower plasma levels of cis-4-octenedioic acid (q<1.0E-9) and docosanamide (q = 0.002) compared with those of the NTG controls. LysoPC 16:0 and palmitoleamide emerged as the primary metabolites able to discriminate the HTG group from the NTG group in a partial least-squares discriminant analysis and were positively associated with the fasting triglyceride levels. We identified alterations in lysoPCs, amides, and cis-4-octenedioic acid among non-diabetic and non-obese individuals with borderline-to-moderate HTG. These results provide novel insights into the metabolic alterations that occur in the early metabolic stages of HTG. This information may facilitate the design of early interventions to prevent disease progression. PMID:25856314

  14. Retinoic Acid Induced 1, RAI1: A Dosage Sensitive Gene Related to Neurobehavioral Alterations Including Autistic Behavior

    PubMed Central

    Carmona-Mora, Paulina; Walz, Katherina

    2010-01-01

    Genomic structural changes, such as gene Copy Number Variations (CNVs) are extremely abundant in the human genome. An enormous effort is currently ongoing to recognize and catalogue human CNVs and their associations with abnormal phenotypic outcomes. Recently, several reports related neuropsychiatric diseases (i.e. autism spectrum disorders, schizophrenia, mental retardation, behavioral problems, epilepsy) with specific CNV. Moreover, for some conditions, both the deletion and duplication of the same genomic segment are related to the phenotype. Syndromes associated with CNVs (microdeletion and microduplication) have long been known to display specific neurobehavioral traits. It is important to note that not every gene is susceptible to gene dosage changes and there are only a few dosage sensitive genes. Smith-Magenis (SMS) and Potocki-Lupski (PTLS) syndromes are associated with a reciprocal microdeletion and microduplication within chromosome 17p11.2. in humans. The dosage sensitive gene responsible for most phenotypes in SMS has been identified: the Retinoic Acid Induced 1 (RAI1). Studies on mouse models and humans suggest that RAI1 is likely the dosage sensitive gene responsible for clinical features in PTLS. In addition, the human RAI1 gene has been implicated in several neurobehavioral traits as spinocerebellar ataxia (SCA2), schizophrenia and non syndromic autism. In this review we discuss the evidence of RAI1 as a dosage sensitive gene, its relationship with different neurobehavioral traits, gene structure and mutations, and what is known about its molecular and cellular function, as a first step in the elucidation of the mechanisms that relate dosage sensitive genes with abnormal neurobehavioral outcomes. PMID:21629438

  15. Protein Topology Determines Cysteine Oxidation Fate: The Case of Sulfenyl Amide Formation among Protein Families

    PubMed Central

    Defelipe, Lucas A.; Lanzarotti, Esteban; Gauto, Diego; Marti, Marcelo A.; Turjanski, Adrián G.

    2015-01-01

    Cysteine residues have a rich chemistry and play a critical role in the catalytic activity of a plethora of enzymes. However, cysteines are susceptible to oxidation by Reactive Oxygen and Nitrogen Species, leading to a loss of their catalytic function. Therefore, cysteine oxidation is emerging as a relevant physiological regulatory mechanism. Formation of a cyclic sulfenyl amide residue at the active site of redox-regulated proteins has been proposed as a protection mechanism against irreversible oxidation as the sulfenyl amide intermediate has been identified in several proteins. However, how and why only some specific cysteine residues in particular proteins react to form this intermediate is still unknown. In the present work using in-silico based tools, we have identified a constrained conformation that accelerates sulfenyl amide formation. By means of combined MD and QM/MM calculation we show that this conformation positions the NH backbone towards the sulfenic acid and promotes the reaction to yield the sulfenyl amide intermediate, in one step with the concomitant release of a water molecule. Moreover, in a large subset of the proteins we found a conserved beta sheet-loop-helix motif, which is present across different protein folds, that is key for sulfenyl amide production as it promotes the previous formation of sulfenic acid. For catalytic activity, in several cases, proteins need the Cysteine to be in the cysteinate form, i.e. a low pKa Cys. We found that the conserved motif stabilizes the cysteinate by hydrogen bonding to several NH backbone moieties. As cysteinate is also more reactive toward ROS we propose that the sheet-loop-helix motif and the constraint conformation have been selected by evolution for proteins that need a reactive Cys protected from irreversible oxidation. Our results also highlight how fold conservation can be correlated to redox chemistry regulation of protein function. PMID:25741692

  16. Metal Ion Binding to Polypeptides Characterized by Irmpd Spectroscopy. Metal-Amide Nitrogen Binding and the Iminol Tautomerization.

    NASA Astrophysics Data System (ADS)

    Dunbar, Robert C.; Polfer, Nicolas; Berden, Giel; Oomens, Jos

    2012-06-01

    We have recently uncovered a new binding mode for the complexation of metal ions with gas-phase peptides. Termed the iminol mode, this binding mode is adopted by strongly binding divalent metal ions including Mg2+ and Ni2+. The metal ion displaces the amide hydrogen, which moves to protonate the amide carbonyl oxygen. A spectroscopic signature of the tautomerization is the disappearance of the characteristic Amide II band normally seen in peptide ion infrared spectra. We find that in peptides up to pentapeptides, multiple iminol binding can take place, such that all amide linkages are tautomerized to the iminol form, and chelate the metal ion. However, the iminol tautomerization depends on the nature of the metal ion, as will be discussed. Spectra of the ions were acquired by irradiating the cell of the Fourier-transform ion cyclotron resonance mass spectrometer with infrared light from the FELIX laser at wavelengths in the approximate range 500 to 1900 cm-1.

  17. Solvent extraction of Sr2+ and Cs+ using protic amide-based ionic liquids

    SciTech Connect

    Dai, Sheng; Huang, Jing-Fang; Luo, Huimin

    2010-01-01

    Sixteen protic amide-based ionic liquids (ILs) derived from N,N-dimethylformamide and other protophilic amide derivatives with bis(trifluoromethanesulfonyl)imide or bis(perfluoroethylsulfonyl)imide as conjugated anions were synthesized in a one-pot reaction with very high yields. All sixteen of these protic ionic liquids (PILs) were characterized by NMR spectra, thermogravimetric analysis, and differential scanning calorimetry. These protic amide-based ionic liquids were tested as extraction solvents using dicyclohexano-18-crown-6 (DCH18C6) as an extractant for separation of Sr2+ and Cs+ from aqueous solutions. The extraction efficiencies were studied in comparison with those derived from both imidazolium-based and ammonium-based IL extraction systems. Excellent extraction efficiencies were found for a number of these ILs using DCH18C6 as an extractant. Unlike findings for imidazolium-based and ammonium-based ILs, the observed enhancement trend for the extraction efficiency associated with our amide-based ILs is not directly correlated with the enhanced hydrophilicity of the corresponding cations of the PIL system. The effects on extraction efficiencies of solution acidities, anions, and alkyl chain lengths in the cations of ILs were also investigated and reported.

  18. Conversion of amides to esters by the nickel-catalysed activation of amide C-N bonds.

    PubMed

    Hie, Liana; Fine Nathel, Noah F; Shah, Tejas K; Baker, Emma L; Hong, Xin; Yang, Yun-Fang; Liu, Peng; Houk, K N; Garg, Neil K

    2015-08-01

    Amides are common functional groups that have been studied for more than a century. They are the key building blocks of proteins and are present in a broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to the resonance stability of the amide bond. Although amides can readily be cleaved by enzymes such as proteases, it is difficult to selectively break the carbon-nitrogen bond of an amide using synthetic chemistry. Here we demonstrate that amide carbon-nitrogen bonds can be activated and cleaved using nickel catalysts. We use this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory calculations provide insight into the thermodynamics and catalytic cycle of the amide-to-ester transformation. Our results provide a way to harness amide functional groups as synthetic building blocks and are expected to lead to the further use of amides in the construction of carbon-heteroatom or carbon-carbon bonds using non-precious-metal catalysis. PMID:26200342

  19. Conversion of amides to esters by the nickel-catalysed activation of amide C-N bonds

    NASA Astrophysics Data System (ADS)

    Hie, Liana; Fine Nathel, Noah F.; Shah, Tejas K.; Baker, Emma L.; Hong, Xin; Yang, Yun-Fang; Liu, Peng; Houk, K. N.; Garg, Neil K.

    2015-08-01

    Amides are common functional groups that have been studied for more than a century. They are the key building blocks of proteins and are present in a broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to the resonance stability of the amide bond. Although amides can readily be cleaved by enzymes such as proteases, it is difficult to selectively break the carbon-nitrogen bond of an amide using synthetic chemistry. Here we demonstrate that amide carbon-nitrogen bonds can be activated and cleaved using nickel catalysts. We use this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory calculations provide insight into the thermodynamics and catalytic cycle of the amide-to-ester transformation. Our results provide a way to harness amide functional groups as synthetic building blocks and are expected to lead to the further use of amides in the construction of carbon-heteroatom or carbon-carbon bonds using non-precious-metal catalysis.

  20. Optimal hematologic variables for oxygen transport, including P50, hemoglobin cooperativity, hematocrit, acid-base status, and cardiac function.

    PubMed

    Winslow, R M

    1988-01-01

    The two important blood properties that affect O2 delivery are the O2 equilibrium curve (OEC) and blood viscosity with its subsequent effect on flow (cardiac output). To quantitate these properties blood OEC's were analyzed in terms of the Adair 4-step oxygenation model and the resulting parameters were used to construct a computer nomogram to reproduce the OEC at any combination of effectors that regulate P50 (pH, PCO2, and 2,3-DPG). In this way, the P50 could be changed systematically and the effects on overall O2 transport could be studied. Hematocrit-viscosity-cardiac output relationships were taken from the literature and validated using data from human subjects with various pathological states and high-altitude natives. A model was then developed, using the Bohr integration, to predict the O2 transport function of blood under a variety of conditions including exercise and hypoxia. The results indicate that the optimal hematocrit is about 43-45%, even in hypoxia. The optimal P50, however, depends on the availability of O2: a high P50 is not necessarily beneficial in hypoxia and high cardiac output states. This model and general approach should prove useful in the design of blood substitutes.

  1. Phenazinium salt-catalyzed aerobic oxidative amidation of aromatic aldehydes.

    PubMed

    Leow, Dasheng

    2014-11-01

    Amides are prevalent in organic synthesis. Developing an efficient synthesis that avoids expensive oxidants and heating is highly desirable. Here the oxidative amidation of aromatic aldehydes is reported using an inexpensive metal-free visible light photocatalyst, phenazine ethosulfate, at low catalytic loading (1-2 mol %). The reaction proceeds at ambient temperature and uses air as the sole oxidant. The operationally easy procedure provides an economical, green, and mild alternative for the formation of amide bonds.

  2. Amide-Substituted Titanocenes in Hydrogen-Atom Transfer Catalysis.

    PubMed

    Zhang, Yong-Qiang; Jakoby, Verena; Stainer, Katharina; Schmer, Alexander; Klare, Sven; Bauer, Mirko; Grimme, Stefan; Cuerva, Juan Manuel; Gansäuer, Andreas

    2016-01-22

    Two new catalytic systems for hydrogen-atom transfer (HAT) catalysis involving the N-H bonds of titanocene(III) complexes with pendant amide ligands are reported. In a monometallic system, a bifunctional catalyst for radical generation and reduction through HAT catalysis depending on the coordination of the amide ligand is employed. The pendant amide ligand is used to activate Crabtree's catalyst to yield an efficient bimetallic system for radical generation and HAT catalysis. PMID:26636435

  3. Omega-3 fatty acid concentrate from Dunaliella salina possesses anti-inflammatory properties including blockade of NF-κB nuclear translocation.

    PubMed

    Chitranjali, T; Anoop Chandran, P; Muraleedhara Kurup, G

    2015-02-01

    The health benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFA), mainly eicosapentaenoic acid (EPA 20:5) and docosahexaenoic acid (DHA, 22:6), have been long known. Although various studies have demonstrated the health benefits of ω-3 PUFA, the mechanisms of action of ω-3 PUFAs are still not completely understood. While the major commercial source is marine fish oil, in this study we suggest the marine micro algae, Dunaliella salina as an alternate source of omega-3 fatty acids. Treatment with this algal omega-3 fatty acid concentrate (Ds-ω-3 FA) resulted in significant down-regulation of LPS-induced production of TNF-α and IL-6 by peripheral blood mononuclear cells (PBMCs). The concentrate was also found to be a potent blocker of cyclooxygenase (COX-2) and matrix metalloproteinase (MMP-2 and MMP-9) expression. The present study reveals the anti-inflammatory properties of Ds-ω-3 FA concentrate including the inhibition of NF-κB translocation.

  4. Nitrosation and Nitration of Fulvic Acid, Peat and Coal with Nitric Acid

    PubMed Central

    Thorn, Kevin A.; Cox, Larry G.

    2016-01-01

    Nitrohumic acids, produced from base extraction of coals and peats oxidized with nitric acid, have received considerable attention as soil ammendments in agriculture. The nitration chemistry however is incompletely understood. Moreover, there is a need to understand the reaction of nitric acid with natural organic matter (NOM) in general, in the context of a variety of environmental and biogeochemical processes. Suwannee River NOM, Suwannee River fulvic acid, and Pahokee Peat fulvic acid were treated with 15N-labeled nitric acid at concentrations ranging from 15% to 22% and analyzed by liquid and solid state 15N NMR spectroscopy. Bulk Pahokee peat and Illinois #6 coal were also treated with nitric acid, at 29% and 40% respectively, and analyzed by solid state 15N NMR spectroscopy. In addition to nitro groups from nitration of aromatic carbon, the 15N NMR spectra of all five samples exhibited peaks attributable to nitrosation reactions. These include nitrosophenol peaks in the peat fulvic acid and Suwannee River samples, from nitrosation of phenolic rings, and N-nitroso groups in the peat samples, from nitrosation of secondary amides or amines, the latter consistent with the peat samples having the highest naturally abundant nitrogen contents. Peaks attributable to Beckmann and secondary reactions of the initially formed oximes were present in all spectra, including primary amide, secondary amide, lactam, and nitrile nitrogens. The degree of secondary reaction product formation resulting from nitrosation reactions appeared to correlate inversely with the 13C aromaticities of the samples. The nitrosation reactions are most plausibly effected by nitrous acid formed from the reduction of nitric acid by oxidizable substrates in the NOM and coal samples. PMID:27175784

  5. Nitrosation and nitration of fulvic acid, peat and coal with nitric acid

    USGS Publications Warehouse

    Thorn, Kevin A.; Cox, Larry G.

    2016-01-01

    Nitrohumic acids, produced from base extraction of coals and peats oxidized with nitric acid, have received considerable attention as soil ammendments in agriculture. The nitration chemistry however is incompletely understood. Moreover, there is a need to understand the reaction of nitric acid with natural organic matter (NOM) in general, in the context of a variety of environmental and biogeochemical processes. Suwannee River NOM, Suwannee River fulvic acid, and Pahokee Peat fulvic acid were treated with 15N-labeled nitric acid at concentrations ranging from 15% to 22% and analyzed by liquid and solid state 15N NMR spectroscopy. Bulk Pahokee peat and Illinois #6 coal were also treated with nitric acid, at 29% and 40% respectively, and analyzed by solid state 15N NMR spectroscopy. In addition to nitro groups from nitration of aromatic carbon, the 15N NMR spectra of all five samples exhibited peaks attributable to nitrosation reactions. These include nitrosophenol peaks in the peat fulvic acid and Suwannee River samples, from nitrosation of phenolic rings, and N-nitroso groups in the peat samples, from nitrosation of secondary amides or amines, the latter consistent with the peat samples having the highest naturally abundant nitrogen contents. Peaks attributable to Beckmann and secondary reactions of the initially formed oximes were present in all spectra, including primary amide, secondary amide, lactam, and nitrile nitrogens. The degree of secondary reaction product formation resulting from nitrosation reactions appeared to correlate inversely with the 13C aromaticities of the samples. The nitrosation reactions are most plausibly effected by nitrous acid formed from the reduction of nitric acid by oxidizable substrates in the NOM and coal samples.

  6. Nitrosation and Nitration of Fulvic Acid, Peat and Coal with Nitric Acid.

    PubMed

    Thorn, Kevin A; Cox, Larry G

    2016-01-01

    Nitrohumic acids, produced from base extraction of coals and peats oxidized with nitric acid, have received considerable attention as soil ammendments in agriculture. The nitration chemistry however is incompletely understood. Moreover, there is a need to understand the reaction of nitric acid with natural organic matter (NOM) in general, in the context of a variety of environmental and biogeochemical processes. Suwannee River NOM, Suwannee River fulvic acid, and Pahokee Peat fulvic acid were treated with 15N-labeled nitric acid at concentrations ranging from 15% to 22% and analyzed by liquid and solid state 15N NMR spectroscopy. Bulk Pahokee peat and Illinois #6 coal were also treated with nitric acid, at 29% and 40% respectively, and analyzed by solid state 15N NMR spectroscopy. In addition to nitro groups from nitration of aromatic carbon, the 15N NMR spectra of all five samples exhibited peaks attributable to nitrosation reactions. These include nitrosophenol peaks in the peat fulvic acid and Suwannee River samples, from nitrosation of phenolic rings, and N-nitroso groups in the peat samples, from nitrosation of secondary amides or amines, the latter consistent with the peat samples having the highest naturally abundant nitrogen contents. Peaks attributable to Beckmann and secondary reactions of the initially formed oximes were present in all spectra, including primary amide, secondary amide, lactam, and nitrile nitrogens. The degree of secondary reaction product formation resulting from nitrosation reactions appeared to correlate inversely with the 13C aromaticities of the samples. The nitrosation reactions are most plausibly effected by nitrous acid formed from the reduction of nitric acid by oxidizable substrates in the NOM and coal samples.

  7. Enantioselective Synthesis of α-Hydroxy Amides and β-Amino Alcohols from α-Keto Amides.

    PubMed

    Mamillapalli, N Chary; Sekar, Govindasamy

    2015-12-14

    Synthesis of enantiomerically enriched α-hydroxy amides and β-amino alcohols has been accomplished by enantioselective reduction of α-keto amides with hydrosilanes. A series of α-keto amides were reduced in the presence of chiral Cu(II)/(S)-DTBM-SEGPHOS catalyst to give the corresponding optically active α-hydroxy amides with excellent enantioselectivities by using (EtO)3SiH as a reducing agent. Furthermore, a one-pot complete reduction of both ketone and amide groups of α-keto amides has been achieved using the same chiral copper catalyst followed by tetra-n-butylammonium fluoride (TBAF) catalyst in presence of (EtO)3SiH to afford the corresponding chiral β-amino alcohol derivatives. PMID:26503887

  8. Copper-catalyzed oxidative amidation of aldehydes with amine salts: synthesis of primary, secondary, and tertiary amides.

    PubMed

    Ghosh, Subhash Chandra; Ngiam, Joyce S Y; Seayad, Abdul M; Tuan, Dang Thanh; Chai, Christina L L; Chen, Anqi

    2012-09-21

    A practical method for the amidation of aldehydes with economic ammonium chloride or amine hydrochloride salts has been developed for the synthesis of a wide variety of amides by using inexpensive copper sulfate or copper(I) oxide as a catalyst and aqueous tert-butyl hydroperoxide as an oxidant. This amidation reaction is operationally straightforward and provides primary, secondary, and tertiary amides in good to excellent yields for most cases utilizing inexpensive and readily available reagents under mild conditions. In situ formation of amine salts from free amines extends the substrate scope of the reaction. Chiral amides are also synthesized from their corresponding chiral amines without detectable racemization. The practicality of this amide formation reaction has been demonstrated in an efficient synthesis of the antiarrhythmic drug N-acetylprocainamide. PMID:22894712

  9. AMID: autonomous modeler of intragenic duplication.

    PubMed

    Kummerfeld, Sarah K; Weiss, Anthony S; Fekete, Alan; Jermiin, Lars S

    2003-01-01

    Intragenic duplication is an evolutionary process where segments of a gene become duplicated. While there has been much research into whole-gene or domain duplication, there have been very few studies of non-tandem intragenic duplication. The identification of intragenically replicated sequences may provide insight into the evolution of proteins, helping to link sequence data with structure and function. This paper describes a tool for autonomously modelling intragenic duplication. AMID provides: identification of modularly repetitive genes; an algorithm for identifying repeated modules; and a scoring system for evaluating the modules' similarity. An evaluation of the algorithms and use cases are presented.

  10. Role of an amide bond for self-assembly of surfactants.

    PubMed

    Bordes, Romain; Tropsch, Juergen; Holmberg, Krister

    2010-03-01

    Self-assembly in solution and adsorption at the air-water interface and at solid surfaces were investigated for two amino-acid-based surfactants with conductimetry, NMR, tensiometry, quartz crystal microbalance with monitoring of the dissipation (QCM-D), and surface plasmon resonance (SPR). The surfactants studied were sodium N-lauroylglycinate and sodium N-lauroylsarcosinate, differing only in a methyl group on the amide nitrogen for the sarcosinate. Thus, the glycinate but not the sarcosinate surfactant is capable of forming intermolecular hydrogen bonds via the amide group. It was found that the amide bond, N-methylated or not, gave a substantial contribution to the hydrophilicity of the amphiphile. The ability to form intermolecular hydrogen bonds led to tighter packing at the air-water interface and at a hydrophobic surface. It also increased the tendency for precipitation as an acid-soap pair on addition of acid. Adsorption of the surfactants at a gold surface was also investigated and gave unexpected results. The sarcosine-based surfactant seemed to give bilayer adsorption, while the glycine derivative adsorbed as a monolayer.

  11. New force field parameters for metalloproteins I: Divalent copper ion centers including three histidine residues and an oxygen-ligated amino acid residue.

    PubMed

    Wise, Olivia; Coskuner, Orkid

    2014-06-30

    Transition metal ion complexation with proteins is ubiquitous across such diverse fields as neurodegenerative and cardiovascular diseases and cancer. In this study, the structures of divalent copper ion centers including three histidine and one oxygen-ligated amino acid residues and the relative binding affinities of the oxygen-ligated amino acid residues with these metal ion centers, which are debated in the literature, are presented. Furthermore, new force field parameters, which are currently lacking for the full-length metal-ligand moieties, are developed for metalloproteins that have these centers. These new force field parameters enable investigations of metalloproteins possessing these binding sites using molecular simulations. In addition, the impact of using the atom equivalence and inequivalence atomic partial charge calculation procedures on the simulated structures of these metallopeptides, including hydration properties, is described.

  12. Immobilization of lysozyme-cellulose amide-linked conjugates on cellulose i and ii cotton nanocrystalline preparations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lysozyme was attached through an amide linkage between some of the protein’s aspartate and glutamate residues to amino-glycine-cellulose (AGC), which was prepared by esterification of glycine to preparations of cotton nanocrystals (CNC). The nanocrystalline preparations were produced through acid h...

  13. Immobilization of lysozyme-cellulose amide-linked conjugates on cellulose I and II cotton nanocrystalline preparations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lysozyme was attached through an amide linkage between protein aspartate and glutamate residues to amino-glycine-cellulose (AGC), which was prepared by esterification of glycine to preparations of cotton nanocrystals (CNC). The nanocrystalline preparations were produced through acid hydrolysis and ...

  14. Conversion of Amides to Esters by the Nickel-Catalyzed Activation of Amide C–N Bonds

    PubMed Central

    Hie, Liana; Fine Nathel, Noah F.; Shah, Tejas K.; Baker, Emma L.; Hong, Xin; Yang, Yun-Fang; Liu, Peng; Houk, K. N.; Garg, Neil K.

    2015-01-01

    Amides are common functional groups that have been well studied for more than a century.1 They serve as the key building blocks of proteins and are present in an broad range of other natural and synthetic compounds. Amides are known to be poor electrophiles, which is typically attributed to resonance stability of the amide bond.1,2 Whereas Nature can easily cleave amides through the action of enzymes, such as proteases,3 the ability to selectively break the C–N bond of an amide using synthetic chemistry is quite difficult. In this manuscript, we demonstrate that amide C–N bonds can be activated and cleaved using nickel catalysts. We have used this methodology to convert amides to esters, which is a challenging and underdeveloped transformation. The reaction methodology proceeds under exceptionally mild reaction conditions, and avoids the use of a large excess of an alcohol nucleophile. Density functional theory (DFT) calculations provide insight into the thermodynamics and catalytic cycle of this unusual transformation. Our results provide a new strategy to harness amide functional groups as synthons and are expected fuel the further use of amides for the construction of carbon–heteroatom or carbon–carbon bonds using non-precious metal catalysis. PMID:26200342

  15. Extension of a PBPK model for ethylene glycol and glycolic acid to include the competitive formation and clearance of metabolites associated with kidney toxicity in rats and humans

    SciTech Connect

    Corley, R.A.; Saghir, S.A.; Bartels, M.J.; Hansen, S.C.; Creim, J.; McMartin, K.E.; Snellings, W.M.

    2011-02-01

    A previously developed PBPK model for ethylene glycol and glycolic acid was extended to include glyoxylic acid, oxalic acid, and the precipitation of calcium oxalate that is associated with kidney toxicity in rats and humans. The development and evaluation of the PBPK model was based upon previously published pharmacokinetic studies coupled with measured blood and tissue partition coefficients and rates of in vitro metabolism of glyoxylic acid to oxalic acid, glycine and other metabolites using primary hepatocytes isolated from male Wistar rats and humans. Precipitation of oxalic acid with calcium in the kidneys was assumed to occur only at concentrations exceeding the thermodynamic solubility product for calcium oxalate. This solubility product can be affected by local concentrations of calcium and other ions that are expressed in the model using an ion activity product estimated from toxicity studies such that calcium oxalate precipitation would be minimal at dietary exposures below the NOAEL for kidney toxicity in the sensitive male Wistar rat. The resulting integrated PBPK predicts that bolus oral or dietary exposures to ethylene glycol would result in typically 1.4-1.6-fold higher peak oxalate levels and 1.6-2-fold higher AUC's for calcium oxalate in kidneys of humans as compared with comparably exposed male Wistar rats over a dose range of 1-1000 mg/kg. The converse (male Wistar rats predicted to have greater oxalate levels in the kidneys than humans) was found for inhalation exposures although no accumulation of calcium oxalate is predicted to occur until exposures are well in excess of the theoretical saturated vapor concentration of 200 mg/m{sup 3}. While the current model is capable of such cross-species, dose, and route-of-exposure comparisons, it also highlights several areas of potential research that will improve confidence in such predictions, especially at low doses relevant for most human exposures.

  16. Plasma and intestinal concentrations of GIP and GLP-1 (7-36) amide during suckling and after weaning in pigs.

    PubMed

    Knapper, J M; Morgan, L M; Fletcher, J M; Marks, V

    1995-11-01

    Plasma concentrations of glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(7-36)amide (GLP-1[7-36]amide) were measured after milk ingestion in 15-18 day old piglets and after weaning diet ingestion in 33 day old piglets weaned at 21 days. Intestinal concentrations of these two hormones were also measured in unsuckled piglets of less than 24 h of age, and piglets whose ages corresponded with those used for plasma measurements. Suckling piglets showed a moderate glycaemic and insulinaemic response to milk ingestion. Plasma GIP and GLP-1(7-36)amide levels were significantly elevated at 1 and 3-h post-prandially. Weaned piglets showed a much more marked glucose and insulin response to meal ingestion. Plasma GIP and GLP-1(7-36)amide levels were again significantly elevated at 1 and 3 h in these animals. The mean plasma GIP response was greater in the weaned animals compared with the suckling animals at the time points investigated. The plasma GLP-1(7-36)amide response in contrast was significantly greater at 1 h in the suckling animals. In comparison, GIP concentrations in acid ethanol extracts of the small intestine were significantly higher during suckling and GLP-1(7-36)amide concentrations significantly higher after weaning. The circulating levels of both hormones seen during suckling and after weaning were far higher than those previously reported in humans. We conclude that both milk ingestion and the weaning diet are capable of stimulating GIP and GLP-1(7-36)amide in piglets and suggest that the levels of both hormones seen in this study may be important in adipose tissue metabolism at this time.

  17. Structures of Plutonium(IV) and Uranium(VI) with N,N-Dialkyl Amides from Crystallography, X-ray Absorption Spectra, and Theoretical Calculations.

    PubMed

    Acher, Eléonor; Hacene Cherkaski, Yanis; Dumas, Thomas; Tamain, Christelle; Guillaumont, Dominique; Boubals, Nathalie; Javierre, Guilhem; Hennig, Christoph; Solari, Pier Lorenzo; Charbonnel, Marie-Christine

    2016-06-01

    The structures of plutonium(IV) and uranium(VI) ions with a series of N,N-dialkyl amides ligands with linear and branched alkyl chains were elucidated from single-crystal X-ray diffraction (XRD), extended X-ray absorption fine structure (EXAFS), and theoretical calculations. In the field of nuclear fuel reprocessing, N,N-dialkyl amides are alternative organic ligands to achieve the separation of uranium(VI) and plutonium(IV) from highly concentrated nitric acid solution. EXAFS analysis combined with XRD shows that the coordination structure of U(VI) is identical in the solution and in the solid state and is independent of the alkyl chain: two amide ligands and four bidentate nitrate ions coordinate the uranyl ion. With linear alkyl chain amides, Pu(IV) also adopt identical structures in the solid state and in solution with two amides and four bidentate nitrate ions. With branched alkyl chain amides, the coordination structure of Pu(IV) was more difficult to establish unambiguously from EXAFS. Density functional theory (DFT) calculations were consequently performed on a series of structures with different coordination modes. Structural parameters and Debye-Waller factors derived from the DFT calculations were used to compute EXAFS spectra without using fitting parameters. By using this methodology, it was possible to show that the branched alkyl chain amides form partly outer-sphere complexes with protonated ligands hydrogen bonded to nitrate ions. PMID:27171842

  18. Presence and characterization of glucagon-like peptide-1(7-36) amide receptors in solubilized membranes of rat adipose tissue.

    PubMed

    Valverde, I; Mérida, E; Delgado, E; Trapote, M A; Villanueva-Peñacarrillo, M L

    1993-01-01

    Specific binding of [125I]glucagon-like peptide-1(7-36)amide ([125I]GLP-1(7-36)amide) to solubilized rat adipose tissue membranes was found to be dependent on temperature, time, and membrane protein concentration and readily dissociated. GLP-1(1-36)amide, GLP-2, or glucagon (10(-6) M) did not compete with [125I]GLP-1(7-36)amide binding. Half-maximal binding was achieved with 8 x 10(-10) M unlabeled GLP-1(7-36)amide, and the Scatchard plot revealed the presence of high and low affinity binding sites with Kd values of approximately 0.6 and 20 nM, respectively. The binding capacity of [125I]GLP-1(7-36)amide was about 3 times higher than that of [125I]glucagon, while the high affinity Kd and the half-maximal binding of the two peptides were similar. The presence and abundance of GLP-1(7-36)amide receptors in fat tissue together with the previous findings that the peptide stimulates glycerol and cAMP production in rat adipocytes and stimulates fatty acid synthesis in explants of rat adipose tissue open the possibility that this insulinotropic intestinal peptide may also be involved in the regulation of lipid metabolism in health and disease.

  19. Nickel-Catalyzed Reductive Amidation of Unactivated Alkyl Bromides.

    PubMed

    Serrano, Eloisa; Martin, Ruben

    2016-09-01

    A user-friendly, nickel-catalyzed reductive amidation of unactivated primary, secondary, and tertiary alkyl bromides with isocyanates is described. This catalytic strategy offers an efficient synthesis of a wide range of aliphatic amides under mild conditions and with an excellent chemoselectivity profile while avoiding the use of stoichiometric and sensitive organometallic reagents. PMID:27357076

  20. Anandamide hydrolysis in FAAH reveals a dual strategy for efficient enzyme-assisted amide bond cleavage via nitrogen inversion.

    PubMed

    Palermo, Giulia; Campomanes, Pablo; Cavalli, Andrea; Rothlisberger, Ursula; De Vivo, Marco

    2015-01-22

    Herein, we combined classical molecular dynamics (MD) and quantum mechanical/molecular mechanics (QM/MM) simulations to unravel the whole catalytic cycle of fatty acid amide hydrolase (FAAH) in complex with anandamide, the main neurotransmitters involved in the control of pain. While microsecond MD simulations of FAAH in a realistic membrane/water environment provided a solid model for the reactant state of the enzymatic complex (Palermo et al. J. Chem. Theory Comput. 2013, 9, 1202-1213.), QM/MM simulations depict now a highly concerted two-step catalytic mechanism characterized by (1) acyl-enzyme formation after hydrolysis of the substrate amide bond and (2) deacylation reaction with restoration of the catalytic machinery. We found that a crucial event for anandamide hydrolysis is the inversion of the reactive nitrogen of the scissile amide bond, which occurs during the acylation rate-limiting step. We show that FAAH uses an exquisite catalytic strategy to induce amide bond distortion, reactive nitrogen inversion, and amide bond hydrolysis, promoting catalysis to completion. This new strategy is likely to be of general applicability to other amidases/peptidases that show similar catalytic site architectures, providing crucial insights for de novo enzyme design or drug discovery efforts.

  1. Targeted mutation of Δ12 and Δ15 desaturase genes in hemp produce major alterations in seed fatty acid composition including a high oleic hemp oil.

    PubMed

    Bielecka, Monika; Kaminski, Filip; Adams, Ian; Poulson, Helen; Sloan, Raymond; Li, Yi; Larson, Tony R; Winzer, Thilo; Graham, Ian A

    2014-06-01

    We used expressed sequence tag library and whole genome sequence mining to identify a suite of putative desaturase genes representing the four main activities required for production of polyunsaturated fatty acids in hemp seed oil. Phylogenetic-based classification and developing seed transcriptome analysis informed selection for further analysis of one of seven Δ12 desaturases and one of three Δ15 desaturases that we designate CSFAD2A and CSFAD3A, respectively. Heterologous expression of corresponding cDNAs in Saccharomyces cerevisiae showed CSFAD2A to have Δx+3 activity, while CSFAD3A activity was exclusively at the Δ15 position. TILLING of an ethyl methane sulphonate mutagenized population identified multiple alleles including non-sense mutations in both genes and fatty acid composition of seed oil confirmed these to be the major Δ12 and Δ15 desaturases in developing hemp seed. Following four backcrosses and sibling crosses to achieve homozygosity, csfad2a-1 was grown in the field and found to produce a 70 molar per cent high oleic acid (18:1(Δ9) ) oil at yields similar to wild type. Cold-pressed high oleic oil produced fewer volatiles and had a sevenfold increase in shelf life compared to wild type. Two low abundance octadecadienoic acids, 18:2(Δ6,9) and 18:2(Δ9,15), were identified in the high oleic oil, and their presence suggests remaining endogenous desaturase activities utilize the increased levels of oleic acid as substrate. Consistent with this, CSFAD3A produces 18:2(Δ9,15) from endogenous 18:1(Δ9) when expressed in S. cerevisiae. This work lays the foundation for the development of additional novel oil varieties in this multipurpose low input crop.

  2. Using non-invasive molecular spectroscopic techniques to detect unique aspects of protein Amide functional groups and chemical properties of modeled forage from different sourced-origins

    NASA Astrophysics Data System (ADS)

    Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

    2016-03-01

    The non-invasive molecular spectroscopic technique-FT/IR is capable to detect the molecular structure spectral features that are associated with biological, nutritional and biodegradation functions. However, to date, few researches have been conducted to use these non-invasive molecular spectroscopic techniques to study forage internal protein structures associated with biodegradation and biological functions. The objectives of this study were to detect unique aspects and association of protein Amide functional groups in terms of protein Amide I and II spectral profiles and chemical properties in the alfalfa forage (Medicago sativa L.) from different sourced-origins. In this study, alfalfa hay with two different origins was used as modeled forage for molecular structure and chemical property study. In each forage origin, five to seven sources were analyzed. The molecular spectral profiles were determined using FT/IR non-invasive molecular spectroscopy. The parameters of protein spectral profiles included functional groups of Amide I, Amide II and Amide I to II ratio. The results show that the modeled forage Amide I and Amide II were centered at 1653 cm- 1 and 1545 cm- 1, respectively. The Amide I spectral height and area intensities were from 0.02 to 0.03 and 2.67 to 3.36 AI, respectively. The Amide II spectral height and area intensities were from 0.01 to 0.02 and 0.71 to 0.93 AI, respectively. The Amide I to II spectral peak height and area ratios were from 1.86 to 1.88 and 3.68 to 3.79, respectively. Our results show that the non-invasive molecular spectroscopic techniques are capable to detect forage internal protein structure features which are associated with forage chemical properties.

  3. The use of amide local anesthetics in patients susceptible to malignant hyperthermia.

    PubMed

    Minasian, A; Yagiela, J A

    1988-10-01

    The use of amide local anesthetics in dental patients presumed to be susceptible to malignant hyperthermia (MH) is controversial. A literature review of 17 recent dental publications and their reference citations revealed that the recommendation to avoid local anesthetics of the amide type in dental treatment of MH-susceptible (MHS) patients is based on in vitro muscle investigations, unpublished communications, and a single case report suggestive of MH. Therefore, a survey of members of the Malignant Hyperthermia Association of the United States designed to determine what, if any, MH-like reactions have occurred in patients with MHS receiving dental treatment was conducted. Of a total of 307 MHS respondents, 36 (12%) reported adverse reactions to dental care. Only one respondent, however, reported symptoms suspicious of MH (fever, muscle pain) in which the administration of amide local anesthetics appeared to be closely linked. Fifty-six (18%) of the respondents have had difficulty obtaining routine dental care since being identified as MHS; this includes 27 who have been refused dental treatment or have had to undergo operative procedures without the benefit of local anesthesia. These results support the conclusions that amide local anesthetics may be administered to MHS patients without significant risk and that currently the diagnosis of MH susceptibility can adversely affect the quality of dental care. PMID:3054689

  4. Preparation and characterization of amidated pectin based hydrogels for drug delivery system.

    PubMed

    Mishra, R K; Datt, M; Pal, K; Banthia, A K

    2008-06-01

    In the current studies attempts were made to prepare hydrogels by chemical modification of pectin with ethanolamine (EA) in different proportions. Chemically modified pectin products were crosslinked with glutaraldehyde reagent for preparing hydrogels. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), organic elemental analysis, X-ray diffraction studies (XRD), swelling studies, biocompatibility and hemocompatibility studies. Mechanical properties of the prepared hydrogels were evaluated by tensile test. The hydrogels were loaded with salicylic acid (used as a model drug) and drug release studies were done in a modified Franz's diffusion cell. FTIR spectroscopy indicated the presence of primary and secondary amide absorption bands. XRD studies indicated increase in crystallinity in the hydrogels as compared to unmodified pectin. The degree of amidation (DA) and molar and mass reaction yields (YM and YN) was calculated based on the results of organic elemental analysis. The hydrogels showed good water holding properties and were found to be compatible with B-16 melanoma cells & human blood.

  5. Titanocene(III)-Catalyzed Three-Component Reaction of Secondary Amides, Aldehydes, and Electrophilic Alkenes.

    PubMed

    Zheng, Xiao; He, Jiang; Li, Heng-Hui; Wang, Ao; Dai, Xi-Jie; Wang, Ai-E; Huang, Pei-Qiang

    2015-11-01

    An umpolung Mannich-type reaction of secondary amides, aliphatic aldehydes, and electrophilic alkenes has been disclosed. This reaction features the one-pot formation of C-N and C-C bonds by a titanocene-catalyzed radical coupling of the condensation products, from secondary amides and aldehydes, with electrophilic alkenes. N-substituted γ-amido-acid derivatives and γ-amido ketones can be efficiently prepared by the current method. Extension to the reaction between ketoamides and electrophilic alkenes allows rapid assembly of piperidine skeletons with α-amino quaternary carbon centers. Its synthetic utility has been demonstrated by a facile construction of the tricyclic core of marine alkaloids such as cylindricine C and polycitorol A.

  6. Chemical shift and electric field gradient tensors for the amide and carboxyl hydrogens in the model peptide N-acetyl-D,L-valine. Single-crystal deuterium NMR study.

    SciTech Connect

    Gerald, R. E., II; Bernhard, T.; Haeberlen, U.; Rendell, J.; Opella, S.; Chemical Engineering

    1993-01-01

    Solid-state NMR spectroscopy is well established as a method for describing molecular structure with resolution on the atomic scale. Many of the NMR observables result from anisotropic interactions between the nuclear spin and its environment. These observables can be described by second-rank tensors. For example, the eigenvalues of the traceless symmetric part of the hydrogen chemical shift (CS) tensor provide information about the strength of inter- or intramolecular hydrogen bonding. On the other hand, the eigenvectors of the deuterium electric field gradient (EFG) tensor give deuteron/proton bond directions with an accuracy rivalled only by neutron diffraction. In this paper the authors report structural information of this type for the amide and carboxyl hydrogen sites in a single crystal of the model peptide N-acetyl-D,L-valine (NAV). They use deuterium NMR to infer both the EFG and CS tensors at the amide and carboxyl hydrogen sites in NAV. Advantages of this technique over multiple-pulse proton NMR are that it works in the presence of {sup 14}N spins which are very hard to decouple from protons and that additional information in form of the EFG tensors can be derived. The change in the CS and EFG tensors upon exchange of a deuteron for a proton (the isotope effect) is anticipated to be very small; the effect on the CS tensors is certainly smaller than the experimental errors. NAV has served as a model peptide before in a variety of NMR studies, including those concerned with developing solid-state NMR spectroscopy as a method for determining the structure of proteins. NMR experiments on peptide or protein samples which are oriented in at least one dimension can provide important information about the three-dimensional structure of the peptide or the protein. In order to interpret the NMR data in terms of the structure of the polypeptide, the relationship of the CS and EFG tensors to the local symmetry elements of an amino acide, e.g., the peptide plane, is

  7. Reaction of arenesulfinimidic acid derivatives with thiophenols

    SciTech Connect

    Pel'kis, N.P.; Levchenko, E.S.

    1986-07-20

    The amides and esters of N-substituted arenesulfinimidic acids are reduced by the action of thiophenols primarily to N-substituted arenesulfenamides, while the thiophenols are oxidized to the corresponding derivatives of the arenesulfinic acids.

  8. Kinetic analyses of peptidylglycine alpha-amidating monooxygenase from pancreatic islets.

    PubMed

    Noe, B D; Katopodis, A G; May, S W

    1991-08-01

    Peptidylglycine alpha-amidating monooxygenase (PAM) plays an important role in the post-translational processing of bioactive neuropeptides by participating in C-terminal amidation. We have examined PAM activity in the pancreatic islets of the anglerfish (AF), Lophius americanus. It was previously demonstrated that the cofactor requirements and pH optimum for the fish PAM are essentially identical to PAM obtained from other tissues and species. The present study was performed to examine the enzymatic characteristics of the fish islet PAM in more detail. One of the questions addressed was the suitability of the AF islet neuropeptide Y-like peptide, aPY-Gly, as a substrate for the islet PAM. Partially purified PAM from AF islet secretory granules was incubated with [125I] aPY-Gly and the resulting products were analyzed by HPLC. The islet PAM readily mediated the formation of aPY-amide from aPY-Gly. PAM purified from bovine adrenal chromaffin granules also catalyzed the amidation of [125I] aPY-Gly. The kinetic parameters of the islet PAM were examined using trinitrophenylated-D-Tyr-Val-Gly (TNP-D-YVG) and 4-nitrohippuric acid (4-NHA). The Km of the islet PAM was 25 +/- 5 microM for TNP-D-YVG and 3.4 +/- 1 mM for 4-NHA. The competitive inhibitor of mammalian PAM activity, 4-methoxybenzoxyacetic acid, proved to be a potent inhibitor of the islet PAM as well, with an apparent KI of 0.06 mM. These results demonstrate that the AF islet PAM exhibits substrate compatibility, kinetic parameters, and inhibitor susceptibility quite similar to the characteristics of PAM from other tissues and species. PMID:1916206

  9. Recyclable hypervalent iodine(III) reagent iodosodilactone as an efficient coupling reagent for direct esterification, amidation, and peptide coupling.

    PubMed

    Tian, Jun; Gao, Wen-Chao; Zhou, Dong-Mei; Zhang, Chi

    2012-06-15

    A hypervalent iodine(III) reagent plays a novel role as an efficient coupling reagent to promote the direct condensation between carboxylic acids and alcohols or amines to provide esters, macrocyclic lactones, amides, as well as peptides without racemization. The regeneration of iodosodilactone (1) can also be readily achieved. The intermediate acyloxyphosphonium ion C from the activation of a carboxylic acid is thought to be involved in the present esterification reaction.

  10. Total lipids of Sarda sheep meat that include the fatty acid and alkenyl composition and the CLA and trans-18:1 isomers.

    PubMed

    Santercole, Viviana; Mazzette, Rina; De Santis, Enrico P L; Banni, Sebastiano; Goonewardene, Laki; Kramer, John K G

    2007-04-01

    The total lipids of the longissimus dorsi muscle were analyzed from commercial adult Sarda sheep in Sardina taken from local abattoirs, and in the subsequent year from three local farms in the Sassari region that provided some information on the amount and type of supplements fed to the pasture-fed sheep. The complete lipid analysis of sheep meat included the fatty acids from O-acyl and N-acyl lipids, including the trans- and conjugated linoleic acid (CLA) isomers and the alk-1-enyl ethers from the plasmalogenic lipids. This analysis required the use of a combination of acid- and base-catalyzed methylation procedures, the former to quantitate the O-acyl, N-acyl and alkenyl ethers, and the latter to determine the content of CLA isomers and their metabolites. A combination of gas chromatographic and silver-ion separation techniques was necessary to quantitate all of the meat lipid constituents, which included a prior separation of the trans-octadecenoic acids (18:1) and a separation of fatty acid methyl esters and the dimethylacetals (DMAs) from the acyl and alk-1-enyl ethers, respectively. The alk-1-enyl moieties of the DMAs were analyzed as their stable cyclic acetals. In general, about half of the meat lipids were triacylglycerols, even though excess fat was trimmed from the meat. The higher fat content in the meat appears to be related to the older age of these animals. The variation in the trans-18:1 and CLA isomer profiles of the Sarda sheep obtained from the abattoirs was much greater than in the profiles from the sheep from the three selected farms. Higher levels of 10t-18:1, 7t9c-18:2, 9t11c-18:2 and 10t12c-18:2 were observed in the commercial sheep meat, which reflected the poorer quality diets of these sheep compared to those from the three farms, which consistently showed higher levels of 11t-18:1, 9c11t-18:2 and 11t13c-18:2. In the second study, sheep were provided with supplements during the spring and summer grazing season, which contributed to higher

  11. Thermodynamic models of aqueous solutions containing inorganic electrolytes and dicarboxylic acids at 298.15 K. 2. Systems including dissociation equilibria.

    PubMed

    Clegg, Simon L; Seinfeld, John H

    2006-05-01

    Atmospheric aerosols contain a significant fraction of water-soluble organic compounds, including dicarboxylic acids. Pitzer activity coefficient models are developed, using a wide range of data at 298.15 K, for the following systems containing succinic acid (H(2)Succ) and/or succinate salts: [H(+), Li(+), Na(+), K(+), Rb(+), Cs(+)]Cl(-)-H(2)Succ-H(2)O, HNO(3)-H(2)Succ-H(2)O, H(+)-NH(4)(+)-HSucc(-)-Succ(2-)-NH(3)-H(2)Succ-H(2)O, NH(4)Cl-(NH(4))(2)Succ-H(2)O, H(+)-Na(+)-HSucc(-)-Succ(2-)-Cl(-)-H(2)Succ-H(2)O, NH(4)NO(3)-H(2)Succ-H(2)O, and H(2)SO(4)-H(2)Succ-H(2)O. The above compositions are given in terms of ions in the cases where acid dissociation was considered. Pitzer models were also developed for the following systems containing malonic acid (H(2)Malo): H(+)-Na(+)-HMalo(-)-Malo(2-)-Cl(-)-H(2)Malo-H(2)O, and H(2)Malo-H(2)SO(4)-H(2)O. The models are used to evaluate the extended Zdanovskii-Stokes-Robinson (ZSR) model proposed by Clegg and Seinfeld (J. Phys. Chem. A 2004, 108, 1008-1017) for calculating water and solute activities in solutions in which dissociation equilibria occur. The ZSR model yields satisfactory results only for systems that contain moderate to high concentrations of (nondissociating) supporting electrolyte. A practical modeling scheme is proposed for aqueous atmospheric aerosols containing both electrolytes and dissociating (organic) nonelectrolytes.

  12. 40 CFR 721.9672 - Amides, tall-oil fatty, N-[2-[2-hydroxyethyl)amino]ethyl], reaction products with sulfur dioxide...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...], reaction products with sulfur dioxide; fatty acids, tall-oil, reaction products with 1-piperazineethanamine and sulfur dioxide; fatty acids, tall-oil reaction products with sulfur dioxide and... Specific Chemical Substances § 721.9672 Amides, tall-oil fatty, N- ethyl], reaction products with...

  13. 40 CFR 721.9672 - Amides, tall-oil fatty, N-[2-[2-hydroxyethyl)amino]ethyl], reaction products with sulfur dioxide...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...], reaction products with sulfur dioxide; fatty acids, tall-oil, reaction products with 1-piperazineethanamine and sulfur dioxide; fatty acids, tall-oil reaction products with sulfur dioxide and... Specific Chemical Substances § 721.9672 Amides, tall-oil fatty, N- ethyl], reaction products with...

  14. 40 CFR 721.9672 - Amides, tall-oil fatty, N-[2-[2-hydroxyethyl)amino]ethyl], reaction products with sulfur dioxide...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...], reaction products with sulfur dioxide; fatty acids, tall-oil, reaction products with 1-piperazineethanamine and sulfur dioxide; fatty acids, tall-oil reaction products with sulfur dioxide and... Specific Chemical Substances § 721.9672 Amides, tall-oil fatty, N- ethyl], reaction products with...

  15. 40 CFR 721.9672 - Amides, tall-oil fatty, N-[2-[2-hydroxyethyl)amino]ethyl], reaction products with sulfur dioxide...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...], reaction products with sulfur dioxide; fatty acids, tall-oil, reaction products with 1-piperazineethanamine and sulfur dioxide; fatty acids, tall-oil reaction products with sulfur dioxide and... Specific Chemical Substances § 721.9672 Amides, tall-oil fatty, N- ethyl], reaction products with...

  16. 40 CFR 721.9672 - Amides, tall-oil fatty, N-[2-[2-hydroxyethyl)amino]ethyl], reaction products with sulfur dioxide...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...], reaction products with sulfur dioxide; fatty acids, tall-oil, reaction products with 1-piperazineethanamine and sulfur dioxide; fatty acids, tall-oil reaction products with sulfur dioxide and... Specific Chemical Substances § 721.9672 Amides, tall-oil fatty, N- ethyl], reaction products with...

  17. A common set of conserved motifs in a vast variety of putative nucleic acid-dependent ATPases including MCM proteins involved in the initiation of eukaryotic DNA replication.

    PubMed

    Koonin, E V

    1993-06-11

    A new superfamily of (putative) DNA-dependent ATPases is described that includes the ATPase domains of prokaryotic NtrC-related transcription regulators, MCM proteins involved in the initiation of eukaryotic DNA replication, and a group of uncharacterized bacterial and chloroplast proteins. MCM proteins are shown to contain a modified form of the ATP-binding motif and are predicted to mediate ATP-dependent opening of double-stranded DNA in the replication origins. In a second line of investigation, it is demonstrated that the products of unidentified open reading frames from Marchantia mitochondria and from yeast, and a domain of a baculovirus protein involved in viral DNA replication are related to the superfamily III of DNA and RNA helicases that previously has been known to include only proteins of small viruses. Comparison of the multiple alignments showed that the proteins of the NtrC superfamily and the helicases of superfamily III share three related sequence motifs tightly packed in the ATPase domain that consists of 100-150 amino acid residues. A similar array of conserved motifs is found in the family of DnaA-related ATPases. It is hypothesized that the three large groups of nucleic acid-dependent ATPases have similar structure of the core ATPase domain and have evolved from a common ancestor.

  18. Chemical attributes of some clouds amid a forest ecosystem's trees

    USGS Publications Warehouse

    DeFelice, Thomas P.

    2002-01-01

    Simultaneous physical and chemical characteristics of clouds amid and above the trees of a montane forest, located about 3.3 km southwest of Mt. Mitchell, NC, were collected between 13 and 22 June 1993. This paper summarizes the chemical characteristics of the cloud droplets amid the trees. The ionic composition and pH of the analyzed amid-canopy cloud water samples are generally consistent with those of previous above-canopy cloud water samples obtained at this site. Magnesium, sodium, and calcium are highly correlated to each other amid the canopy as compared to above the canopy. Above-canopy and amid-canopy cloud-only episodes, with concurrent event-averaged cloud water pH values at or below 3.1, generally contain more magnesium, sodium, and calcium in the amid-canopy cloud water samples compared to concurrent above-canopy cloud water samples. The observed chemical differences between the amid-canopy cloud and the above- canopy cloud suggest an unhealthier environment for the tree canopy when the cloud water traversing this site has a pH value at or below 3.1. The predominant ion deposition fluxes were calculated to provide preliminary data for studies designed to explicitly quantify how the chemical composition of cloud water affects tree health. ?? 2002 Elsevier Science B.V. All rights reserved.

  19. DFT-based simulations of IR amide I' spectra for a small protein in solution. Comparison of explicit and empirical solvent models.

    PubMed

    Grahnen, Johan A; Amunson, Krista E; Kubelka, Jan

    2010-10-14

    Infrared (IR) amide I' spectra are widely used for investigations of the structural properties of proteins in aqueous solution. For analysis of the experimental data, it is necessary to separate the spectral features due to the backbone conformation from those arising from other factors, in particular the interaction with solvent. We investigate the effects of solvation on amide I' spectra for a small 40-residue helix-turn-helix protein by theoretical simulations based on density functional theory (DFT). The vibrational force fields and intensity parameters for the protein amide backbone are constructed by transfer from smaller heptaamide fragments; the side chains are neglected in the DFT calculations. Solvent is modeled at two different levels: first as explicit water hydrogen bonded to the surface amide groups, treated at the same DFT level, and, second, using the electrostatic map approach combined with molecular dynamics (MD) simulation. Motional narrowing of the spectral band shapes due to averaging over the fast solvent fluctuation is introduced by use of the time-averaging approximation (TAA). The simulations are compared with the experimental amide I', including two (13)C isotopically edited spectra, corrected for the side-chain signals. Both solvent models are consistent with the asymmetric experimental band shape, which arises from the differential solvation of the amide backbone. However, the effects of (13)C isotopic labeling are best captured by the gas-phase calculations. The limitations of the solvent models and implications for the theoretical simulations of protein amide vibrational spectra are discussed.

  20. Multi-Biomarkers for Early Detection of Type 2 Diabetes, Including 10- and 12-(Z,E)-Hydroxyoctadecadienoic Acids, Insulin, Leptin, and Adiponectin

    PubMed Central

    Umeno, Aya; Yoshino, Kohzoh; Hashimoto, Yoshiko; Shichiri, Mototada; Kataoka, Masatoshi; Yoshida, Yasukazu

    2015-01-01

    We have previously found that fasting plasma levels of totally assessed 10- and 12-(Z,E)-hydroxyoctadecadienoic acid (HODE) correlated well with levels of glycated hemoglobin (HbA1c) and glucose during oral glucose tolerance tests (OGTT); these levels were determined via liquid chromatography—mass spectrometry after reduction and saponification. However, 10- and 12-(Z,E)-HODE alone cannot perfectly detect early impaired glucose tolerance (IGT) and/or insulin resistance, which ultimately lead to diabetes. In this study, we randomly recruited healthy volunteers (n = 57) who had no known history of any diseases, and who were evaluated using the OGTT, the HODE biomarkers, and several additional proposed biomarkers, including retinol binding protein 4 (RBP4), adiponectin, leptin, insulin, glycoalbumin, and high sensitivity-C-reactive protein. The OGTT revealed that our volunteers included normal individuals (n = 44; Group N), “high-normal” individuals (fasting plasma glucose 100–109 mg/dL) with IGT (n = 11; Group HN+IGT), and diabetic individuals (n = 2; Group D). We then used these groups to evaluate the potential biomarkers for the early detection of type 2 diabetes. Plasma levels of RBP4 and glycoalbumin were higher in Group HN+IGT, compared to those in Group N, and fasting levels of 10- and 12-(Z,E)-HODE/linoleic acids were significantly correlated with levels of RBP4 (p = 0.003, r = 0.380) and glycoalbumin (p = 0.006, r = 0.316). Furthermore, we developed a stepwise multiple linear regression models to predict the individuals’ insulin resistance index (the Matsuda Index 3). Fasting plasma levels of 10- and 12-(Z,E)-HODE/linoleic acids, glucose, insulin, and leptin/adiponectin were selected as the explanatory variables for the models. The risks of type 2 diabetes, early IGT, and insulin resistance were perfectly predicted by comparing fasting glucose levels to the estimated Matsuda Index 3 (fasting levels of 10- and 12-(Z,E)-HODE/linoleic acids, insulin

  1. New organic semiconductors with imide/amide-containing molecular systems.

    PubMed

    Liu, Zitong; Zhang, Guanxin; Cai, Zhengxu; Chen, Xin; Luo, Hewei; Li, Yonghai; Wang, Jianguo; Zhang, Deqing

    2014-10-29

    Due to their high electron affinities, chemical and thermal stabilities, π-conjugated molecules with imide/amide frameworks have received considerable attentions as promising candidates for high-performance optoelectronic materials, particularly for organic semiconductors with high carrier mobilities. The purpose of this Research News is to give an overview of recent advances in development of high performance imide/amide based organic semiconductors for field-effect transistors. It covers naphthalene diimide-, perylene diimide- and amide-based conjugated molecules and polymers for organic semiconductors. PMID:24633804

  2. New organic semiconductors with imide/amide-containing molecular systems.

    PubMed

    Liu, Zitong; Zhang, Guanxin; Cai, Zhengxu; Chen, Xin; Luo, Hewei; Li, Yonghai; Wang, Jianguo; Zhang, Deqing

    2014-10-29

    Due to their high electron affinities, chemical and thermal stabilities, π-conjugated molecules with imide/amide frameworks have received considerable attentions as promising candidates for high-performance optoelectronic materials, particularly for organic semiconductors with high carrier mobilities. The purpose of this Research News is to give an overview of recent advances in development of high performance imide/amide based organic semiconductors for field-effect transistors. It covers naphthalene diimide-, perylene diimide- and amide-based conjugated molecules and polymers for organic semiconductors.

  3. Synthesis, spectroscopic and structural perspective of new ferrocenyl amides

    NASA Astrophysics Data System (ADS)

    Etter, Martin; Nigar, Asifa; Ali, Naveed Zafar; Akhter, Zareen; Dinnebier, Robert E.

    2016-05-01

    Two new ferrocene derivatives with amide linkages were synthesized by the condensation of 4-ferrocenylaniline with n-alkyl acid chloride derivatives as pristine orange solids in good yields. FTIR and 1H/13C NMR studies have confirmed the basic structure of the molecules with the involvement of intermolecular H-bonding, which together with the ferrocene-like packing ensures the stability of the crystal structure. Crystal structures for both compounds were solved by Rietveld refinements of high resolution X-ray powder diffraction data. The XRD results show that both compounds crystallize in the monoclinic space group P21/c. The primary feature of the crystal structure is a double layer of ferrocenyl groups stretched out in the b-c -plane perpendicular to the a-axis, with packing of the ferrocenyl groups occurring in a manner similar to that of pure ferrocene. Despite the close structural similarity, both compounds differ in the optimized geometry of respective Ferrocene conformers. The Cp rings are eclipsed for one Ferrocene conformer and close to staggered for the other, owing to the low energy barrier for the rotation of a cyclopentadienyl ring relative to the rest of the molecule.

  4. Enteric Bacterial Metabolites Propionic and Butyric Acid Modulate Gene Expression, Including CREB-Dependent Catecholaminergic Neurotransmission, in PC12 Cells - Possible Relevance to Autism Spectrum Disorders

    PubMed Central

    Nankova, Bistra B.; Agarwal, Raj; MacFabe, Derrick F.; La Gamma, Edmund F.

    2014-01-01

    Alterations in gut microbiome composition have an emerging role in health and disease including brain function and behavior. Short chain fatty acids (SCFA) like propionic (PPA), and butyric acid (BA), which are present in diet and are fermentation products of many gastrointestinal bacteria, are showing increasing importance in host health, but also may be environmental contributors in neurodevelopmental disorders including autism spectrum disorders (ASD). Further to this we have shown SCFA administration to rodents over a variety of routes (intracerebroventricular, subcutaneous, intraperitoneal) or developmental time periods can elicit behavioral, electrophysiological, neuropathological and biochemical effects consistent with findings in ASD patients. SCFA are capable of altering host gene expression, partly due to their histone deacetylase inhibitor activity. We have previously shown BA can regulate tyrosine hydroxylase (TH) mRNA levels in a PC12 cell model. Since monoamine concentration is known to be elevated in the brain and blood of ASD patients and in many ASD animal models, we hypothesized that SCFA may directly influence brain monoaminergic pathways. When PC12 cells were transiently transfected with plasmids having a luciferase reporter gene under the control of the TH promoter, PPA was found to induce reporter gene activity over a wide concentration range. CREB transcription factor(s) was necessary for the transcriptional activation of TH gene by PPA. At lower concentrations PPA also caused accumulation of TH mRNA and protein, indicative of increased cell capacity to produce catecholamines. PPA and BA induced broad alterations in gene expression including neurotransmitter systems, neuronal cell adhesion molecules, inflammation, oxidative stress, lipid metabolism and mitochondrial function, all of which have been implicated in ASD. In conclusion, our data are consistent with a molecular mechanism through which gut related environmental signals such as

  5. Amino acids 16-275 of minute virus of mice NS1 include a domain that specifically binds (ACCA)2-3-containing DNA.

    PubMed

    Mouw, M; Pintel, D J

    1998-11-10

    GST-NS1 purified from Escherichia coli and insect cells binds double-strand DNA in an (ACCA)2-3-dependent fashion under similar ionic conditions, independent of the presence of anti-NS1 antisera or exogenously supplied ATP and interacts with single-strand DNA and RNA in a sequence-independent manner. An amino-terminal domain (amino acids 1-275) of NS1 [GST-NS1(1-275)], representing 41% of the full-length NS1 molecule, includes a domain that binds double-strand DNA in a sequence-specific manner at levels comparable to full-length GST-NS1, as well as single-strand DNA and RNA in a sequence-independent manner. The deletion of 15 additional amino-terminal amino acids yielded a molecule [GST-NS1(1-275)] that maintained (ACCA)2-3-specific double-strand DNA binding; however, this molecule was more sensitive to increasing ionic conditions than full-length GST-NS1 and GST-NS1(1-275) and could not be demonstrated to bind single-strand nucleic acids. A quantitative filter binding assay showed that E. coli- and baculovirus-expressed GST-NS1 and E. coli GST-NS1(1-275) specifically bound double-strand DNA with similar equilibrium kinetics [as measured by their apparent equilibrium DNA binding constants (KD)], whereas GST-NS1(16-275) bound 4- to 8-fold less well.

  6. Amide Link Scission in the Polyamide Active Layers of Thin-Film Composite Membranes upon Exposure to Free Chlorine: Kinetics and Mechanisms.

    PubMed

    Powell, Joshua; Luh, Jeanne; Coronell, Orlando

    2015-10-20

    The volume-averaged amide link scission in the aromatic polyamide active layer of a reverse osmosis membrane upon exposure to free chlorine was quantified at a variety of free chlorine exposure times, concentrations, and pH and rinsing conditions. The results showed that (i) hydroxyl ions are needed for scission to occur, (ii) hydroxide-induced amide link scission is a strong function of exposure to hypochlorous acid, (iii) the ratio between amide links broken and chlorine atoms taken up increased with the chlorination pH and reached a maximum of ∼25%, (iv) polyamide disintegration occurs when high free chlorine concentrations, alkaline conditions, and high exposure times are combined, (v) amide link scission promotes further chlorine uptake, and (vi) scission at the membrane surface is unrepresentative of volume-averaged scission in the active layer. Our observations are consistent with previously proposed mechanisms describing amide link scission as a result of the hydrolysis of the N-chlorinated amidic N-C bond due to nucleophilic attack by hydroxyl ions. This study increases the understanding of the physicochemical changes that could occur for membranes in treatment plants using chlorine as an upstream disinfectant and the extent and rate at which those changes would occur. PMID:26394532

  7. Amide Link Scission in the Polyamide Active Layers of Thin-Film Composite Membranes upon Exposure to Free Chlorine: Kinetics and Mechanisms.

    PubMed

    Powell, Joshua; Luh, Jeanne; Coronell, Orlando

    2015-10-20

    The volume-averaged amide link scission in the aromatic polyamide active layer of a reverse osmosis membrane upon exposure to free chlorine was quantified at a variety of free chlorine exposure times, concentrations, and pH and rinsing conditions. The results showed that (i) hydroxyl ions are needed for scission to occur, (ii) hydroxide-induced amide link scission is a strong function of exposure to hypochlorous acid, (iii) the ratio between amide links broken and chlorine atoms taken up increased with the chlorination pH and reached a maximum of ∼25%, (iv) polyamide disintegration occurs when high free chlorine concentrations, alkaline conditions, and high exposure times are combined, (v) amide link scission promotes further chlorine uptake, and (vi) scission at the membrane surface is unrepresentative of volume-averaged scission in the active layer. Our observations are consistent with previously proposed mechanisms describing amide link scission as a result of the hydrolysis of the N-chlorinated amidic N-C bond due to nucleophilic attack by hydroxyl ions. This study increases the understanding of the physicochemical changes that could occur for membranes in treatment plants using chlorine as an upstream disinfectant and the extent and rate at which those changes would occur.

  8. A new feruloyl amide derivative from the fruits of Tribulus terrestris.

    PubMed

    Zhang, Xiaopo; Wei, Na; Huang, Jian; Tan, Yinfeng; Jin, Dejun

    2012-01-01

    A new feruloyl amide derivative, named tribulusamide C, was isolated from the fruits of Tribulus terrestris. Its structure was determined on the basis of spectroscopic analysis including IR, 1-D-, 2-D-NMR and HR-ESI-MS. The structure of tribulusamide C was characterised by a unit of pyrrolidine-2,5-dione, which distinguished it from other lignanamides previously isolated from the fruits of T. terrestris.

  9. Ni-Catalyzed Dehydrogenative Cross-Coupling: Direct Transformation of Aldehydes to Esters and Amides

    PubMed Central

    Whittaker, Aaron M.; Dong, Vy M.

    2015-01-01

    By exploring a new mode of Ni-catalyzed cross-coupling, we have developed a protocol to transform both aromatic and aliphatic aldehydes into either esters or amides directly. The success of this oxidative coupling depends on the appropriate choice of catalyst and organic oxidant, including the use of either α,α,α-trifluoroacetophenone or excess aldehyde. We present mechanistic data that supports a catalytic cycle involving oxidative addition into the aldehyde C–H bond. PMID:25424967

  10. Nickel-catalyzed dehydrogenative cross-coupling: direct transformation of aldehydes into esters and amides.

    PubMed

    Whittaker, Aaron M; Dong, Vy M

    2015-01-19

    By exploring a new mode of nickel-catalyzed cross-coupling, a method to directly transform both aromatic and aliphatic aldehydes into either esters or amides has been developed. The success of this oxidative coupling depends on the appropriate choice of catalyst and organic oxidant, including the use of either α,α,α-trifluoroacetophenone or excess aldehyde. Mechanistic data that supports a catalytic cycle involving oxidative addition into the aldehyde C-H bond is also presented. PMID:25424967

  11. MICROBIAL DEGRADATION OF SEVEN AMIDES BY SUSPENDED BACTERIAL POPULATIONS

    EPA Science Inventory

    Microbial transformation rate constants were determined for seven amides in natural pond water. A second-order mathematical rate expression served as the model for describing the microbial transformation. Also investigated was the relationship between the infrared spectra and the...

  12. Silver-catalyzed synthesis of amides from amines and aldehydes

    DOEpatents

    Madix, Robert J; Zhou, Ling; Xu, Bingjun; Friend, Cynthia M; Freyschlag, Cassandra G

    2014-11-18

    The invention provides a method for producing amides via the reaction of aldehydes and amines with oxygen adsorbed on a metallic silver or silver alloy catalyst. An exemplary reaction is shown in Scheme 1: (I), (II), (III). ##STR00001##

  13. An update on potato crisps contents of moisture, fat, salt and fatty acids (including trans-fatty acids) with special emphasis on new oils/fats used for frying.

    PubMed

    Gonçalves Albuquerque, Tânia; Sanches-Silva, Ana; Santos, Lèlita; Costa, Helena S

    2012-09-01

    Eighteen brands of potato crisps, frequently consumed, were analyzed to establish their nutritional value in relation to salt, fat and fatty acid (FA) composition. The purpose of the present study was to determine moisture, total fat, salt contents and FA profiles (including trans-FAs), and to identify the oil/fat used for frying of the 18 brands of potato crisps. Our results show that salt content ranged from 0.127 to 2.77 g/100 g and total fat content of potato crisps varied between 20.0 and 42.8 g/100 g. With respect to FAs analysis, palmitic acid (C16:0), oleic acid (C18:1) and linoleic acid (C18:2) were the major FAs found in the analyzed potato crisps. It is clear from our work that nowadays most potato crisps are currently produced using oils with high contents in unsaturated FAs, which can be considered as healthier from a nutritional point of view. Nevertheless, some brands of potato crisps still use palm oil or a blend of palm oil and other fats/oils, which are very rich in saturated FAs.

  14. Amide temperature coefficients in the protein G B1 domain.

    PubMed

    Tomlinson, Jennifer H; Williamson, Mike P

    2012-01-01

    Temperature coefficients have been measured for backbone amide (1)H and (15)N nuclei in the B1 domain of protein G (GB1), using temperatures in the range 283-313 K, and pH values from 2.0 to 9.0. Many nuclei display pH-dependent coefficients, which were fitted to one or two pK(a) values. (1)H coefficients showed the expected behaviour, in that hydrogen-bonded amides have less negative values, but for those amides involved in strong hydrogen bonds in regular secondary structure there is a negative correlation between strength of hydrogen bond and size of temperature coefficient. The best correlation to temperature coefficient is with secondary shift, indicative of a very approximately uniform thermal expansion. The largest pH-dependent changes in coefficient are for amides in loops adjacent to sidechain hydrogen bonds rather than the amides involved directly in hydrogen bonds, indicating that the biggest determinant of the temperature coefficient is temperature-dependent loss of structure, not hydrogen bonding. Amide (15)N coefficients have no clear relationship with structure.

  15. Nutritional assessment of genetically modified rapeseed synthesizing high amounts of mid-chain fatty acids including production responses of growing-finishing pigs.

    PubMed

    Böhme, Hartwig; Rudloff, Eike; Schöne, Friedrich; Schumann, Wolfgang; Hüther, Liane; Flachowsky, Gerhard

    2007-08-01

    The nutritive value of genetically modified myristic acid-rich rapeseed, in which a acyl-thioesterase gene inserted, was studied. Crude nutrients, amino acid and fatty acid profiles as well as mineral and glucosinolate contents were determined and compared with those of the non-transgenic parental cultivar. The concentration of crude nutrients, minerals and amino acids were found to be within the range of natural variance. The myristic and palmitic acid content increased from 0.1 - 11.4% and from 3.6-20%, respectively, at the expense of oleic acid, which decreased from 68.6-42.6% of total fatty acids. The glucosinolate contents increased from 12.4 micromol/g in the parental plant to 19 micromol/g DM in the GM-plant. Full-fat rapeseed of both cultivars was incorporated in pig diets at a level of 15%, and the digestibility and the production efficiency were tested under ad libitum feeding conditions with ten pigs each over the growing finishing period from 32-105 kg BW. The experimental diets did not show significant differences in digestibility and energetic feeding value. However, feed intake and weight gain decreased presumably due to the increasing glucosinolate intake associated with the feeding of transgenic rapeseed. The dietary fatty acids profile influenced the fatty acid profile of body fat. Myristic acid accumulated in back fat and intramuscular fat while the oleic acid content decreased. The increased glucosinolate intake affected the weight of thyroid glands and their iodine concentration.

  16. Ligand-Promoted, Boron-Mediated Chemoselective Carboxylic Acid Aldol Reaction.

    PubMed

    Nagai, Hideoki; Morita, Yuya; Shimizu, Yohei; Kanai, Motomu

    2016-05-01

    The first carboxylic acid selective aldol reaction mediated by boron compounds and a mild organic base (DBU) was developed. Inclusion of electron-withdrawing groups in the amino acid derivative ligands reacted with BH3·SMe2 forms a boron promoter with increased Lewis acidity at the boron atom and facilitated the carboxylic acid selective enolate formation, even in the presence of other carbonyl groups such as amides, esters, ketones, or aliphatic aldehydes. The remarkable ligand effect led to the broad substrate scope including biologically relevant compounds. PMID:27104352

  17. N-alkyl-4-boronopyridinium salts as thermally stable and reusable amide condensation catalysts.

    PubMed

    Maki, Toshikatsu; Ishihara, Kazuaki; Yamamoto, Hisashi

    2005-10-27

    [reaction: see text] N-Alkyl-4-boronopyridinium salts are highly effective and reusable catalysts for the dehydrative amide condensation reaction between equimolar mixtures of carboxylic acids and amines. N-Alkylboronopyridinium salts are thermally stabilized in the order N-alkyl-2-boronopyridinium salt < N-alkyl-3-boronopyridinium salt < N-alkyl-4-boronopyridinium salt. Homogeneous catalysts, such as 4-borono-N-methylpyridinium iodide, are more effective in the presence of ionic liquid and can be recovered by extraction with ionic liquid. In contrast, heterogeneous catalysts, such as polystyrene-bound 4-boronopyridinium salts, are effective even in the absence of ionic liquid and can be recovered by filtration.

  18. Characterization of an amidated form of pancreatic polypeptide from the daddy sculpin (Cottus scorpius).

    PubMed

    Conlon, J M; Schmidt, W E; Gallwitz, B; Falkmer, S; Thim, L

    1986-12-30

    The primary structure of pancreatic polypeptide from the teleostean fish, Cottus scorpius (daddy sculpin) was established as: YPPQPESPGGNASPEDWAKYHAAVRHYVNLITRQRYNH2 The presence of a COOH-terminally alpha-amidated amino acid was established using an HPLC method of general applicability. Although the peptide shows strong homology towards anglerfish pancreatic polypeptide (86%), homology towards porcine peptide YY (PYY) (61%) and porcine neuropeptide Y (NPY) (61%) was greater than towards porcine pancreatic polypeptide (PP) (47%). This result supports suggestions that the gene duplication events which led to PP, NPY and PYY formation took place after the time of divergence of fish and mammals. PMID:3562898

  19. Fibrate-derived N-(methylsulfonyl)amides with antagonistic properties on PPARα.

    PubMed

    Ammazzalorso, Alessandra; D'Angelo, Alessandra; Giancristofaro, Antonella; De Filippis, Barbara; Di Matteo, Mauro; Fantacuzzi, Marialuigia; Giampietro, Letizia; Linciano, Pasquale; Maccallini, Cristina; Amoroso, Rosa

    2012-12-01

    The identification of novel PPAR ligands represents an attractive research to fully understand the complex biological pathways regulated by these receptors. Selective PPAR modulators, inverse agonists and antagonists of three PPAR isoforms could help to clarify biological effects on lipid and glucose homeostasis. Here we describe the identification of a group of N-(methylsulfonyl)amides, derived from PPARα agonist carboxylic acids. Transactivation and FRET assay confirmed an antagonist behaviour on PPARα for some of these compounds, with submicromolar IC(50). A preliminary analysis on selectivity α/γ revealed different profiles of inhibition or activation. PMID:23137448

  20. GLP-1(32-36)amide Pentapeptide Increases Basal Energy Expenditure and Inhibits Weight Gain in Obese Mice.

    PubMed

    Tomas, Eva; Stanojevic, Violeta; McManus, Karen; Khatri, Ashok; Everill, Paul; Bachovchin, William W; Habener, Joel F

    2015-07-01

    The prevalence of obesity-related diabetes is increasing worldwide. Here we report the identification of a pentapeptide, GLP-1(32-36)amide (LVKGRamide), derived from the glucoincretin hormone GLP-1, that increases basal energy expenditure and curtails the development of obesity, insulin resistance, diabetes, and hepatic steatosis in diet-induced obese mice. The pentapeptide inhibited weight gain, reduced fat mass without change in energy intake, and increased basal energy expenditure independent of physical activity. Analyses of tissues from peptide-treated mice reveal increased expression of UCP-1 and UCP-3 in brown adipose tissue and increased UCP-3 and inhibition of acetyl-CoA carboxylase in skeletal muscle, findings consistent with increased fatty acid oxidation and thermogenesis. In palmitate-treated C2C12 skeletal myotubes, GLP-1(32-36)amide activated AMPK and inhibited acetyl-CoA carboxylase, suggesting activation of fat metabolism in response to energy depletion. By mass spectroscopy, the pentapeptide is rapidly formed from GLP-1(9-36)amide, the major form of GLP-1 in the circulation of mice. These findings suggest that the reported insulin-like actions of GLP-1 receptor agonists that occur independently of the GLP-1 receptor might be mediated by the pentapeptide, and the previously reported nonapeptide (FIAWLVKGRamide). We propose that by increasing basal energy expenditure, GLP-1(32-36)amide might be a useful treatment for human obesity and associated metabolic disorders.

  1. Bioactive phenolic amides from Celtis africana.

    PubMed

    Al-Taweel, Areej Mohammad; Perveen, Shagufta; El-Shafae, Azza Muhammed; Fawzy, Ghada Ahmed; Malik, Abdul; Afza, Nighat; Iqbal, Lubna; Latif, Mehreen

    2012-03-05

    Nine compounds have been isolated for the first time from Celtis africana, namely trans-N-coumaroyltyramine (1), trans-N-feruloyltyramine (2), trans-N-caffeoyltyramine (3), lauric acid (4), oleic acid (5), palmitic acid (6), lupeol (7), β-sitosterol (8) and oleanolic acid (9), respectively. Their structures have been elucidated by different spectroscopic techniques. The isolated compounds were screened for their antioxidant, anti-inflammatory and acetylcholinestrease enzyme inhibitory activities. Compounds 1-3 showed significant antioxidant and anti-inflammatory activities and weak to moderate acetylcholinestrease enzyme inhibition activity.

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

    PubMed

    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. PMID:26991132

  3. The oxalic acid: 2-chloroacetamide crystallization: A new revelation

    NASA Astrophysics Data System (ADS)

    Chitra, R.; Choudhury, R. R.; Capet, Frederic; Roussel, Pascal

    2013-02-01

    The OH of COOH can acts as both donor and acceptor of hydrogen bond. OH of COOH as an acceptor was primarily observed in Oxalic acid Amide complexes. In order to further understand the packing in these complexes, oxalic acid was complexed with 2-tricholoroacetamide. This crystallization resulted in the formation of ammonium tetraoxalate dehydrate. A result similar to what was observed in complexation of oxalic acid with amide containing amino acids (asparagine and glutamine). Interestingly in all these cases, the amide bond is broken, to form the ammonium ion when trying to complex with oxalic acid.

  4. A highly acid-resistant novel strain of Lactobacillus johnsonii No. 1088 has antibacterial activity, including that against Helicobacter pylori, and inhibits gastrin-mediated acid production in mice

    PubMed Central

    Aiba, Yuji; Nakano, Yasuhiro; Koga, Yasuhiro; Takahashi, Kenji; Komatsu, Yasuhiko

    2015-01-01

    A novel strain of Lactobacillus johnsonii No. 1088 was isolated from the gastric juice of a healthy Japanese male volunteer, and characterized for its effectiveness in the stomach environment. Lactobacillus johnsonii No. 1088 was found to have the strongest acid resistance among several lactobacilli examined (>10% of cells survived at pH 1.0 after 2 h), and such a high acid resistance property was a specific characteristic of this strain of L. johnsonii. When cultured with various virulent bacteria, L. johnsonii No. 1088 inhibited the growth of Helicobacter pylori,Escherichia coli O-157, Salmonella Typhimurium, and Clostridium difficile, in which case its effectiveness was more potent than that of a type strain of L. johnsonii,JCM2012. In addition to its effect in vitro, L. johnsonii No. 1088 inhibited the growth of H. pylori in human intestinal microbiota-associated mice in both its live and lyophilized forms. Moreover, L. johnsonii No. 1088 suppressed gastric acid secretion in mice via decreasing the number of gastrin-positive cells in the stomach. These results taken together suggest that L. johnsonii No. 1088 is a unique lactobacillus having properties beneficial for supporting H. pylori eradication by triple therapy including the use of a proton pump inhibitor (PPI) and also for prophylaxis of gastroesophageal reflux disease possibly caused after H. pylori eradication as a side effect of PPI. PMID:25771812

  5. A highly acid-resistant novel strain of Lactobacillus johnsonii No. 1088 has antibacterial activity, including that against Helicobacter pylori, and inhibits gastrin-mediated acid production in mice.

    PubMed

    Aiba, Yuji; Nakano, Yasuhiro; Koga, Yasuhiro; Takahashi, Kenji; Komatsu, Yasuhiko

    2015-06-01

    A novel strain of Lactobacillus johnsonii No. 1088 was isolated from the gastric juice of a healthy Japanese male volunteer, and characterized for its effectiveness in the stomach environment. Lactobacillus johnsonii No. 1088 was found to have the strongest acid resistance among several lactobacilli examined (>10% of cells survived at pH 1.0 after 2 h), and such a high acid resistance property was a specific characteristic of this strain of L. johnsonii. When cultured with various virulent bacteria, L. johnsonii No. 1088 inhibited the growth of Helicobacter pylori, Escherichia coli O-157, Salmonella Typhimurium, and Clostridium difficile, in which case its effectiveness was more potent than that of a type strain of L. johnsonii, JCM2012. In addition to its effect in vitro, L. johnsonii No. 1088 inhibited the growth of H. pylori in human intestinal microbiota-associated mice in both its live and lyophilized forms. Moreover, L. johnsonii No. 1088 suppressed gastric acid secretion in mice via decreasing the number of gastrin-positive cells in the stomach. These results taken together suggest that L. johnsonii No. 1088 is a unique lactobacillus having properties beneficial for supporting H. pylori eradication by triple therapy including the use of a proton pump inhibitor (PPI) and also for prophylaxis of gastroesophageal reflux disease possibly caused after H. pylori eradication as a side effect of PPI.

  6. Phenolic Amides Are Potent Inhibitors of De Novo Nucleotide Biosynthesis.

    PubMed

    Pisithkul, Tippapha; Jacobson, Tyler B; O'Brien, Thomas J; Stevenson, David M; Amador-Noguez, Daniel

    2015-09-01

    An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposure leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using (13)C-labeled sugars and [(15)N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. The results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals.

  7. Phenolic Amides Are Potent Inhibitors of De Novo Nucleotide Biosynthesis

    PubMed Central

    Pisithkul, Tippapha; Jacobson, Tyler B.; O'Brien, Thomas J.; Stevenson, David M.

    2015-01-01

    An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposure leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using 13C-labeled sugars and [15N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. The results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals. PMID:26070680

  8. Phenolic Amides Are Potent Inhibitors of De Novo Nucleotide Biosynthesis.

    PubMed

    Pisithkul, Tippapha; Jacobson, Tyler B; O'Brien, Thomas J; Stevenson, David M; Amador-Noguez, Daniel

    2015-09-01

    An outstanding challenge toward efficient production of biofuels and value-added chemicals from plant biomass is the impact that lignocellulose-derived inhibitors have on microbial fermentations. Elucidating the mechanisms that underlie their toxicity is critical for developing strategies to overcome them. Here, using Escherichia coli as a model system, we investigated the metabolic effects and toxicity mechanisms of feruloyl amide and coumaroyl amide, the predominant phenolic compounds in ammonia-pretreated biomass hydrolysates. Using metabolomics, isotope tracers, and biochemical assays, we showed that these two phenolic amides act as potent and fast-acting inhibitors of purine and pyrimidine biosynthetic pathways. Feruloyl or coumaroyl amide exposure leads to (i) a rapid buildup of 5-phosphoribosyl-1-pyrophosphate (PRPP), a key precursor in nucleotide biosynthesis, (ii) a rapid decrease in the levels of pyrimidine biosynthetic intermediates, and (iii) a long-term generalized decrease in nucleotide and deoxynucleotide levels. Tracer experiments using (13)C-labeled sugars and [(15)N]ammonia demonstrated that carbon and nitrogen fluxes into nucleotides and deoxynucleotides are inhibited by these phenolic amides. We found that these effects are mediated via direct inhibition of glutamine amidotransferases that participate in nucleotide biosynthetic pathways. In particular, feruloyl amide is a competitive inhibitor of glutamine PRPP amidotransferase (PurF), which catalyzes the first committed step in de novo purine biosynthesis. Finally, external nucleoside supplementation prevents phenolic amide-mediated growth inhibition by allowing nucleotide biosynthesis via salvage pathways. The results presented here will help in the development of strategies to overcome toxicity of phenolic compounds and facilitate engineering of more efficient microbial producers of biofuels and chemicals. PMID:26070680

  9. Cations bind only weakly to amides in aqueous solutions.

    PubMed

    Okur, Halil I; Kherb, Jaibir; Cremer, Paul S

    2013-04-01

    We investigated salt interactions with butyramide as a simple mimic of cation interactions with protein backbones. The experiments were performed in aqueous metal chloride solutions using two spectroscopic techniques. In the first, which provided information about contact pair formation, the response of the amide I band to the nature and concentration of salt was monitored in bulk aqueous solutions via attenuated total reflection Fourier transform infrared spectroscopy. It was found that molar concentrations of well-hydrated metal cations (Ca(2+), Mg(2+), Li(+)) led to the rise of a peak assigned to metal cation-bound amides (1645 cm(-1)) and a decrease in the peak associated with purely water-bound amides (1620 cm(-1)). In a complementary set of experiments, the effect of cation identity and concentration was investigated at the air/butyramide/water interface via vibrational sum frequency spectroscopy. In these studies, metal ion-amide binding led to the ordering of the adjacent water layer. Such experiments were sensitive to the interfacial partitioning of cations in either a contact pair with the amide or as a solvent separated pair. In both experiments, the ordering of the interactions of the cations was: Ca(2+) > Mg(2+) > Li(+) > Na(+) ≈ K(+). This is a direct cationic Hofmeister series. Even for Ca(2+), however, the apparent equilibrium dissociation constant of the cation with the amide carbonyl oxygen was no tighter than ∼8.5 M. For Na(+) and K(+), no evidence was found for any binding. As such, the interactions of metal cations with amides are far weaker than the analogous binding of weakly hydrated anions.

  10. Study on selective separation of uranium(VI) by new N,N-dialkyl carboxy-amides

    SciTech Connect

    Suzuki, Shinichi; Sugo, Yumi; Kimura, Takaumi; Yaita, Tsuyoshi

    2007-07-01

    The Feasibility study (FS) on commercialized FR cycle systems has been carried out in Japan. In this Feasibility study, 'Advanced Aqueous' reprocessing was designed as a new reprocessing concept to enhance nuclear non-proliferation by recycling U, Pu and minor actinides (MA) with some fission products (FP). The crystallization and U(VI)/TRU(transuranics) co-extraction technique have been selected as candidate technique in the 'Advanced Aqueous' reprocessing. In JAEA, the result of Feasibility study was received and Fast Reactor Cycle Technology Development Project (FaCT) was started. In the nuclear spent fuel reprocessing, FBR spent fuels will coexist with LWR spent fuels for several decades until FBR cycle begins to operate. For the treatment of LWR spent fuels, high decontamination factor for FP was required for U(VI) storage, and solvent extraction technique was selected in the nuclear fuel treatment. In our laboratory, N,N-di-alkyl carboxy-amides have been developed as extractant based on solvent extraction technique for one of a back-up technology of 'Advanced Aqueous' reprocessing in FBR spent fuel treatments. N,N-di-alkyl carboxy-amides were noted as one of the alternative extractant of tri-butylphosphate (TBP) in the field of nuclear fuel reprocessing. Extraction behavior of U(VI) and Pu(IV) with N,N-di-alkyl carboxy-amides was almost similar to those with TBP. N,N-di-alkyl carboxy-amides have some advantages, namely, their complete incinerability (CHON principle) and high stability for hydrolysis and radiolysis. Their main degradation products are carboxylic acids and secondary amines which hardly affect the separation of U(VI) and Pu(IV) from fission products. Further, the synthesis of N,N-di-alkyl carboxy-amides was relatively easy with reaction of carboxylic chloride and secondary amine. The main purpose of this solvent extraction technique using N,N-di-alkyl carboxy-amides is selective separation of Uranium(VI) with branched N,N-di-alkyl carboxy-amides

  11. Synaptic vesicles contain small ribonucleic acids (sRNAs) including transfer RNA fragments (trfRNA) and microRNAs (miRNA)

    PubMed Central

    Li, Huinan; Wu, Cheng; Aramayo, Rodolfo; Sachs, Matthew S.; Harlow, Mark L.

    2015-01-01

    Synaptic vesicles (SVs) are neuronal presynaptic organelles that load and release neurotransmitter at chemical synapses. In addition to classic neurotransmitters, we have found that synaptic vesicles isolated from the electric organ of Torpedo californica, a model cholinergic synapse, contain small ribonucleic acids (sRNAs), primarily the 5′ ends of transfer RNAs (tRNAs) termed tRNA fragments (trfRNAs). To test the evolutionary conservation of SV sRNAs we examined isolated SVs from the mouse central nervous system (CNS). We found abundant levels of sRNAs in mouse SVs, including trfRNAs and micro RNAs (miRNAs) known to be involved in transcriptional and translational regulation. This discovery suggests that, in addition to inducing changes in local dendritic excitability through the release of neurotransmitters, SVs may, through the release of specific trfRNAs and miRNAs, directly regulate local protein synthesis. We believe these findings have broad implications for the study of chemical synaptic transmission. PMID:26446566

  12. Synaptic vesicles contain small ribonucleic acids (sRNAs) including transfer RNA fragments (trfRNA) and microRNAs (miRNA).

    PubMed

    Li, Huinan; Wu, Cheng; Aramayo, Rodolfo; Sachs, Matthew S; Harlow, Mark L

    2015-01-01

    Synaptic vesicles (SVs) are neuronal presynaptic organelles that load and release neurotransmitter at chemical synapses. In addition to classic neurotransmitters, we have found that synaptic vesicles isolated from the electric organ of Torpedo californica, a model cholinergic synapse, contain small ribonucleic acids (sRNAs), primarily the 5' ends of transfer RNAs (tRNAs) termed tRNA fragments (trfRNAs). To test the evolutionary conservation of SV sRNAs we examined isolated SVs from the mouse central nervous system (CNS). We found abundant levels of sRNAs in mouse SVs, including trfRNAs and micro RNAs (miRNAs) known to be involved in transcriptional and translational regulation. This discovery suggests that, in addition to inducing changes in local dendritic excitability through the release of neurotransmitters, SVs may, through the release of specific trfRNAs and miRNAs, directly regulate local protein synthesis. We believe these findings have broad implications for the study of chemical synaptic transmission.

  13. Synaptic vesicles contain small ribonucleic acids (sRNAs) including transfer RNA fragments (trfRNA) and microRNAs (miRNA).

    PubMed

    Li, Huinan; Wu, Cheng; Aramayo, Rodolfo; Sachs, Matthew S; Harlow, Mark L

    2015-01-01

    Synaptic vesicles (SVs) are neuronal presynaptic organelles that load and release neurotransmitter at chemical synapses. In addition to classic neurotransmitters, we have found that synaptic vesicles isolated from the electric organ of Torpedo californica, a model cholinergic synapse, contain small ribonucleic acids (sRNAs), primarily the 5' ends of transfer RNAs (tRNAs) termed tRNA fragments (trfRNAs). To test the evolutionary conservation of SV sRNAs we examined isolated SVs from the mouse central nervous system (CNS). We found abundant levels of sRNAs in mouse SVs, including trfRNAs and micro RNAs (miRNAs) known to be involved in transcriptional and translational regulation. This discovery suggests that, in addition to inducing changes in local dendritic excitability through the release of neurotransmitters, SVs may, through the release of specific trfRNAs and miRNAs, directly regulate local protein synthesis. We believe these findings have broad implications for the study of chemical synaptic transmission. PMID:26446566

  14. Serous tubal intraepithelial carcinoma upregulates markers associated with high-grade serous carcinomas including Rsf-1 (HBXAP), cyclin E and fatty acid synthase.

    PubMed

    Sehdev, Ann Smith; Kurman, Robert J; Kuhn, Elisabetta; Shih, Ie-Ming

    2010-06-01

    Serous tubal intraepithelial carcinoma (STIC) has been proposed as a precursor for many pelvic high-grade serous carcinomas. Our previous analysis of the ovarian cancer genome identified several genes with oncogenic potential that are amplified and/or overexpressed in the majority of high-grade serous carcinomas. Determining whether these genes are upregulated in STICs is important in further elucidating the relationship of STICs to high-grade serous carcinomas and is fundamental in understanding the molecular pathogenesis of high-grade serous carcinomas. In this study, 37 morphologically defined STICs were obtained from 23 patients with stage IIIC/IV high-grade serous carcinomas. Both STICs and the high-grade serous carcinomas were analyzed for expression of Rsf-1 (HBXAP), cyclin E, fatty acid synthase (FASN) and mucin-4. In addition, they were examined for expression of established markers including p53, Ki-67 and p16. We found that diffuse nuclear p53 and p16 immunoreactivity was observed in 27 (75%) of 36 and 18 (55%) of 33 STICs, respectively, whereas an elevated Ki-67 labeling index (>or=10%) was detected in 29 (78%) of 37 STICs. Cyclin E nuclear staining was seen in 24 (77%) of 35 STICs, whereas normal tubal epithelial cells were all negative. Increased Rsf-1 and FASN immunoreactivity occurred in 63%, and 62% of STICs, respectively, compared with adjacent normal-appearing tubal epithelium. Interestingly, only one STIC showed increased mucin-4 immunoreactivity. Carcinomas, when compared with STICs, overexpressed p16, Rsf-1, cyclin E and FASN in a higher proportion of cases. In conclusion, STICs express several markers including Rsf-1, cyclin E and FASN in high-grade serous carcinomas. In contrast, mucin-4 immunoreactivity either did not change or was reduced in most STICs. These results suggest that overexpression of Rsf-1, cyclin E and FASN occurs early in tumor progression.

  15. Dianthosaponins A-F, triterpene saponins, flavonoid glycoside, aromatic amide glucoside and γ-pyrone glucoside from Dianthus japonicus.

    PubMed

    Nakano, Takahiro; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki

    2011-01-01

    From aerial parts of Dianthus japonicus, six new and seven known oleanane-type triterpene saponins were isolated. The structures of the new saponins, named dianthosaponins A-F, were elucidated by means of high resolution mass spectrometry, and extensive inspection of one- and two-dimensional NMR spectroscopic data. A new C-glycosyl flavone, a glycosidic derivative of anthranilic acid amide and a maltol glucoside were also isolated.

  16. Anchor-linked intermediates in peptide amide synthesis are caused by dimeric anchors on the solid supports.

    PubMed

    Flechsler, I; Beck-Sickinger, A G; Stephan, H; Sheppard, R; Jung, G

    1995-01-01

    Cleavage and kinetic studies have been carried out using commercially obtained H-Tyr(tBu)-5-(4'-aminomethyl-3',5'-dimethoxyphenoxy)valeric acid-TentaGelS (H-Tyr(tBu)-4-ADPV-TentaGelS) and H-Tyr (tBu)-4-ADPV-Ala-aminomethyl-resin (H-Tyr(tBu)-4-ADPV-AM-resin) prepared from commercially available resin and loaded with commercially available Fmoc-4-ADPV-OH amide anchor. Cleavage with pure trifluoroacetic acid (TFA) gave the intermediate H-Tyr-4-ADPV-NH2, which was then degraded to H-Tyr-NH2, and cleavage with TFA/dichloromethane (1:9) yielded H-Tyr-4-ADPV-NH2 which could be isolated in preparative amounts. Cleavage reactions with 15N-labelled H-Ala-4-ADPV-(15N)-Gly-AM-resin yielded the intermediate H-Ala-4-ADPV-NH2, which contained no 15N as demonstrated by 1H-NMR. The analysis of the commercial Fmoc-4-ADPV-OH amide anchor showed the presence of Fmoc-4-ADPV-4-ADPV-OH as an impurity in high amounts. This dimeric anchor molecule is the cause of formation of the anchor-linked peptide intermediate obtained during the cleavage from the resin. The particularly high acid-lability of the amide bond between the two ADPV moieties was utilized to synthesize sidechain and C-terminally 4-ADPV protected pentagastrin on a double-anchor resin, and to cleave it using 5% trifluoroacetic acid in dichloromethane. This method may offer a new way for the synthesis of protected peptide amides with improved solubility to be used in fragment condensation.

  17. A practical synthesis of a high-loading solid-supported IBX amide for the oxidation of alcohols.

    PubMed

    Lecarpentier, Patrick; Crosignani, Stefano; Linclau, Bruno

    2005-01-01

    A straightforward three-step synthesis of a solid-supported IBX amide resin was achieved using inexpensive and commercially available 2-iodobenzoic acid chloride and Merrifield resin. A high apparent loading of 0.63 mmol g(-1) was obtained. Oxidation of a range of alcohols to the corresponding carbonyl compounds proved very straightforward using 1.2 equiv of the resin. Recycling of the resin was also possible with minimal loss of activity after two reoxidations.

  18. Unusual reaction behavior of gem-difluorocyclopropane derivatives: stereoselective synthesis of β-monofluoroallylic alcohols, ethers, esters, and amide.

    PubMed

    Nihei, Takashi; Hoshino, Tomoko; Konno, Tsutomu

    2014-08-15

    On treating gem-difluorocyclopropylstannanes, derived from the radical hydrostannation of gem-difluorocyclopropenes, with 1.5 equiv of MeLi in THF at -78 °C for 5 min, followed by quenching the reaction with various agents, such as H2O, alcohols, carboxylic acids, and tosylamide, the corresponding β-fluoroallylic alcohols, ethers, esters, and amide were obtained with exclusive Z-selectivity in acceptable yields.

  19. Palladium-Catalyzed Carbonylation of β-Arylethylamide Directed by Oxalyl Amide in the Presence of Carbon Monoxide.

    PubMed

    Zhang, Li; Wang, Chao; Han, Jian; Huang, Zhi-Bin; Zhao, Yingsheng

    2016-06-17

    Pd-catalyzed regioselective coupling of β-C(sp(2))-H bonds in aromatic amines protected by oxalyl amide with carbon monoxide is reported. The reaction could tolerate various functional groups and could afford good to excellent yields of the corresponding 3,4-dihydroisoquinolinone derivatives. Remarkably, it could also tolerate β-arylethylamino acid and thiopheneethylamine derivatives, thus showing their potential for producing several important units for bioactive compound synthesis. PMID:27213988

  20. Acetic acid-catalyzed formation of N-phenylphthalimide from phthalanilic acid: a computational study of the mechanism.

    PubMed

    Takahashi, Ohgi; Kirikoshi, Ryota; Manabe, Noriyoshi

    2015-05-28

    In glacial acetic acid, phthalanilic acid and its monosubstituents are known to be converted to the corresponding phthalimides in relatively good yields. In this study, we computationally investigated the experimentally proposed two-step (addition-elimination or cyclization-dehydration) mechanism at the second-order Møller-Plesset perturbation (MP2) level of theory for the unsubstituted phthalanilic acid, with an explicit acetic acid molecule included in the calculations. In the first step, a gem-diol tetrahedral intermediate is formed by the nucleophilic attack of the amide nitrogen. The second step is dehydration of the intermediate to give N-phenylphthalimide. In agreement with experimental findings, the second step has been shown to be rate-determining. Most importantly, both of the steps are catalyzed by an acetic acid molecule, which acts both as proton donor and acceptor. The present findings, along with those from our previous studies, suggest that acetic acid and other carboxylic acids (in their undissociated forms) can catalyze intramolecular nucleophilic attacks by amide nitrogens and breakdown of the resulting tetrahedral intermediates, acting simultaneously as proton donor and acceptor. In other words, double proton transfers involving a carboxylic acid molecule can be part of an extensive bond reorganization process from cyclic hydrogen-bonded complexes.

  1. Asparagine: an amide of particular distinction in the regulation of symbiotic nitrogen fixation of legumes.

    PubMed

    Sulieman, Saad; Tran, Lam-Son Phan

    2013-09-01

    Symbiotic nitrogen fixation is tightly regulated by a range of fine processes at the nodule level, over which the host plant has overall control through the whole life of the plant. The operation of this control at the nodule level is not yet fully understood, but greater knowledge will ultimately lead to a better improvement of N2 fixation through the use of crop legumes and genetic engineering of crop plants for higher performance. It has been suggested that, nodule responses to the nutritional complexity of the rhizosphere environment involve a great deal of coordination of sensing and signal transduction. This regulation can be achieved through several mechanisms, including changes in carbon metabolism, oxygen supply and/or overproduction of reactive oxygen and nitrogen species. Recently, the cycling of amino acids observed between the plant and bacteroid fractions suggests a new and important regulatory mechanism involved in nodule responses. Most of the recent transcriptional findings are consistent with the earlier biochemical and physiological reports. Current research revealed unique advances for nodule metabolism, especially on the regulation of asparagine synthetase gene expression and the control of asparagine (ASN) to N2 fixing activity. A large amount of ASN is found accumulating in the root nodules of the symbiotic plants under restricted environments, such as drought, salinity and nutrient deficiency. Exceptionally, ASN phloem feeding has resulted in an increased concentration of the ASN amide in nodules followed by a remarkable decrease in nodule activity. In this review, recent progress concerning the possible role of ASN in whole-plant-based down-regulation of symbiotic N2 fixation will be reviewed.

  2. Metabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: An analysis of data from the National Health and Nutrition Examination Survey indicated that in older adults exposed to folic acid fortification, the combination of low serum vitamin B-12 and elevated folate is associated with higher concentrations of homocysteine and methylmalonic acid ...

  3. Discovery of amide (peptide) bond synthetic activity in Acyl-CoA synthetase.

    PubMed

    Abe, Tomoko; Hashimoto, Yoshiteru; Hosaka, Hideaki; Tomita-Yokotani, Kaori; Kobayashi, Michihiko

    2008-04-25

    Acyl-CoA synthetase, which is one of the acid-thiol ligases (EC 6.2.1), plays key roles in metabolic and regulatory processes. This enzyme forms a carbon-sulfur bond in the presence of ATP and Mg(2+), yielding acyl-CoA thioesters from the corresponding free acids and CoA. This enzyme belongs to the superfamily of adenylate-forming enzymes, whose three-dimensional structures are analogous to one another. We here discovered a new reaction while studying the short-chain acyl-CoA synthetase that we recently reported (Hashimoto, Y., Hosaka, H., Oinuma, K., Goda, M., Higashibata, H., and Kobayashi, M. (2005) J. Biol. Chem. 280, 8660-8667). When l-cysteine was used as a substrate instead of CoA, N-acyl-l-cysteine was surprisingly detected as a reaction product. This finding demonstrated that the enzyme formed a carbon-nitrogen bond (EC 6.3.1 acid-ammonia (or amide) ligase (amide synthase); EC 6.3.2 acid-amino acid ligase (peptide synthase)) comprising the amino group of the cysteine and the carboxyl group of the acid. N-Acyl-d-cysteine, N-acyl-dl-homocysteine, and N-acyl-l-cysteine methyl ester were also synthesized from the corresponding cysteine analog substrates by the enzyme. Furthermore, this unexpected enzyme activity was also observed for acetyl-CoA synthetase and firefly luciferase, indicating the generality of the new reaction in the superfamily of adenylate-forming enzymes.

  4. Experimental and theoretical understanding of the gas phase oxidation of atmospheric amides with OH radicals: kinetics, products, and mechanisms.

    PubMed

    Borduas, Nadine; da Silva, Gabriel; Murphy, Jennifer G; Abbatt, Jonathan P D

    2015-05-14

    Atmospheric amides have primary and secondary sources and are present in ambient air at low pptv levels. To better assess the fate of amides in the atmosphere, the room temperature (298 ± 3 K) rate coefficients of five different amides with OH radicals were determined in a 1 m(3) smog chamber using online proton-transfer-reaction mass spectrometry (PTR-MS). Formamide, the simplest amide, has a rate coefficient of (4.44 ± 0.46) × 10(-12) cm(3) molec(-1) s(-1) against OH, translating to an atmospheric lifetime of ∼1 day. N-methylformamide, N-methylacetamide and propanamide, alkyl versions of formamide, have rate coefficients of (10.1 ± 0.6) × 10(-12), (5.42 ± 0.19) × 10(-12), and (1.78 ± 0.43) × 10(-12) cm(3) molec(-1) s(-1), respectively. Acetamide was also investigated, but due to its slow oxidation kinetics, we report a range of (0.4-1.1) × 10(-12) cm(3) molec(-1) s(-1) for its rate coefficient with OH radicals. Oxidation products were monitored and quantified and their time traces were fitted using a simple kinetic box model. To further probe the mechanism, ab initio calculations are used to identify the initial radical products of the amide reactions with OH. Our results indicate that N-H abstractions are negligible in all cases, in contrast to what is predicted by structure-activity relationships. Instead, the reactions proceed via C-H abstraction from alkyl groups and from formyl C(O)-H bonds when available. The latter process leads to radicals that can readily react with O2 to form isocyanates, explaining the detection of toxic compounds such as isocyanic acid (HNCO) and methyl isocyanate (CH3NCO). These contaminants of significant interest are primary oxidation products in the photochemical oxidation of formamide and N-methylformamide, respectively.

  5. Anticholesterolemic effect of 3,4-di(OH)-phenylpropionic amides in high-cholesterol fed rats

    SciTech Connect

    Kim, Soon-Ja; Bok, Song-Hae; Lee, Sangku; Kim, Hye-Jin; Lee, Mi-Kyung; Park, Yong Bok; Choi, Myung-Sook . E-mail: mschoi@knu.ac.kr

    2005-10-01

    Two amide synthetic derivatives of 3,4-di(OH)-hydrocinnamate (HC), 3,4-dihydroxyphenylpropionic (L-serine methyl ester) amide (E030) and 3,4-dihydroxyphenylpropionic (L-aspartic acid) amide (E076), were investigated to compare their lipid-lowering efficacy with HC. Male rats were fed a 1 g/100 g high-cholesterol diet for 6 weeks with supplements of either clofibrate (0.02%, w/w), HC (0.025%, w/w), E030 (0.039%, w/w) or E076 (0.041%, w/w). The clofibrate supplement was used as a positive control for the lipid-lowering efficacy. The food intakes and body weight gains were not significantly different among the groups. The plasma and hepatic cholesterol and triglyceride levels were lower in clofibrate, HC, E030, and E076-supplemented groups compared to the control group. The supplementation of HC and its amide derivatives was as effective as clofibrate in increasing the ratio of HDL-cholesterol to total plasma cholesterol and reducing the atherogenic index (AI). The hepatic cholesterol level in the HC and E076 groups was significantly lower than that in the clofibrate group. The hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA reductase) and acyl-CoA:cholesterol acyltransferase (ACAT) activities were significantly lower in the all test groups than in the control group. The excretion of neutral sterol was significantly higher in the HC, E030, and E076-supplemented groups compared to the control group. The plasma AST and ALT activities, indirect indexes of hepatic toxicity, were significantly lower in the HC, E030, and E076-supplemented groups than in the control group. Accordingly, the current results suggest that E030 and E076, two amide synthetic derivatives of HC, are effective in lowering lipid activity.

  6. Modulations in restricted amide rotation by steric induced conformational trapping

    NASA Astrophysics Data System (ADS)

    Krishnan, V. V.; Thompson, William B.; Goto, Joy J.; Maitra, Kalyani; Maitra, Santanu

    2012-01-01

    The rotation around the amide bond in N,N-diethyl-m-toluamide (m-DEET) has been studied extensively and often used in laboratory instructions to demonstrate the phenomenon of chemical exchange. Herein, we show that a simple modification to N,N-diethyl-o-toluamide (o-DEET) significantly alters the dynamics of the restricted rotation around the amide bond due to steric interactions between the ring methyl group and the two N-ethyl groups. This alters the classic two-site exchange due to restricted rotation around the amide bond, to a three-site exchange, with the third conformation trapped at a higher-energy state compared to the other two. This often overlooked phenomenon is elucidated using variable-temperature NMR, two-dimensional exchange spectroscopy and molecular modeling studies.

  7. Nickel-catalysed Suzuki-Miyaura coupling of amides

    NASA Astrophysics Data System (ADS)

    Weires, Nicholas A.; Baker, Emma L.; Garg, Neil K.

    2016-01-01

    The Suzuki-Miyaura coupling has become one of the most important and prevalent methods for the construction of C-C bonds. Although palladium catalysis has historically dominated the field, the use of nickel catalysis has become increasingly widespread because of its unique ability to cleave carbon-heteroatom bonds that are unreactive towards other transition metals. We report the first nickel-catalysed Suzuki-Miyaura coupling of amides, which proceeds by an uncommon cleavage of the amide C-N bond after N-tert-butoxycarbonyl activation. The methodology is mild, functional-group tolerant and can be strategically employed in sequential transition-metal-catalysed cross-coupling sequences to unite heterocyclic fragments. These studies demonstrate that amides, despite classically considered inert substrates, can be harnessed as synthons for use in reactions that form C-C bonds through cleavage of the C-N bond using non-precious metal catalysis.

  8. On the unconventional amide I band in acetanilide

    NASA Astrophysics Data System (ADS)

    Tenenbaum, Alexander; Campa, Alessandro; Giansanti, Andrea

    1987-04-01

    We developed a new model to study the molecular dynamics of the acetanilide (ACN) crystal by computer simulation. Low-frequency oscillations of the molecules as a whole were considered with high-frequency vibrations of the amidic degrees of freedom involved in hydrogen bonding. The low-temperature power spectrum has two peaks, shifted by 15 cm -1, in the region of the amide I band: one of them corresponds to the so-called anomalous amide I band in the IR and Raman spectra of ACN. We found that this peak is due to the coupling of the low-frequency motion in the chain of molecules with the motion of the hydrogen-bonded protons, at variance with current suggestions.

  9. Intramolecular amide bonds stabilize pili on the surface of bacilli

    SciTech Connect

    Budzik, Jonathan M.; Poor, Catherine B.; Faull, Kym F.; Whitelegge, Julian P.; He, Chuan; Schneewind, Olaf

    2010-01-12

    Gram-positive bacteria elaborate pili and do so without the participation of folding chaperones or disulfide bond catalysts. Sortases, enzymes that cut pilin precursors, form covalent bonds that link pilin subunits and assemble pili on the bacterial surface. We determined the x-ray structure of BcpA, the major pilin subunit of Bacillus cereus. The BcpA precursor encompasses 2 Ig folds (CNA{sub 2} and CNA{sub 3}) and one jelly-roll domain (XNA) each of which synthesizes a single intramolecular amide bond. A fourth amide bond, derived from the Ig fold of CNA{sub 1}, is formed only after pilin subunits have been incorporated into pili. We report that the domains of pilin precursors have evolved to synthesize a discrete sequence of intramolecular amide bonds, thereby conferring structural stability and protease resistance to pili.

  10. The contamination mechanism and behavior of amide bond containing organic contaminant on PEMFC

    SciTech Connect

    Cho, Hyun -Seok; Das, Mayukhee; Wang, Heli; Dinh, Huyen N.; Van Zee, J. W.

    2015-02-03

    In this paper, a study is presented of the effects of an organic contaminant containing an amide bond (-CONH-), ε-caprolactam, on polymer electrolyte membrane fuel cells (PEMFCs). The ε-caprolactam has been detected in leachates from polyphthalamide materials that are being considered for use as balance-of-plant structural materials for PEMFCs. Contamination effects from ε-caprolactam in Nafion membranes are shown to be controlled by temperature. A possible explanation of the temperature effect is the endothermic ring-opening reaction of the amide bond (-NHCO-) of the cyclic ε-caprolactam. UV-vis and ATR-IR spectroscopy studies confirmed the presence of open ring structure of ε-caprolactam in membranes. The ECSA and kinetic current for the ORR of the Pt/C catalyst were also investigated and were observed to decrease upon contamination by the ε-caprolactam. By comparison of the CVs of ammonia and acetic acid, we confirmed the adsorption of carboxylic acid (-COOH) or carboxylate anion (-COO-) onto the surface of the Pt. In conclusion, a comparison of in situ voltage losses at 80°C and 50°C also revealed temperature effects, especially in the membrane, as a result of the dramatic increase in the HFR.

  11. Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate.

    PubMed

    Salmeen, Annette; Andersen, Jannik N; Myers, Michael P; Meng, Tzu-Ching; Hinks, John A; Tonks, Nicholas K; Barford, David

    2003-06-12

    The second messenger hydrogen peroxide is required for optimal activation of numerous signal transduction pathways, particularly those mediated by protein tyrosine kinases. One mechanism by which hydrogen peroxide regulates cellular processes is the transient inhibition of protein tyrosine phosphatases through the reversible oxidization of their catalytic cysteine, which suppresses protein dephosphorylation. Here we describe a structural analysis of the redox-dependent regulation of protein tyrosine phosphatase 1B (PTP1B), which is reversibly inhibited by oxidation after cells are stimulated with insulin and epidermal growth factor. The sulphenic acid intermediate produced in response to PTP1B oxidation is rapidly converted into a previously unknown sulphenyl-amide species, in which the sulphur atom of the catalytic cysteine is covalently linked to the main chain nitrogen of an adjacent residue. Oxidation of PTP1B to the sulphenyl-amide form is accompanied by large conformational changes in the catalytic site that inhibit substrate binding. We propose that this unusual protein modification both protects the active-site cysteine residue of PTP1B from irreversible oxidation to sulphonic acid and permits redox regulation of the enzyme by promoting its reversible reduction by thiols.

  12. The contamination mechanism and behavior of amide bond containing organic contaminant on PEMFC

    DOE PAGES

    Cho, Hyun -Seok; Das, Mayukhee; Wang, Heli; Dinh, Huyen N.; Van Zee, J. W.

    2015-02-03

    In this paper, a study is presented of the effects of an organic contaminant containing an amide bond (-CONH-), ε-caprolactam, on polymer electrolyte membrane fuel cells (PEMFCs). The ε-caprolactam has been detected in leachates from polyphthalamide materials that are being considered for use as balance-of-plant structural materials for PEMFCs. Contamination effects from ε-caprolactam in Nafion membranes are shown to be controlled by temperature. A possible explanation of the temperature effect is the endothermic ring-opening reaction of the amide bond (-NHCO-) of the cyclic ε-caprolactam. UV-vis and ATR-IR spectroscopy studies confirmed the presence of open ring structure of ε-caprolactam in membranes.more » The ECSA and kinetic current for the ORR of the Pt/C catalyst were also investigated and were observed to decrease upon contamination by the ε-caprolactam. By comparison of the CVs of ammonia and acetic acid, we confirmed the adsorption of carboxylic acid (-COOH) or carboxylate anion (-COO-) onto the surface of the Pt. In conclusion, a comparison of in situ voltage losses at 80°C and 50°C also revealed temperature effects, especially in the membrane, as a result of the dramatic increase in the HFR.« less

  13. Ferric Hydrogensulfate [Fe(HSO4)3] As a Reusable Heterogeneous Catalyst for the Synthesis of 5-Substituted-1H-Tetrazoles and Amides

    PubMed Central

    Eshghi, Hossein; Seyedi, Seyed Mohammad; Zarei, Elaheh Rahimi

    2011-01-01

    Ferric hydrogensulfate catalyzed the synthesis of 5-substituted 1H-tetrazoles via [2 + 3] cycloaddition of nitriles and sodium azide. This method has the advantages of high yields, simple methodology, and easy workup. The catalyst can be recovered by simple filtration and reused delivering good yields. Also, ferric hydrogensulfate catalyzed the hydrolysis of nitriles to primary amides under aqueous conditions. Various aliphatic and aromatic nitriles converted to the corresponding amides in good yields without any contamination with carboxylic acids. PMID:24052817

  14. A Direct and Stereoretentive Synthesis of Amides from Cyclic Alcohols

    PubMed Central

    Mondal, Deboprosad; Bellucci, Luca

    2013-01-01

    Chlorosulfites prepared in situ using thionyl chloride react with nitrile complexes of titanium (IV) fluoride to give a one-pot conversion of alcohols into amides. For the first time, amides are obtained from cyclic alcohols with stereoretention. Critical to the design of these new Ti(IV) reactions has been the use of little explored Ti(IV) nitrile complexes which are thought to chelate chlorosulfites in the transition state to create a carbocation that is rapidly captured by the nitrile nucleophile via a front-side attack mechanism. PMID:24273447

  15. Copper-Catalyzed Carbonylative Coupling of Cycloalkanes and Amides.

    PubMed

    Li, Yahui; Dong, Kaiwu; Zhu, Fengxiang; Wang, Zechao; Wu, Xiao-Feng

    2016-06-13

    Carbonylation reactions are a most powerful method for the synthesis of carbonyl-containing compounds. However, most known carbonylation procedures still require noble-metal catalysts and the use of activated compounds and good nucleophiles as substrates. Herein, we developed a copper-catalyzed carbonylative transformation of cycloalkanes and amides. Imides were prepared in good yields by carbonylation of a C(sp(3) )-H bond of the cycloalkane with the amides acting as weak nucleophiles. Notably, this is the first report of copper-catalyzed carbonylative C-H activation. PMID:27167881

  16. The temperature dependent amide I band of crystalline acetanilide

    NASA Astrophysics Data System (ADS)

    Cruzeiro, Leonor; Freedman, Holly

    2013-10-01

    The temperature dependent anomalous peak in the amide I band of crystalline acetanilide is thought to be due to self-trapped states. On the contrary, according to the present model, the anomalous peak comes from the fraction of ACN molecules strongly hydrogen-bonded to a neighboring ACN molecule, and its intensity decreases because, on average, this fraction decreases as temperature increases. This model provides, for the first time, an integrated and theoretically consistent view of the temperature dependence of the full amide I band and a qualitative explanation of some of the features of nonlinear pump-probe experiments.

  17. Identification of the growth hormone-releasing hormone analogue [Pro1, Val14]-hGHRH with an incomplete C-term amidation in a confiscated product.

    PubMed

    Esposito, Simone; Deventer, Koen; Van Eenoo, Peter

    2014-01-01

    In this work, a modified version of the 44 amino acid human growth hormone-releasing hormone (hGHRH(1-44)) containing an N-terminal proline extension, a valine residue in position 14, and a C-terminus amidation (sequence: PYADAIFTNSYRKVVLGQLSARKLLQDIMSRQQGESNQERGARARL-NH2 ) has been identified in a confiscated product by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Investigation of the product suggests also an incomplete C-term amidation. Similarly to other hGHRH analogues, available in black markets, this peptide can potentially be used as performance-enhancing drug due to its growth hormone releasing activity and therefore it should be considered as a prohibited substance in sport. Additionally, the presence of partially amidated molecule reveals the poor pharmaceutical quality of the preparation, an aspect which represents a big concern for public health as well.

  18. N-Acylsaccharins: Stable Electrophilic Amide-Based Acyl Transfer Reagents in Pd-Catalyzed Suzuki-Miyaura Coupling via N-C Cleavage.

    PubMed

    Liu, Chengwei; Meng, Guangrong; Liu, Yongmei; Liu, Ruzhang; Lalancette, Roger; Szostak, Roman; Szostak, Michal

    2016-09-01

    The development of efficient catalytic methods for N-C bond cleavage in amides remains an important synthetic challenge. The first Pd-catalyzed Suzuki-Miyaura cross-coupling of N-acylsaccharins with boronic acids by selective N-C bond activation is reported. The reaction enables preparation of a variety of functionalized diaryl and alkyl-aryl ketones with broad functional group tolerance and in good to excellent yields. Of general interest, N-acylsaccharins serve as new, highly reactive, bench-stable, economical, amide-based, electrophilic acyl transfer reagents via acyl-metal intermediates. Mechanistic studies strongly support the amide N-C(O) bond twist as the enabling feature of N-acylsaccharins in the N-C bond cleavage. PMID:27513821

  19. Structural dynamics of soluble chloride intracellular channel protein CLIC1 examined by amide hydrogen-deuterium exchange mass spectrometry.

    PubMed

    Stoychev, Stoyan H; Nathaniel, Christos; Fanucchi, Sylvia; Brock, Melissa; Li, Sheng; Asmus, Kyle; Woods, Virgil L; Dirr, Heini W

    2009-09-01

    Chloride intracellular channel protein 1 (CLIC1) functions as an anion channel in plasma and nuclear membranes when its soluble monomeric form converts to an integral-membrane form. The transmembrane region of CLIC1 is located in its thioredoxin-like domain 1, but the mechanism whereby the protein converts to its membrane conformation has yet to be determined. Since channel formation in membranes is enhanced at low pH (5 to 5.5), a condition that is found at the surface of membranes, the structural dynamics of soluble CLIC1 was studied at pH 7 and at pH 5.5 in the absence of membranes by amide hydrogen-deuterium exchange mass spectrometry (DXMS). Rapid hydrogen exchange data indicate that CLIC1 displays a similar core structure at these pH values. Domain 1 is less stable than the all-helical domain 2, and, while the structure of domain 1 remains intact, its conformational flexibility is further increased in an acidic environment (pH 5.5). In the absence of membrane, an acidic environment appears to prime the solution structure of CLIC1 by destabilizing domain 1 in order to lower the activation energy barrier for its conversion to the membrane-insertion conformation. The significantly enhanced H/D-exchange rates at pH 5.5 displayed by two segments (peptides 11-31 and 68-82) could be due to the protonation of acidic residues in salt bridges. One of these segments (peptide 11-31) includes part of the transmembrane region which, in the solution structure, consists of helix alpha1. This helix is intrinsically stable and is most likely retained in the membrane conformation. Strand beta2, another element of the transmembrane region, displays a propensity to form a helical structure and has putative N- and C-capping motifs, suggesting that it too most likely forms a helix in a lipid bilayer.

  20. Anion transport properties of amine and amide-sidechained peptides are affected by charge and phospholipid composition†

    PubMed Central

    You, Lei; Li, Ruiqiong; Gokel, George W.

    2009-01-01

    Four synthetic anion transporters (SATs) having the general formula (n-C18H37)2N-COCH2OCH2CO-(Gly)3Pro-Lys(ε-N-R)-(Gly)2-O-n-C7H15 were prepared and studied. The group R was Cbz, H (TFA salt), t-Boc, and dansyl in peptides 1, 2, 3, and 4 respectively. The glutamine analog (GGGPQAG sequence) was also included. A dansyl-substituted fluorescent SAT was used to probe peptide insertion; the dansyl sidechain resides in an environment near the bilayer’s midpolar regime. When the lysine sidechain was free or protected amine, little effect was noted on final Cl− transport rate in DOPC : DOPA (7 : 3) liposomes. This stands in contrast to the significant retardation of transport previously observed when a negative glutamate residue was present in the peptide sequence. It was also found that Cl− release from liposomes depended on the phospholipid composition of the vesicles. Chloride transport diminished significantly for the free lysine containing SAT, 2, when the lipid was altered from DOPC : DOPA to pure DOPC. Amide-sidechained SATs 1 and 5 showed a relatively small decrease in Cl− transport. The effect of lipid composition on Cl− transport was explained by differences in electrostatic interaction between amino acid sidechain and lipid headgroup, which was modeled by computation. PMID:18688484