- Singlet oxygen-responsive photorelease of tyramine
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A system capable of photoreleasing tyramine has been developed. The photodonor system consists of an isoindole cage of tyramine and a biscyclometalated Ir(III) complex singlet oxygen (1O2) photosensitizer. Photoirradiation at a wavelength of 365 nm produces tyramine, as evidenced by mass spectrometry and 1H NMR spectroscopy. The photorelease proceeds through two steps involving the formation of a Diels–Alder-type [2 + 4] cycloadduct of 1O2, followed by the slow and spontaneous decomposition of the adduct into tyramine and 2-benzoylbenzophenon.
- Jeong, Dong Yeun,Yi, Seung Yeon,You, Youngmin
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Read Online
- Two-step enzymatic synthesis of tyramine from raw pyruvate fermentation broth
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Tyramine, as a metabolite of tyrosine, is an important intermediate in synthesizing some drugs and medicinal materials. In this study, an efficient method for producing tyramine was developed by a two-step biocatalytic reaction with recombinant tyrosine phenol-lyase whole cells and tyrosine decarboxylase immobilized cells. Raw pyruvate fermentation broth was used as substrate of tyrosine phenol-lyase to economically produce l-tyrosine. l-tyrosine was catalyzed by immobilized tyrosine decarboxylase cells to effectively synthesize tyramine. The conditions of two-step enzymatic catalysis reactions were optimized separately, and the influence of immobilization on tyrosine decarboxylase activity was investigated. In a scale up study, 94.3% l-tyrosine was obtained from raw pyruvate fermentation broth under the optimal conditions. l-Tyrosine was decarboxylated to tyramine with a high yield 91.2%. The total yield of tyramine could reach approximately 86% by this two-step biocatalytic reaction. This study provides us with a green strategy for efficient preparation of tyramine.
- Zhang, Hongjuan,Lu, Yang,Wu, Siping,Wei, Yu,Liu, Qian,Liu, Junzhong,Jiao, Qingcai
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Read Online
- The production of tyramine: Via the selective hydrogenation of 4-hydroxybenzyl cyanide over a carbon-supported palladium catalyst
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The selective production of primary amines is a problem that plagues heterogeneously catalysed nitrile hydrogenation reactions. Whilst the target amine tyramine (HOC6H4CH2CH2NH2) is biochemically available through the action of enzymes, synthetic routes to this species are not widely reported. Here, a heterogeneously catalysed method is proposed that utilises a Pd/C catalyst to effect the selective hydrogenation of 4-hydroxybenzyl cyanide within a three-phase reactor. The aforementioned selectivity issues are overcome by adjustment of various experimental parameters (hydrogen supply, agitation rate, temperature, use of an auxiliary agent) that result in improved catalytic performance, such that the desired tyramine salt (tyramine hydrogen sulphate) can be produced in quantitative yield. Accordingly, through consideration of the interconnectivity of hydrogenation and hydrogenolysis processes, a selective synthetic strategy is achieved with the findings suitable for extension to other substrates of this nature.
- McAllister, Mairi I.,Boulho, Cédric,McMillan, Liam,Gilpin, Lauren F.,Wiedbrauk, Sandra,Brennan, Colin,Lennon, David
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Read Online
- Cytotoxic and α-glucosidase inhibitory metabolites from twigs and leaves of Phyllanthus mirabilis, a species endemic to limestone mountains
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The first investigation of Phyllanthus mirabilis Müll.Arg. led to the isolation of six undescribed compounds including two tyramine derivatives: phyllatyramines A and B; three butenolide analogues, phyllantenolide, phyllantenocoside-O-gallate and epi-phyllantenocoside-O-gallate; and a flavanonol gallate, (?)-taxifolin-3-O-gallate; as well as two first isolated natural products, phyllatyramine C and phyllantenocoside; together with twenty-three known compounds. Their structures were elucidated by spectroscopic means. ECD spectra of all isolated butenolides were compared and assigned the configurations. Phyllatyramine A displayed weak cytotoxicity against the KB cell line, while phyllatyramines B and C showed weak cytotoxicity against KB and HeLa cell lines. In addition, phyllatyramine B and (?)-taxifolin-3-O-gallate showed more potent α-glucosidase inhibitory activity than the standard acarbose 3.4 and 5.8 fold, respectively.
- Chaiyosang, Boonyanoot,Kanokmedhakul, Kwanjai,Kanokmedhakul, Somdej,Laphookhieo, Surat,Phukhatmuen, Piyaporn,Pornpongrungrueng, Pimwadee,Somteds, Apisara,Yahuafai, Jantana
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- AFMT ANALOGS AND THEIR USE IN METHODS OF TREATING PARKINSON'S DISEASE
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The present disclosure provides compounds of formula (I), (II), and (la): Methods of preparing these molecules and their use for treatment of Parkinson's Disease are described.
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Page/Page column 6
(2021/10/30)
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- Multienzyme One-Pot Cascades Incorporating Methyltransferases for the Strategic Diversification of Tetrahydroisoquinoline Alkaloids
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The tetrahydroisoquinoline (THIQ) ring system is present in a large variety of structurally diverse natural products exhibiting a wide range of biological activities. Routes to mimic the biosynthetic pathways to such alkaloids, by building cascade reactions in vitro, represents a successful strategy and can offer better stereoselectivities than traditional synthetic methods. S-Adenosylmethionine (SAM)-dependent methyltransferases are crucial in the biosynthesis and diversification of THIQs; however, their application is often limited in vitro by the high cost of SAM and low substrate scope. In this study, we describe the use of methyltransferases in vitro in multi-enzyme cascades, including for the generation of SAM in situ. Up to seven enzymes were used for the regioselective diversification of natural and non-natural THIQs on an enzymatic preparative scale. Regioselectivites of the methyltransferases were dependent on the group at C-1 and presence of fluorine in the THIQs. An interesting dual activity was also discovered for the catechol methyltransferases used, which were found to be able to regioselectively methylate two different catechols in a single molecule.
- Andexer, Jennifer N.,Cárdenas-Fernández, Max,Hailes, Helen C.,Méndez-Sánchez, Daniel,Richter, Michael,Roddan, Rebecca,Siegrist, Jutta,Subrizi, Fabiana,Thair, Benjamin,Wang, Yu,Ward, John M.
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supporting information
p. 18673 - 18679
(2021/07/19)
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- Enantioselective Sequential-Flow Synthesis of Baclofen Precursor via Asymmetric 1,4-Addition and Chemoselective Hydrogenation on Platinum/Carbon/Calcium Phosphate Composites
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Continuous-flow synthesis of baclofen precursor (2) was achieved using achiral and chiral heterogeneous catalysts in high yield with high enantioselectivity. The key steps are chiral calcium-catalyzed asymmetric 1,4-addition of a malonate to a nitroalkene and chemoselective reduction of a nitro compound to the corresponding amino compound by using molecular hydrogen. A dimethylpolysilane (DMPS)-modified platinum catalyst supported on activated carbon (AC) and calcium phosphate (CP) has been developed that has remarkable activity for the selective hydrogenation of nitro compounds.
- Furiya, Yuichi,Ishitani, Haruro,Kobayashi, Shu
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- Biomimetic synthesis of galantamine: Via laccase/TEMPO mediated oxidative coupling
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Laccase-mediated intramolecular oxidative radical coupling of N-formyl-2-bromo-O-methylnorbelladine afforded a novel and isolable spirocyclohexadienonic intermediate of galantamine. High yield and conversion of substrate were obtained in the presence of the redox mediator 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). This laccase procedure, with an overall yield of 34%, represents a scalable and environmentally friendly alternative to previously reported syntheses of galantamine based on the use of potassium ferricyanide as an unspecific radical coupling reagent.
- Baratto, Maria Camilla,Bizzarri, Bruno Mattia,Botta, Lorenzo,Pogni, Rebecca,Saladino, Raffaele,Zippilli, Claudio
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p. 10897 - 10903
(2020/03/27)
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- Deacetylative Amination of Acetyl Arenes and Alkanes with C-C Bond Cleavage
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The Br?nsted acid-catalyzed synthesis of primary amines from acetyl arenes and alkanes with C-C bond cleavage is described. Although the conversion from an acetyl group to amine has traditionally required multiple steps, the method described herein, which uses an oxime reagent as an amino group source, achieves the transformation directly via domino transoximation/Beckmann rearrangement/Pinner reaction. The method was also applied to the synthesis of γ-aminobutyric acids, such as baclophen and rolipram.
- Hyodo, Kengo,Hasegawa, Genna,Maki, Hiroya,Uchida, Kingo
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supporting information
p. 2818 - 2822
(2019/04/25)
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- Facile in Vitro Biocatalytic Production of Diverse Tryptamines
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Tryptamines are a medicinally important class of small molecules that serve as precursors to more complex, clinically used indole alkaloid natural products. Typically, tryptamine analogues are prepared from indoles through multistep synthetic routes. In the natural world, the desirable tryptamine synthon is produced in a single step by l-tryptophan decarboxylases (TDCs). However, no TDCs are known to combine high activity and substrate promiscuity, which might enable a practical biocatalytic route to tryptamine analogues. We have now identified the TDC from Ruminococcus gnavus as the first highly active and promiscuous member of this enzyme family. RgnTDC performs up to 96 000 turnovers and readily accommodates tryptophan analogues with substituents at the 4, 5, 6, and 7 positions, as well as alternative heterocycles, thus enabling the facile biocatalytic synthesis of >20 tryptamine analogues. We demonstrate the utility of this enzyme in a two-step biocatalytic sequence with an engineered tryptophan synthase to afford an efficient, cost-effective route to tryptamines from commercially available indole starting materials.
- McDonald, Allwin D.,Perkins, Lydia J.,Buller, Andrew R.
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p. 1939 - 1944
(2019/07/08)
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- Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids
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The benzylisoquinoline alkaloids (BIAs) are an important group of secondary metabolites from higher plants and have been reported to show significant biological activities. The production of BIAs through synthetic biology approaches provides a higher-yielding strategy than traditional synthetic methods or isolation from plant material. However, the reconstruction of BIA pathways in microorganisms by combining heterologous enzymes can also give access to BIAs through cascade reactions. Most importantly, non-natural BIAs can be generated through such artificial pathways. In the current study, we describe the use of tyrosinases and decarboxylases and combine these with a transaminase enzyme and norcoclaurine synthase for the efficient synthesis of several BIAs, including six non-natural alkaloids, in cascades from l-tyrosine and analogues.
- Wang, Yu,Tappertzhofen, Nadine,Méndez-Sánchez, Daniel,Bawn, Maria,Lyu, Boyu,Ward, John M.,Hailes, Helen C.
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supporting information
p. 10120 - 10125
(2019/06/27)
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- Organocatalytic Decarboxylation of Amino Acids as a Route to Bio-based Amines and Amides
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Amino acids obtained by fermentation or recovered from protein waste hydrolysates represent an excellent renewable resource for the production of bio-based chemicals. In an attempt to recycle both carbon and nitrogen, we report here on a chemocatalytic, metal-free approach for decarboxylation of amino acids, thereby providing a direct access to primary amines. In the presence of a carbonyl compound the amino acid is temporarily trapped into a Schiff base, from which the elimination of CO2 may proceed more easily. After evaluating different types of aldehydes and ketones on their activity at low catalyst loadings (≤5 mol%), isophorone was identified as powerful organocatalyst under mild conditions. After optimisation many amino acids with a neutral side chain were converted in 28–99 % yield in 2-propanol at 150 °C. When the reaction is performed in DMF, the amine is susceptible to N-formylation. This consecutive reaction is catalysed by the acidity of the amino acid reactant itself. In this way, many amino acids were efficiently transformed to the corresponding formamides in a one-pot catalytic system.
- Claes, Laurens,Janssen, Michiel,De Vos, Dirk E.
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p. 4297 - 4306
(2019/08/26)
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- Rice histone deacetylase 10 and Arabidopsis histone deacetylase 14 genes encode N-acetylserotonin deacetylase, which catalyzes conversion of N-acetylserotonin into serotonin, a reverse reaction for melatonin biosynthesis in plants
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In plants, melatonin production is strictly regulated, unlike the production of its precursor, serotonin, which is highly inducible in response to stimuli, such as senescence and pathogen exposure. Exogenous serotonin treatment does not greatly induce the production of N-acetylserotonin (NAS) and melatonin in plants, which suggests the possible existence of one or more regulatory genes in the pathway for the biosynthesis of melatonin from serotonin. In this report, we found that NAS was rapidly and abundantly converted into serotonin in rice seedlings, indicating the presence of an N-acetylserotonin deacetylase (ASDAC). To clone the putative ASDAC gene, we screened 4 genes that were known as histone deacetylase (HDAC) genes, but encoded proteins targeted into chloroplasts or mitochondria rather than nuclei. Of 4 recombinant Escherichia coli strains expressing these genes, one E.?coli strain expressing the rice HDAC10 gene was found to be capable of producing serotonin in response to treatment with NAS. The recombinant purified rice HDAC10 (OsHDAC10) protein exhibited ASDAC enzyme activity toward NAS, N-acetyltyramine (NAT), N-acetyltryptamine, and melatonin, with the highest ASDAC activity for NAT. In addition, its Arabidopsis ortholog, AtHDAC14, showed similar ASDAC activity to that of OsHDAC10. Both OsHDAC10 and AtHDAC14 were found to be expressed in chloroplasts. Phylogenetic analysis indicated that ASDAC homologs were present in archaea, but not in cyanobacteria, which differs from the distribution of serotonin N-acetyltransferase (SNAT). This suggests that SNAT and ASDAC may have evolved differently from ancestral eukaryotic cells.
- Lee, Kyungjin,Lee, Hyoung Yool,Back, Kyoungwhan
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- Compositions and methods for producing benzylisoquinoline alkaloids
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The present invention relates to host cells that produce compounds that are characterized as benzylisoquinolines, as well as select precursors and intermediates thereof. The host cells comprise one, two or more heterologous coding sequences wherein each of the heterologous coding sequences encodes an enzyme involved in the metabolic pathway of a benzylisoquinoline, or its precursors or intermediates from a starting compound. The invention also relates to methods of producing the benzylisoquinoline, as well as select precursors and intermediates thereof by culturing the host cells under culture conditions that promote expression of the enzymes that produce the benzylisoquinoline or precursors or intermediates thereof.
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Page/Page column 2; 4; 11-12
(2016/05/19)
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- Tyramine compound and preparation method thereof
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The invention discloses a tyramine compound and a preparation method thereof. The preparation method includes the following steps: after phenol and formic acid first react for 2 hours, nitromethane and ammonium acetate are added, compound b can be obtained by reaction after 2 hours of reflux, hydrogen is then injected into the compound b produced in the reaction under the catalysis of TiO2-NiO-Fe mixture, temperature is controlled at 50DEG C to 60DEG C, and after 4 to 5.5 hours of continuous reaction, the target product, tyramine, is obtained. The materials of the method are cheap and easy to obtain, the synthetic route is novel, the cost is low, operation condition requirement is low, and the preparation method is environment-friendly and suitable for mass industrial production.
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Paragraph 0028; 0029; 0030
(2017/04/03)
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- Ezrin inhibitors and methods of making and using
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The invention encompasses compound and pharmaceutical composition comprising the compound of the following Formula (I): or pharmaceutically acceptable salts or prodrugs thereof, that are useful for inhibiting ezrin protein in a cell or for inhibiting the growth of a cancer cell.
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Page/Page column 56
(2017/01/05)
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- PRODUCTION METHOD FOR COMPOUND COMPRISING AMINO GROUP AND/OR HYDROXYL GROUP
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Disclosed is a method for producing a compound having an amino group and/or a hydroxyl group from a substrate compound having an atomic group containing CO or CS by eliminating said atomic group. The substrate compound having an atomic group containing CO or CS (for example, an amide, a carbamate, or the like) is allowed to react with a compound expressed by formula (I) below, at a temperature of 120°C or lower, preferably in the presence of an ammonium salt, to eliminate said atomic group containing CO or CS. In formula (I) A may not be present, and in a case where A is present, A represents an alkyl group having 1 to 6 carbon atoms. ????????H2N-A-NH2?????(I)
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Paragraph 0040-0041; 0046
(2015/01/18)
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- Total synthesis of cannabisin F
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A practical eight-step synthesis of lignanamide cannabisin F starting from vanillin is reported for the first time. This synthetic strategy applies the aldol reaction followed by the Wittig reaction to afford the key 8-O-4′-neolignan intermediate diacid. The diacid was condensed with N,O-protected tyramine giving, after deprotection, cannabisin F.
- Xia, Ya-Mu,Xia, Jun,Chai, Chen
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p. 384 - 391
(2014/01/06)
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- Preparation of functional styrenes from biosourced carboxylic acids by copper catalyzed decarboxylation in PEG
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A general protocol for the copper-catalyzed decarboxylation of α,β-unsaturated carboxylic acids in PEG, particularly of biosourced cinnamic acid analogues, is reported. Moderate to high isolated yields (31-96%) towards the styrene derivatives were obtained. For the first time, decarboxylation of α-amino acids to the corresponding amines was successfully performed with good to high yields and extended to the decarboxylation of a few condensed heterocyclic compounds. Both the use of PEG as a green solvent and direct separation of the pure product of the reaction by distillation permitted the reuse of the solvent and the Cu-based catalytic system over several cycles without deactivation. This was extended to the synthesis of 4-vinylguaiacol on the laboratory scale in an average 92% yield. This journal is the Partner Organisations 2014.
- Cadot, Stephane,Rameau, Nelly,Mangematin, Stephane,Pinel, Catherine,Djakovitch, Laurent
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supporting information
p. 3089 - 3097
(2014/06/10)
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- Investigation of a substrate-specifying residue within Papaver somniferum and Catharanthus roseus aromatic amino acid decarboxylases
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Plant aromatic amino acid decarboxylases (AAADs) catalyze the decarboxylation of aromatic amino acids with either benzene or indole rings. Because the substrate selectivity of AAADs is intimately related to their physiological functions, primary sequence data and their differentiation could provide significant physiological insights. However, due to general high sequence identity, plant AAAD substrate specificities have been difficult to identify through primary sequence comparison. In this study, bioinformatic approaches were utilized to identify several active site residues within plant AAAD enzymes that may impact substrate specificity. Next a Papaver somniferum tyrosine decarboxylase (TyDC) was selected as a model to verify our putative substrate-dictating residues through mutation. Results indicated that mutagenesis of serine 372 to glycine enables the P. somniferum TyDC to use 5-hydroxytryptophan as a substrate, and reduces the enzyme activity toward 3,4-dihydroxy-L-phenylalanine (dopa). Additionally, the reverse mutation in a Catharanthus roseus tryptophan decarboxylase (TDC) enables the mutant enzyme to utilize tyrosine and dopa as substrates with a reduced affinity toward tryptophan. Molecular modeling and molecular docking of the P. somniferum TyDC and the C. roseus TDC enzymes provided a structural basis to explain alterations in substrate specificity. Identification of an active site residue that impacts substrate selectivity produces a primary sequence identifier that may help differentiate the indolic and phenolic substrate specificities of individual plant AAADs.
- Torrens-Spence, Michael P.,Lazear, Michael,Von Guggenberg, Renee,Ding, Haizhen,Li, Jianyong
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- Biochemical evaluation of a parsley tyrosine decarboxylase results in a novel 4-hydroxyphenylacetaldehyde synthase enzyme
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Plant aromatic amino acid decarboxylases (AAADs) are effectively indistinguishable from plant aromatic acetaldehyde syntheses (AASs) through primary sequence comparison. Spectroscopic analyses of several characterized AASs and AAADs were performed to look for absorbance spectral identifiers. Although this limited survey proved inconclusive, the resulting work enabled the reevaluation of several characterized plant AAS and AAAD enzymes. Upon completion, a previously reported parsley AAAD protein was demonstrated to have AAS activity. Substrate specificity tests demonstrate that this novel AAS enzyme has a unique substrate specificity towards tyrosine (km 0.46. mM) and dopa (km 1.40. mM). Metabolite analysis established the abundance of tyrosine and absence of dopa in parsley extracts. Such analysis indicates that tyrosine is likely to be the sole physiological substrate. The resulting information suggests that this gene is responsible for the in vivo production of 4-hydroxyphenylacetaldehyde (4-HPAA). This is the first reported case of an AAS enzyme utilizing tyrosine as a primary substrate and the first report of a single enzyme capable of producing 4-HPAA from tyrosine.
- Torrens-Spence, Michael P.,Gillaspy, Glenda,Zhao, Bingyu,Harich, Kim,White, Robert H.,Li, Jianyong
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experimental part
p. 211 - 216
(2012/07/14)
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- NANOPARTICLE, LIPOSOMES, POLYMERS, AGENTS AND PROTEINS MODIFIED WITH REVERSIBLE LINKERS
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Pharmaceutical, chemical and biological agents containing a reversible disulfide linker are described. These agents can also be covalently bound or contained in delivery vehicles for delivering the agents to desired targets or areas. Also described are delivery vehicles which contain an agent having a reversible disulfide linker and to vehicles that are covalently linked to the agent containing a reversible disulfide linker. The modifications described herein can modify properties of the agents and vehicles, thereby providing desired solubility, stability, hydrophobicity and targeting while the reversibility of the linker can leave the agent to which it is attached free from residual chemical groups after being reduced.
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Page/Page column 81
(2012/09/10)
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- Microwave-assisted deacylation of unactivated amides using ammonium-salt-accelerated transamidation
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Easy does it! The chemoselective oxidative ?-C(sp3)H alkylation/cyclization reaction of N-benzyl carbamates using simple mono-, di-, and trisubstituted olefins provides functionalized N-heterocycles such as oxazinones (see picture). A TEMPO oxoammonium salt serves as the oxidant, making it possible to carry out the reaction at low temperatures. Neither a metal catalyst nor preactivation in the ?-position to the nitrogen group are needed.
- Shimizu, Yuhei,Morimoto, Hiroyuki,Zhang, Ming,Ohshima, Takashi
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supporting information; experimental part
p. 8564 - 8567
(2012/09/11)
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- A high-throughput screening assay for amino acid decarboxylase activity
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The development of sensitive and easy-to-apply high-throughput screening methods is a common need in modern biocatalysis. With these powerful analytical tools in hands, chemists can easily assess enzyme libraries to identify either novel biocatalysts or improved mutants. Within biocatalysis, amino acid decarboxylases are gaining an increased importance, with several diverse applications ranging from the synthesis of bio-commodities to medical applications (e.g., synthesis of enzyme inhibitors at the level of L-DOPA decarboxylase). Herein, an efficient and simple analytical method for high-throughput screening of amino acid decarboxylase activity is reported. The method is valid for the discrimination of a broad range of amino acid/amine pairs such as L-tyrosine/tyramine, L-DOPA/dopamine, 5-hydroxy-L-tryptophan/ serotonin, L-histidine/histamine, L-serine/ethanolamine, L-tryptophan/ tryptamine, L-glutamic acid/GABA, and L-alanine/ethylamine. It has proven its versatility by using pure substrates, mixtures, or enzymatic reactions, both coming either from commercial enzymes or derived from cell-free (crude) extracts. The limit of detection was 13 μM for ethanolamine in the presence of 50 mM L-serine, while z′ values were in the range 0.75-0.93, indicating the suitability for high-throughput screening. Copyright
- Medici, Rosario,De Maria, Pablo Dominguez,Otten, Linda G.,Straathof, Adrie J. J.
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experimental part
p. 2369 - 2376
(2011/10/13)
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- Assessment of enzymatic methods in the δ18O value determination of the l -tyrosine p -hydroxy group for proof of illegal meat and bone meal feeding to cattle
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The δ18O value of the p-hydroxy group of l-tyrosine depends on the biosynthesis by plants or animals, respectively. In animal proteins it reflects the diet and is therefore an absolute indicator for illegal feeding with meat and bone meal. The aim of this investigation was to perform the positional 18O determination on l-tyrosine via a one-step enzymatic degradation. Proteins from plants, herbivores, omnivores, and carnivores were characterized by their δ13C, δ15N, and δ18O values, the latter for normalizing the positional δ18O values. Their l-tyrosine was degraded by tyrosine phenol lyase to phenol, analyzed as (2,4,6)-tribromophenol. Degradation by tyrosine decarboxylase yielded tyramine. The δ18O values of both analytes corresponded to the trophic levels of their sources but were not identical, probably due to an isotope effect on the tyrosine phenol lyase reaction. Availability of the enzyme, easy control of the reaction, and isolation of the analyte are in favor of tyrosine decarboxylase degradation as a routine method.
- Tanz, Nicole,Werner, Roland A.,Eisenreich, Wolfgang,Schmidt, Hanns-Ludwig
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experimental part
p. 9475 - 9483
(2011/12/21)
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- Simple and efficient one-step conversion of benzonitrile into methylarene under mild conditions
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A very simple and efficient method has been developed for the synthesis of various methylarenes from the corresponding benzonitriles under mild conditions. The protocol uses Pearlmans catalyst to achieve the transformation under an atmosphere of gaseous hydrogen and proceeds smoothly in many common solvents. A series of methylarenes were thus obtained in high yields and purities. Georg Thieme Verlag Stuttgart - New York.
- Ouellet, étienne,Poirier, Donald
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experimental part
p. 2025 - 2028
(2011/10/12)
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- Enantiomeric propanolamines as selective N-methyl-D-aspartate 2B receptor antagonists
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Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC50 values between 30-100 nM. Potency is strongly controlled by substitution on both rings and the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity and chain-length factors provide the greatest inhibitory potency. Structural comparisons based on 3D shape analysis and electrostatic complementarity support this conclusion. The antagonists are neuroprotective in both in vitro and in vivo models of ischemic cell death. In addition, some compounds exhibit anticonvulsant properties. Unlike earlier generation NMDA receptor antagonists and some NR2B-selective antagonists, the present series of propanolamines does not cause increased locomotion in rodents. Thus, the NR2B-selective antagonists exhibit a range of therapeutically interesting properties.
- Tahirovic, Yesim A.,Geballe, Matthew,Gruszecka-Kowalik, Ewa,Myers, Scott J.,Lyuboslavsky, Polina,Le, Phuong,French, Adam,Irier, Hasan,Choi, Woo-Baeg,Easterling, Keith,Yuan, Hongjie,Wilson, Lawrence J.,Kotloski, Robert,McNamara, James O.,Dingledine, Raymond,Liotta, Dennis C.,Traynelis, Stephen F.,Snyder, James P.
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supporting information; experimental part
p. 5506 - 5521
(2009/08/07)
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- Tetracyclic benzimidazole derivatives and combinatorial libraries thereof
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The present invention relates to novel tetracyclic benzimidazole derivative compounds of the following formula: wherein R1to R10have the meanings described in here. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing tetracyclic benzimidazole derivative compounds.
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- Self emulsifying drug delivery systems for poorly soluble drugs
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A pharmaceutical composition in a form of a self microemulsifying drug delivery system comprising:one or more therapeutic agent(s) which have low solubility in water or are water-insoluble,vitamin E,one co-solvent selected from propylene glycol and ethanol,one or more bile salts,TPGS, andone further surfactant selected from Tyloxapol and polyoxyl hydrogenated castor oil.
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- LABELLING AND SELECTION OF MOLECULES
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A method of labelling molecules which includes providing in a common medium a label molecule, a marker ligand able to bind a member of a specific binding pair, such as an antigen, a sbp member, an enzyme able to catalyse binding of the label molecule to other molecules, the enzyme being associated with the marker ligand; causing or allowing binding of the marker ligand to the sbp member; and causing or allowing binding of the label molecule to other molecules in the vicinity of the marker ligand bound to the sbp member. The marker ligand may be an antibody or any specific binding molecule, such as a chemokine or cytokine. A complementary member of the specific binding pair may be included, e.g. an antibody, or a diverse population of such sbp members, e.g. antibodies, may be included within which those which bind the counterpart sbp member, e.g. antigen, may be labelled and subsequently isolated for manipulation and/or use. Suitable labels include biotin-tyramine with signal transfer being catalysed by hydrogen peroxidase. Cells, virus particles and other moieties may be labelled, for identification or obtention of proteins which interact or are in close proximity with a particular sbp member, or of cells of interest, or for enhancement of labelling, e.g. for cell sorting.
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- Derivatives of 1,2-dihydro-7-hydroxyquinolines containing fused rings
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The present invention describes novel dyes, including coumarins, rhodamines, and rhodols that incorporate additional fused aromatic rings. The dyes of the invention absorb at a longer wavelength than structurally similar dyes that do not possess the fused aromatic rings. Many of the dyes of the invention are useful fluorescent dyes. The invention includes chemically reactive dyes, dye-conjugates, and the use of such dyes in staining samples and detecting ligands or other analytes.
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- A photo-sensitive protecting group for amines based on coumarin chemistry
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There is a continuing need for the development of new protecting groups for amines which can be cleaved under conditions that are mild and fundamentally different from what are already available. In this paper, we report our studies in using o-hydroxy-trans-cinnamic acid as a photo- sensitive protecting group for amines. The design takes advantage of the trans-cis photo-isomerization and the ensuing facile lactonization of o- hydroxy-cis-cinnamic acid and derivatives. We have found that both the protection and deprotection can be carried out in high yields for a variety of amines with different structural features. The deprotection reaction uses low intensity UV light (365 nm), which is fundamentally different from the conditions used for the deprotection of other commonly used amino-protecting groups. Therefore, the method complements other available methods in allowing for selective manipulation of different functional groups in a complex organic molecule.
- Wang, Binghe,Zheng, Ailian
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p. 715 - 718
(2007/10/03)
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- Contact lens cleaning composition containing polyalklene oxide modified siloxanes
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Compositions and methods are provided for cleaning and wetting of contact lenses, especially rigid, gas-permeable contact lenses. The compositions comprise low molecular weight polyalkylene oxide modified siloxanes, which are particularly effective in removing lipids from the surface of contact lenses.
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- Reductive Radical Decarboxylation of Amino-acids and Peptides
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Radicals generated from N-protected α-amino-acids by photolysis of their N-hydroxypyridine-2-thione esters at room temperature are efficiently quenched by t-butyl thiol to give decarboxy-acids; comparable reactions have been carried out on the side chain carboxy groups of suitable protected aspartic and glutamic acids.
- Barton, Derek H. R.,Herve, Yolande,Potier, Pierre,Thierry, Josiane
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p. 1298 - 1299
(2007/10/02)
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- Enzyme Amplification for Trace Level Determination of Pyridoxal 5'-Phosphate with a pCO2 Electrode
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A highly sensitive and selective potentiometric method for the determination of the enzymatically active form of vitamin B6, pyridoxal 5'-phosphate (PLP), has been devised.The method is based upon the decarboxylation of L-tyrosine by the apoenzyme tyrosine decarboxylase in the presence of PLP, using a pCO2 electrode to monitor the reaction rate.Under optimized conditions, an amplification factor of up to 1E5 is achieved, and PLP levels as low as 1E-9 M can be measured with good precision and an analysis time of only 20 min.Other members of the vitamin B6 group and their phosphate derivatives do not interfere with the proposed method.
- Hassan, Saad S. M.,Rechnitz, G. A.
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p. 512 - 515
(2007/10/02)
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- Aromatic L-Amino Acid Decarboxylase from Micrococcus percitreus Purification, Crystallization and Properties
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An aromatic L-amino acid decarboxylase was crystallized from the cell free extract of Micrococcus percitreus.The purification procedure included protamine sulfate treatment, ammonium sulfate fractionation, DEAE-Sephadex column chromatography and Sephadex G-200 filtration.Crystals were obtained from a solution of the purified enzyme by addition of ammonium sulfate.The crystalline enzyme preparation was homogeneous as judged by ultracentrifugation and SDS-polyacrylamide gel electrophoresis.The molecular weight was determined to be approximately 101,000.The enzyme was evidently composed of two identical subunits of a molecular weight of 48,000.The enzyme catalyzed the stoichiometric conversion of L-tryptophan to tryptamine and CO2 in the presence of pyridoxal phosphate.The optimum pH was 9.0 for the conversion.The Km value and the maximum velocity of L-tryptophan decarboxylation were 2.4E-3 M and 44 μmol/min/mg of protein, respectively.This enzyme also catalyzed decarboxylation of 5-hydroxy-L-tryptophan, L-phenylalanine, L-tyrosine, 3,4-dihydroxy-L-phenylalanine, L-kynurenine and thier α-methyl amino acid derivatives.
- Nakazawa, Hidetsugu,Kumagai, Hidehiko,Yamada, Hideaki
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p. 2543 - 2552
(2007/10/02)
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- Biogenesis of Epidithiadiketopiperazines. Synthesis of Three Isomeric (β-Aminoethyl)benzene Oxides
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Three isomeric amine-substituted arene oxides have been synthesized to serve as models for the postulated involvement of amino acid derived arene oxides during the biosyntheses of various epidithiadiketopiperazines.No biogenetic-type reactivity was noted for the arene oxides.In all three cases aromatization rather than amine/epoxide cyclization was observed.The failure to duplicate the presumed in vivo reactivity of aminoarene oxides is discussed in terms of possible enzyme-mediated cyclizations in the natural systems.
- Rastetter, William H.,Nummy, Larry J.
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p. 3149 - 3155
(2007/10/02)
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- Introduction of the (Dimethylhydrazono)ethyl Group into Methylene Active Compounds and Phenols
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In trimethylammonium iodide the trimethylammonium group can be substituted by several nucleophiles.With this reagent (dimethylhydrazono)ethyl derivatives of CH-acidic compounds, phenols, and indole can be prepared.
- Severin, Theodor,Lerche, Holger,Mayring, Lothar
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p. 970 - 978
(2007/10/02)
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- UN NOUVEL HETEROSIDE NITRE EXTRAIT D'ANNONA SQUAMOSA
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A new glycoside was isolated from a 60percent methanol extract of dried leaves and stems of Annona squamosa.Its chemical structure was determined as 4-(-2-nitroethyl)-1-benzene.Key Word Index -- Annona squamosa; Annonaceae; primeveroside; 4-(-2-nitroethyl)phenol; 4-(-2-aminoethyl)phenol; tyramine.
- Forgacs, P.,Desconclois, J. F.,Provost, J.,Tiberghien, R.,Touche, A.
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p. 1251 - 1252
(2007/10/02)
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- Serotonin receptor affinities of psychoactive phenalkylamine analogues
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Employing a rat fundus model, the serotonin (5-HT) receptor affinities of 45 phenalkylamine analogues were determined. Phenethylamine and phenylisopropylamine possess relatively low receptor affinities; in general, mono-, di-, and trimethoxylation enhance affinity. Of the disubstituted compounds, methoxyl groups at the 2 and 5 positions are optimal for imparting a high affinity. 4-Methylation, 4-ethylation and 4-bromination also enhance receptor affinity, while N,N-dimethylation of the terminal amine decreases affinity. α-Methylation of phenethylamines has little effect on affinity when racemates are examined. Introduction of a benzylic keto group can either increase or decrease affinity, depending upon the presence of other aromatic substituents. The most behaviorally active compounds were found to possess the highest 5-HT receptor affinities, while less active compounds were found to possess lower affinities.
- Glennon,Liebowitz,Anderson III
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p. 294 - 299
(2007/10/02)
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