- Novel Tween 20 derivatives enable the formation of efficient pH-sensitive drug delivery vehicles for human hepatoblastoma
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We describe the synthesis, the physicochemical characterization and the biological evaluation of three novel pH-sensitive systems prepared derivatizing polysorbate 20 (Tween 20) with glycine, N-methyl-glycine and N,N-dimethyl-glycine (TW20-GLY, TW20-MMG and TW20-DMG). These derivatives form pH-sensitive vesicles and translocate small molecules into cells. The reported systems are efficient drug delivery systems for human hepatoblastoma cells.
- Masotti, Andrea,Vicennati, Paola,Alisi, Anna,Marianecci, Carlotta,Rinaldi, Federica,Carafa, Maria,Ortaggi, Giancarlo
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Read Online
- An Anomalous Eschweiler-Clarke Reaction
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Reaction of β-alanine 1 with formaldehyde in the presence of formic acid under Eschweiler-Clarke conditions yields the corresponding betaine 3 instead of the expected N,N-dimethyl β-alanine 2
- Rahal, Said,Badache, Leila
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Read Online
- Electroactivated alkylation of amines with alcohols: Via both direct and indirect borrowing hydrogen mechanisms
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A green, efficient N-alkylation of amines with simple alcohols has been achieved in aqueous solution via an electrochemical version of the so-called "borrowing hydrogen methodology". Catalyzed by Ru on activated carbon cloth (Ru/ACC), the reaction works well with methanol, and with primary and secondary alcohols. Alkylation can be accomplished by either of two different electrocatalytic processes: (1) in an undivided cell, alcohol (present in excess) is oxidized at the Ru/ACC anode; the aldehyde or ketone product condenses with the amine; and the resulting imine is reduced at an ACC cathode, combining with protons released by the oxidation. This process consumes stoichiometric quantities of current. (2) In a membrane-divided cell, the current-activated Ru/ACC cathode effects direct C-H activation of the alcohol; the resulting carbonyl species, either free or still surface-adsorbed, condenses with amine to form imine and is reduced as in (1). These alcohol activation processes can alkylate primary and secondary aliphatic amines, as well as ammonia itself at 25-70 °C and ambient pressure.
- Appiagyei, Benjamin,Bhatia, Souful,Keeney, Gabriela L.,Dolmetsch, Troy,Jackson, James E.
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supporting information
p. 860 - 869
(2020/02/21)
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- A New Microbial Pathway for Organophosphonate Degradation Catalyzed by Two Previously Misannotated Non-Heme-Iron Oxygenases
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The assignment of biochemical functions to hypothetical proteins is challenged by functional diversification within many protein structural superfamilies. This diversification, which is particularly common for metalloenzymes, renders functional annotations that are founded solely on sequence and domain similarities unreliable and often erroneous. Definitive biochemical characterization to delineate functional subgroups within these superfamilies will aid in improving bioinformatic approaches for functional annotation. We describe here the structural and functional characterization of two non-heme-iron oxygenases, TmpA and TmpB, which are encoded by a genomically clustered pair of genes found in more than 350 species of bacteria. TmpA and TmpB are functional homologues of a pair of enzymes (PhnY and PhnZ) that degrade 2-aminoethylphosphonate but instead act on its naturally occurring, quaternary ammonium analogue, 2-(trimethylammonio)ethylphosphonate (TMAEP). TmpA, an iron(II)- and 2-(oxo)glutarate-dependent oxygenase misannotated as a γ-butyrobetaine (γbb) hydroxylase, shows no activity toward γbb but efficiently hydroxylates TMAEP. The product, (R)-1-hydroxy-2-(trimethylammonio)ethylphosphonate [(R)-OH-TMAEP], then serves as the substrate for the second enzyme, TmpB. By contrast to its purported phosphohydrolytic activity, TmpB is an HD-domain oxygenase that uses a mixed-valent diiron cofactor to enact oxidative cleavage of the C-P bond of its substrate, yielding glycine betaine and phosphate. The high specificities of TmpA and TmpB for their N-trimethylated substrates suggest that they have evolved specifically to degrade TMAEP, which was not previously known to be subject to microbial catabolism. This study thus adds to the growing list of known pathways through which microbes break down organophosphonates to harvest phosphorus, carbon, and nitrogen in nutrient-limited niches.
- Rajakovich, Lauren J.,Pandelia, Maria-Eirini,Mitchell, Andrew J.,Chang, Wei-Chen,Zhang, Bo,Boal, Amie K.,Krebs, Carsten,Bollinger, J. Martin
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p. 1627 - 1647
(2019/03/19)
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- Characterization of N,N-dimethyl amino acids by electrospray ionization-tandem mass spectrometry
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Methylation is an essential metabolic process for a number of critical reactions in the body. Methyl groups are involved in the healthy function of the body life processes, by conducting methylation process involving specific enzymes. In these processes, various amino acids are methylated, and the occurrence of methylated amino acids in nature is diverse. Nowadays, mass-spectrometric-based identification of small molecules as biomarkers for diseases is a growing research. Although all dimethyl amino acids are metabolically important molecules, mass spectral data are available only for a few of them in the literature. In this study, we report synthesis and characterization of all dimethyl amino acids, by electrospray ionization-tandem mass spectrometry (MS/MS) experiments on protonated molecules. The MS/MS spectra of all the studied dimethyl amino acids showed preliminary loss of H2O+CO to form corresponding immonium ions. The other product ions in the spectra are highly characteristic of the methyl groups on the nitrogen and side chain of the amino acids. The amino acids, which are isomeric and isobaric with the studied dimethyl amino acids, gave distinctive MS/MS spectra. The study also included MS/MS analysis of immonium ions of dimethyl amino acids that provide information on side chain structure, and it is further tested to determine the N-terminal amino acid of the peptides.
- Naresh Chary,Sudarshana Reddy,Kumar, Ch. Dinesh,Srinivas,Prabhakar
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p. 771 - 781
(2015/08/18)
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- Novel Isobaric Tandem Mass Tags for Quantitative Proteomics and Peptidomics
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Compositions and methods of tagging peptides and other molecules using novel isobaric tandem mass tagging reagents, including novel N,N-dimethylated amino acid 8-plex and 16-plex isobaric tandem mass tagging reagents. The tagging reagents comprise: a) a reporter group having at least one atom that is optionally isotopically labeled; b) a balancing group, also having at least one atom that is optionally isotopically labeled, and c) an amine reactive group. The tagging reagents disclosed herein serve as attractive alternatives for isobaric tag for relative and absolute quantitation (iTRAQ) and tandem mass tags (TMTs) due to their synthetic simplicity, labeling efficiency and improved fragmentation efficiency.
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- Catalyst-free one-pot reductive alkylation of primary and secondary amines and N,N-dimethylation of amino acids using sodium borohydride in 2,2,2-trifluoroethanol
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A simple and convenient procedure for the reductive alkylation of primary and secondary amines and N,N-dimethylation of amino acids is described using sodium borohydride as a reducing agent in 2,2,2- trifluoroethanol without use of a catalyst or any other additive. The solvent can be readily recovered from reaction products in excellent purity for direct reuse. Georg Thieme Verlag Stuttgart - New York.
- Tajbakhsh, Mahmood,Hosseinzadeh, Rahman,Alinezhad, Heshmatollah,Ghahari, Somayeh,Heydari, Akbar,Khaksar, Samad
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experimental part
p. 490 - 496
(2011/03/20)
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- Reductive methylation of primary and secondary amines and amino acids by aqueous formaldehyde and zinc
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Amines can be methylated when treated with formaldehyde and zinc in aqueous medium. Selective mono- or dimethylation can be achieved by proper choice of pH, stoichiometry and reaction time. This method can also be applied for amino acids.
- da Silva, Renato A.,Estevam, Idália H.S.,Bieber, Lothar W.
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p. 7680 - 7682
(2008/03/30)
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- Stable-isotope dimethylation labeling combined with LC-ESI MS for quantification of amine-containing metabolites in biological samples
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One of the challenges associated with metabolome profiling in complex biological samples is to generate quantitative information on the metabolites of interest. In this work, a targeted metabolome analysis strategy is presented for the quantification of amine-containing metabolites. A dimethylation reaction is used to introduce a stable isotopic tag onto amine-containing metabolites followed by LC-ESI MS analysis. This labeling reaction employs a common reagent, formaldehyde, to label globally the amine groups through reductive animation. The performance of this strategy was investigated in the analysis of 20 amino acids and 15 amines by LC-ESI MS. It is shown that the labeling chemistry is simple, fast (13C-dimethylation does not show any isotope effect on either RPLC or HILIC LC, indicating that 13C-labeling is a preferred approach for relative quantification of amine-containing metabolites in different samples. The isotopically labeled 35 amine-containing analogues were found to be stable and proved to be effective in overcoming matrix effects in both relative and absolute quantification of these analytes present in a complicated sample, human urine. Finally, the characteristic mass difference provides additional structural information that reveals the existence of primary or secondary amine functional groups in amine-containing metabolites. As an example, for a human urine sample, a total of 438 pairs of different amine-containing metabolites were detected, at signal-to-noise ratios of greater than 10, by using the labeling strategy in conjunction with RP LC-ESI Fourier-transform ion cyclotron resonance MS.
- Guo, Kevin,Ji, Chengjie,Li, Liang
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p. 8631 - 8638
(2008/03/15)
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- HIGHLY CONCENTRATED AQUEOUS SOLUTIONS OF N,N-DIALKYLGLYCINES AND PROCESS FOR PREPARATION THEREOF
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An aqueous high-concentration solution of N,N-dialkylglycine, economical, easy to handle, and useful for subsequent organic chemical reactions, is provided. Also is provided a process for production thereof. The aqueous high-concentration solution of N,N-dialkylglycine which contains the N,N-dialkylglycine at a concentration of 30-80 % by mass, and a metal-mineral acid salt at a content of 0.3-3 % by mass can be produced industrially from an aqueous N,N-dialkylglycine alkali metal salt as the source material by the steps of(i) neutralizing an aqueous solution of an N,N-dialkylglycine alkali metal salt with a mineral acid,(ii) condensing the obtained aqueous solution by removal of water, and(iii) separating by solid-liquid separation the deposited alkali metal-mineral acid salt from the resulting slurry of the aqueous N,N-dialkylglycine solution and the alkali metal-mineral acid salt.
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- Solid-phase synthesis of five-dimensional libraries via a tandem Petasis-Ugi multi-component condensation reaction
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Five-dimensional libraries of dipeptide amides are readily prepared using a solid-phase tandem Petasis-Ugi multi-component condensation protocol on either a RINK amine or Universal RINK isonitrile resin. The method is practical and can be automated to prepare a large number of compounds useful for high throughput biological screening.
- Portlock, David E.,Naskar, Dinabandhu,West, Laura,Ostaszewski, Ryszard,Chen, Jack J.
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p. 5121 - 5124
(2007/10/03)
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- A tandem Petasis-Ugi multi component condensation reaction: Solution phase synthesis of six dimensional libraries
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Amino acids with three points of diversity generated from the Petasis boronic acid-Mannich reaction can be used as one of the four components of the Ugi condensation to prepare six dimensional libraries of dipeptide amides.
- Portlock, David E.,Ostaszewski, Ryszard,Naskar, Dinabandhu,West, Laura
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p. 603 - 605
(2007/10/03)
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- Method for producing an n-alkyl-alpha-dialkyl-aminoacethohydroxamic acid compound
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There is disclosed a method for producing an N-alkyl-α-dialkylaminoacetohydroxamic acid compound represented by formula (2), which comprises reacting an α-dialkylaminoacetic acid ester compound represented by formula (1) with an N-alkylhydroxylamine, wherein the reaction is carried out in water and an ether-series organic solvent, STR1 wherein R1, R2, R3 and R4, which are the same or different, each represents an alkyl group. According to the method, it is possible to obtain the objective compound in a high yield with a short reaction time, with restrained formation of a by-product.
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- Syntheses of 1,2-di-O -palmitoyl-sn -glycero-3-phosphocholine (DPPC) and analogs with 13C- and 2H-labeled choline head groups
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The syntheses of four head group labeled analogs of 1,2-di-O-palmitoyl-sn-glycero-3-phosphoc (DPPC) (6) by a general method from 1,2-di-O-palmitoyl-sn -glycero-3-phosphatidic acid (5) have been performed. The syntheses of 1,2-di-O-palmitoyl-sn-glycero-3-phospho[α-13C]choline (6a) and 1,2-di-O-palmitoyl-sn-glycero-3-phospho[β13C]choline (6b) were performed from labeled [l-13C]glycine (1a) in 52% overall yield and from [2-13C]glycine (1b) in 56% overall yield, respectively. 1,2-Di-O-palmitoyl-sn-glycero-3-phosphol[N(C2H3)3]choline (9) was prepared from 2-aminoethanol in 39% overall yield. 1,2-Di- O-palmitoyl-sn-glycero-3-phospho[α-C2H2]choline (12) was prepared from N,N-dimethylglycine ethyl ester in 50% overall yield.
- Lin, Sonyuan,Duclos Jr., Richard I.,Makriyannis, Alexandros
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p. 171 - 181
(2007/10/03)
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- Degenerate Transesterification of 3,5-Dimethylphenolate/3,5-Dimethylphenyl Esters in Weakly Polar, Aprotic Solvents. Reactions of Aggregates and Complex-Induced Proximity Effects
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The rates of exchange of the 3,5-dimethylphenolate ion between lithium 3,5-dimethylphenolate-d6 and a series of 3,5-dimethylphenyl esters have been determined in the weakly polar, aprotic solvents dioxolane, dimethoxyethane (DME), tetrahydrofuran (THF), and pyridine. The esters include the propionate, butyrate, methoxyacctate, β-methoxypropionate, 4-methoxybutyrate, 2-tetrahydrofuroate, 2-furoate, (N,N-dimethylamino)acetate, (methylthio)acetate, 2- and 4-pyridine-carboxylates, 2-pyridylacetate, 4-pyridylacetate, phenylacetate, andp-methoxy-,p-chloro-, and p-(trifluoromethyl)phenylacetates. The rates and kinetic orders of the reactions of 3,5-dimethylphenyl propionate in various solvents at 35°C gave the following second-order rate constants (104k2, L mol-1 sec-1) for the following major aggregate species: THF tetramer, 6.5; DME tetramer, 3.3 (40°C); dioxolane, 13, hexamer, 71; pyridine tetramer, 2.2, dimer, 29. For 3,5-dimethylphenyl β-methoxypropionate, the order of reactivity is dioxolane > DME > THF. These results are interpreted in terms of a preequilibrium in which a solvent on lithium in the tetramer is replaced by the ester. The rates of transesterification have been compared with the rates of hydrolysis in 30% aqueous ethanol for the above series of esters. Those esters that have a second Lewis base center proximal to the ester function show significantly increased reactivity in transesterification, which is attributed to a complex-induced proximity effect.
- Jackman,Petrei,Smith
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p. 3451 - 3458
(2007/10/02)
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- A systematic entropy relationship for the general-base catalysis of the deprotonation of a carbon acid. A quantitative probe of transition-state solvation
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The general-base-catalyzed deprotonation of a carbon acid, the l-methyl-4-(phenylacetyl)pyridinium cation (pKa = 9.02 at 25 °C), has been investigated for 32 general-base catalysts (25 amines and seven phenoxide ions) in aqueous solution. Amines give a generally scattered Bronsted plot; ring-substituted benzylamines have ?= 0.52, and ring-substituted phenoxides have ?= 0.60, with the phenoxides being more reactive than amines of similar basicity. The temperature dependences of the general-base-catalyzed deprotonation of this carbon acid have been measured over the range 15-45 °C for 12 base catalysts (eight primary, secondary, and tertiary amines; 4-(dimethylamino)pyridine; two phenoxide ions; hydroxide ion). The entropies of activation for these deprotonations show a clean curvilinear dependence upon the entropies of protonation of these base species, with the hydroxide ion being the only significant deviant from this relationship. This observation quantitatively establishes the importance of solvation effects as the major source of deviations that are commonly observed in Bronsted relationships for general-base-catalyzed processes.
- Bunting, John W.,Stefanidis, Dimitrios
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p. 779 - 786
(2007/10/02)
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- Anodic Oxidation of Amines. IX. Anodic Oxidation Process of α-Amino Acids in Aqueous Buffer of pH 10
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Anodic oxidation of α-amino acids with and without a β-hydroxy group was investigated by cyclic voltammetry and controlled potential electrolysis in aqueous carbonate buffer of pH 10.The first wave of the α-amino acids is developed at nearly the same potentials as those observed for the corresponding simple aliphatic amines, showing that a β-hydroxy group does not significantly decrease the first oxidation potential, in contrast to the case of β-alkanolamines.Decarboxylation accompanied by dealkylation is the main reaction process, and a small amount of C-C bond fission also occurs only in the case of the β-hydroxy amino acids.Keywords - α-amino acid; anodic oxidation; decarboxylation; carbon-nitrogen bond fission; carbon-carbon bond fission; aldehyde; N-methyl-α-amino acid; N,N-dimethyl-α-amino acid.
- Masui, Masaichiro,Kamada, Yoshiyuki,Iizuka, Taeko,Ozaki, Shigeko
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p. 4740 - 4745
(2007/10/02)
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- Diphenylboron Chelates of α-(Dialkylamino)carboxylic Acids and their N-Oxides
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α-(Dialkylamino)carboxylic acids and their N-oxides react with oxybis(diphenylborane) or similar diphenylborane derivatives to give five- or six-membered diphenylboron chelate rings, respectively, the structure of which is supported by spectroscopic evidence.
- Kliegel, Wolfgang,Graumann, Juergen
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p. 950 - 961
(2007/10/02)
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