- Design, synthesis, and molecular docking studies of N-(9,10-anthraquinone-2-carbonyl)amino acid derivatives as xanthine oxidase inhibitors
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A series of N-(9,10-anthraquinone-2-carbonyl)amino acid derivatives (1a–j) was designed and synthesized as novel xanthine oxidase inhibitors. Among them, the L/D-phenylalanine derivatives (1d and 1i) and the L/D-tryptophan derivatives (1e and 1j) were effective with micromolar level potency. In particular, the L-phenylalanine derivative 1d (IC50?=?3.0?μm) and the D-phenylalanine derivative 1i (IC50?=?2.9?μm) presented the highest potency and were both more potent than the positive control allopurinol (IC50?=?8.1?μm). Preliminary SAR analysis pointed that an aromatic amino acid fragment, for example, phenylalanine or tryptophan, was essential for the inhibition; the D-amino acid derivative presented equal or greater potency compared to its L-enantiomer; and the 9,10-anthraquinone moiety was welcome for the inhibition. Molecular simulations provided rational binding models for compounds 1d and 1i in the xanthine oxidase active pocket. As a result, compounds 1d and 1i could be promising lead compounds for further investigation.
- Zhang, Ting-Jian,Li, Song-Ye,Yuan, Wei-Yan,Zhang, Yi,Meng, Fan-Hao
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p. 893 - 901
(2018/03/21)
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- In situ deprotection and incorporation of unnatural amino acids during cell-free protein synthesis
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The S30 extract from E. coli BL21 Star (DE3) used for cell-free protein synthesis removes a wide range of α-amino acid protecting groups by cleaving α-carboxyl hydrazides; methyl, benzyl, tert-butyl, and adamantyl esters; tert-butyl and adamantyl carboxamides; α-amino form-, acet-, trifluoroacet-, and benzamides and sidechain hydrazides and esters. The free amino acids are produced and incorporated into a protein under standard conditions. This approach allows the deprotection of amino acids to be carried out in situ to avoid separate processing steps. The advantages of this approach are demonstrated by the efficient incorporation of the chemically intractable (S)-4-fluoroleucine, (S)-4,5- dehydroleucine, and (2S,3R)-4-chlorovaline into a protein through the direct use of their respective precursors, namely, (S)-4-fluoroleucine hydrazide, (S)-4,5-dehydroleucine hydrazide, and (2S,3R)-4-chlorovaline methyl ester. These results also show that the fluoroand dehydroleucine and the chlorovaline are incorporated into a protein by the normal biosynthetic machinery as substitutes for leucine and isoleucine, respectively. Copyright
- Arthur, Isaac N.,Hennessy, James E.,Padmakshan, Dharshana,Stigers, Dannon J.,Lesturgez, Stéphanie,Fraser, Samuel A.,Liutkus, Mantas,Otting, Gottfried,Oakeshott, John G.,Easton, Christopher J.
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supporting information
p. 6824 - 6830
(2013/06/26)
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- Microbial enantioselective removal of the N-benzyloxycarbonyl amino protecting group
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In order to deprotect N-carbobenzoxy-l-aminoacids (Cbz-AA) and related compounds, a series of microorganisms was selected from soil by enrichment cultures with Cbz-l-Glu as sole nitrogen source. A lyophilized whole-cell preparation of two Arthrobacter sp. strains grown on Cbz-Glu or Cbz-Gly exhibited a high cleavage activity. The conditions of hydrolysis have been optimized and a quantitative enantioselective deprotection of several Cbz-dl-amino acids was obtained, as well as the deprotection of N-carbamoylester derivatives of several synthetic amino compounds. The preparation of Cbz-d-allylglycine and l-allylglycine in high yield and high optical purity is described as an application of this method.
- Maurs, Michele,Acher, Francine,Azerad, Robert
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- Phototriggering of neuroactive amino acids from 5,6-benzocoumarinyl conjugates
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Uncaging of several neuroactive amino acids, namely β-alanine, tyrosine, 3,4-dihydroxyphenylalanine (DOPA) and glutamic acid from the corresponding 5,6-benzocoumarinyl conjugates was carried out by irradiation at different wavelengths and in different solvent systems. The release of the various amino acids was faster in ACN/HEPES buffer mixtures and for the tyrosine conjugate, an increase in the photolysis reaction rates and the quantitative uncaging of the amino acid was associated with increasing water content in the solvent mixture.
- Fernandes, Maria José G.,Costa, Susana P.G.,Gonalves, M. Sameiro T.
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experimental part
p. 2422 - 2426
(2011/05/06)
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- Concentration dependent transformation of oligopeptide based nanovesicles to nanotubes and an application of nanovesicles
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The concentration dependent transformation of an oligopeptide nanostructure from nanovesicles to nanotubes at neutral pH is presented. The oligopeptide Acp-Tyr-Glu (Acp: 6-aminohexanoic acid) forms nanovesicles at a concentration of 6.9 mgmL-1. At a concentration of 2.3 mgmL-1 these vesicular structures completely disappear and nanotubular structures are observed. We have also successfully optimized an intermediate concentration (3.4 mgmL-1) where an ordered array of fused vesicular structures are formed, which actually leads to the transition from nanovesicles to nanotubes. These vesicular structures are very much sensitive toward metal ions and pH. Biocompatible calcium ions and high pH (10.7) can trigger the rupturing of these nanovesicles. One important property of these nanovesicular structures is the encapsulation of a potent anticancer drug doxorubicin, which can also be released in the presence of calcium ions promising a future use of these nanovesicles as vehicles for carrying biologically important molecules.
- Naskar, Jishu,Banerjee, Arindam
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experimental part
p. 1817 - 1823
(2010/04/30)
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- The Demonstration of Selective Peptide Bond Formation in Clear Aqueous Solutions
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The distribution of dipeptides upon treatment of equimolar amounts of glutamic acid, leucine, and C6H11N=C=N(CH2)3+NMe3-OSO2C6H4Me-p, in clear aqueous solution followed by N,C-protection, was found to be: Bz-Glu(γ-OMe)-Leu-OMe (72percent), Bz-Glu(α-OMe)-Glu-di-OMe (15percent), and Bz-Leu-Leu-OMe (8percent); Bz-Leu-Glu-di-OMe, Bz-Glu(α-OMe)-Leu-OMe, and Bz-Glu(γ-OMe)-Glu-di-OMe could not be detected (Bz = PhCO).
- Ranganathan, Darshan,Singh, Girij Pal
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p. 142 - 143
(2007/10/02)
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