- A Single Atom Change Facilitates the Membrane Transport of Green Fluorescent Proteins in Mammalian Cells
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Direct delivery of proteins into mammalian cells is a challenging problem in biological and biomedical applications. The most common strategies for the delivery of proteins into the cells include the use of cell-penetrating peptides or supercharged proteins. Herein, we show for the first time that a single atom change, hydrogen to halogen, at one of the tyrosine residues can increase the cellular entry of ～28 kDa green fluorescent protein (GFP) in mammalian cells. The protein uptake is facilitated by a receptor-mediated endocytosis and the cargo can be released effectively into cytosol by co-treatment with the endosomolytic peptide ppTG21.
- Jakka, Surendar R.,Govindaraj, Vijayakumar,Mugesh, Govindasamy
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- Biocascade Synthesis of L-Tyrosine Derivatives by Coupling a Thermophilic Tyrosine Phenol-Lyase and L-Lactate Oxidase
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A one-pot biocascade of two enzymatic steps catalyzed by an l-lactate oxidase and a tyrosine phenol-lyase has been successfully developed in the present study. The reaction provides an efficient method for the synthesis of l-tyrosine derivatives, which exhibits readily available starting materials and excellent yields. In the first step, an in situ generation of pyruvate from readily available bio-based l-lactate catalyzed by a highly active l-lactate oxidase from Aerococcus viridans (AvLOX) was developed (using oxygen as oxidant and catalase as hydrogen peroxide removing reagent). Pyruvate thus produced underwent C–C coupling with phenol derivatives as acceptor substrate using specially designed thermophilic tyrosine phenol-lyase mutants from Symbiobacterium toebii (TTPL). Overall, this cascade avoids the high cost and easy decomposition of pyruvate and offered an efficient and environmentally friendly procedure for l-tyrosine derivatives synthesis.
- Jiang, Yiqi,Ju, Shuyun,Li, Guosi,Lian, Jiazhang,Lin, Jianping,Wu, Mianbin,Xue, Hailong,Yang, Lirong
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supporting information
(2020/02/25)
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- Synthesis and trypanocide activity of chloro-l-tyrosine and bromo-l-tyrosine derivatives
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Twenty-two halogenated l-tyrosine derivatives were synthesized to examine new substances for the treatment of Chagas disease. The synthesis of these derivatives with different degree of substitution in the amino group with methyl iodide, giving primary, tertiary, and quaternary amino acids. All compounds were tested in vitro against intracellular amastigotes of Trypanosoma cruzi, and the cytotoxicity were evaluated over monocytic cell line U-937. Compound 25 was the most active against T. cruzi with a EC50 of 75.52 μM compared with benznidazole with a EC50 of 58.79 μM. Compounds 3, 4, 7, and 15 were the derivatives with the best selectivity index (SI) with values of 7.5, 8.3,12.1, and 8.6, respectively. Finally, compound 7 was the safer and the more promising derivative against T. cruzi.
- Pastrana Restrepo, Manuel,Galeano Jaramillo, Elkin,Martínez Martínez, Alejandro,Robledo Restrepo, Sara
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p. 2454 - 2465
(2018/10/02)
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- Anti-parasite and cytotoxic activities of chloro and bromo L-tyrosine derivatives
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A series of twenty-one L-tyrosine derivatives with modifications in the halogenation pattern of the aromatic ring and different degree of methylations on the amine and phenolic hydroxyl groups were synthesized. The structures of all the intermediates and target compounds were confirmed unambiguous by spectroscopy analysis. Additionally, all compounds were evaluated against Plasmodium falciparum and Leishmania panamensis parasites between 20-702 μg mL-1. The cytotoxic evaluation was done to determine the selectivity index for each compound. Six compounds had the lower EC50 (effective concentration 50) against L. panamensis. One of these compounds was the most active with an EC50 at 24.13 μg mL-1 (76.07 μM). All derivatives showed no significant activity against P. falciparum and no compound has in vitro antifungal activity at 500 μg mL-1.
- Restrepo, Manuel Pastrana,Jaramillo, Elkin Galeano,Martínez, Alejandro Martínez,Arango, Ana Mesa,Restrepo, Sara Robledo
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p. 2569 - 2579
(2018/11/06)
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- Biocatalytic One-Pot Synthesis of l-Tyrosine Derivatives from Monosubstituted Benzenes, Pyruvate, and Ammonia
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l-Tyrosine derivatives were obtained in >97% ee via a biocatalytic one-pot two-step cascade using substituted benzenes, pyruvate, and NH3 as starting materials. In the first step, monosubstituted arenes were regioselectively hydroxylated in the o-position by monooxygenase P450 BM3 (using O2 as oxidant with NADPH-recycling) to yield the corresponding phenols, which subsequently underwent C-C coupling and simultaneous asymmetric amination with pyruvate and NH3 using tyrosine phenol lyase to furnish l-DOPA surrogates in up to 5.2 g L-1. Instead of analytically pure arenes, crude aromatic gasoline blends containing toluene were used to yield 3-methyl-l-tyrosine in excellent yield (2 g L-1) and >97% ee.
- Dennig, Alexander,Busto, Eduardo,Kroutil, Wolfgang,Faber, Kurt
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p. 7503 - 7506
(2015/12/11)
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- Vinylation of Unprotected Phenols Using a Biocatalytic System
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Readily available substituted phenols were coupled with pyruvate in buffer solution under atmospheric conditions to afford the corresponding para-vinylphenol derivatives while releasing only one molecule of CO2 and water as the by-products. This transformation was achieved by designing a biocatalytic system that combines three biocatalytic steps, namely the C-C coupling of phenol and pyruvate in the presence of ammonia, which leads to the corresponding tyrosine derivative, followed by deamination and decarboxylation. The biocatalytic transformation proceeded with high regioselectivity and afforded exclusively the desired para products. This method thus represents an environmentally friendly approach for the direct vinylation of readily available 2-, 3-, or 2,3-disubstituted phenols on preparative scale (0.5 mmol) that provides vinylphenols in high yields (65-83%).
- Busto, Eduardo,Simon, Robert C.,Kroutil, Wolfgang
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supporting information
p. 10899 - 10902
(2015/09/15)
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- ApoE secretion modulating bromotyrosine derivative from the Australian marine sponge Callyspongia sp.
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High throughput screening of a pre-fractionated natural product library identified 11 active fractions showing ApoE modulation activity. Mass-directed fractionation of one active crude extract from the Australian marine sponge Callyspongia sp. resulted in the isolation of 13 metabolites, including three new bromotyrosine derivatives, callyspongic acid (1), 3,5-dibromo-4-methoxyphenylpyruvic acid (2), N-acetyl-3-bromo-4-hydroxylphenylethamine (3), and ten known compounds (4-13). The structure elucidation of compounds 1-3 was based on their 1D and 2D NMR and MS spectroscopic data. 3,5-Dibromo-4-methoxyphenylpyruvic acid (2) showed weak activity in increasing the apolipoprotein E secretion from human CCF-STTG1 cells at the concentration of 40 μM.
- Tian, Li-Wen,Feng, Yunjiang,Shimizu, Yoko,Pfeifer, Tom A.,Wellington, Cheryl,Hooper, John N.A.,Quinn, Ronald J.
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supporting information
p. 3537 - 3540
(2015/02/19)
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- ApoE secretion modulating bromotyrosine derivative from the Australian marine sponge Callyspongia sp.
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High throughput screening of a pre-fractionated natural product library identified 11 active fractions showing ApoE modulation activity. Mass-directed fractionation of one active crude extract from the Australian marine sponge Callyspongia sp. resulted in the isolation of 13 metabolites, including three new bromotyrosine derivatives, callyspongic acid (1), 3,5-dibromo-4- methoxyphenylpyruvic acid (2), N-acetyl-3-bromo-4-hydroxylphenylethamine (3), and ten known compounds (4-13). The structure elucidation of compounds 1-3 was based on their 1D and 2D NMR and MS spectroscopic data. 3,5-Dibromo-4- methoxyphenylpyruvic acid (2) showed weak activity in increasing the apolipoprotein E secretion from human CCF-STTG1 cells at the concentration of 40 μM.
- Tian, Li-Wen,Feng, Yunjiang,Shimizu, Yoko,Pfeifer, Tom A.,Wellington, Cheryl,Hooper, John N.A.,Quinn, Ronald J.
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supporting information
p. 3537 - 3540
(2014/07/22)
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- Preparation of 3-bromo-l-tyrosine and 3,5-dibromo-l-tyrosine
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l-Tyrosine is converted to 3-bromo-l-tyrosine in good yield by reaction with 1.2 equiv. of DMSO in HBr/AcOH, while reaction with 2.2 equiv. of DMSO under comparable conditions results in formation of 3,5-dibromo-l-tyrosine in good yield. This is the simplest, safest and most efficient method for the preparation of gram quantities of either 3-bromo-l-tyrosine or 3,5-dibromo-l-tyrosine.
- Phillips, Robert S.,Busby, Susan,Edenfield, Leia,Wickware, Kevin
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p. 529 - 532
(2013/07/27)
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- (S)-3-(4-(2-(5-Methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)-2-(piperazin-1-yl)propanoic acid compounds: Synthesis and biological evaluation of dual PPARα/γ agonists
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A series of novel, potent PPARα/γ dual agonists were synthesized and appraised. The most potent analogue, compound 2b demonstrated EC50 value of 0.012 ± 0.002 and 0.032 ± 0.01 μM, respectively, for hPPARα and hPPARγ in transactivation assay. Additionally, compound 2b demonstrated good glucose and lipid lowering effect in genetic diabetic (db/db) mice.
- Zhou, Xinbo,Chen, Wei,Xu, Cheng,Fan, Shiyong,Xie, Yunde,Zhong, Wu,Wang, Lili,Li, Song
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scheme or table
p. 2605 - 2608
(2010/06/17)
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- Substitued A-Piperazingly Phenylpropionic Acid Derivatives As Hppar Alpha And/Or Hppar Gamma Agonists
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The present invention relates to a compound of formula I, racemates, optically active isomers, or pharmaceutically acceptable salts or solvates thereof, and a pharmaceutical composition comprising the compound, the various radicals in the formula I are the same as defined in the claims. The present invention also relates to a process for preparing the compound of formula I and use of said compound in the preparation of a medicament for the treatment of hyperglycemia, dyslipidemia, type II diabetes mellitus including associated diabetic dyslipidemia
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Page/Page column 8
(2008/06/13)
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- Chemistry of unprotected amino acids in aqueous solution: Direct bromination of aromatic amino acids with bromoisocyanuric acid sodium salt under strong acidic condition
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Brominations of unprotected aromatic amino acids such as phenylalanine, tyrosine, and glycine, with bromoisocyanuric acid mono sodium salt (BICA-Na) were conducted in 60% aq. H2SO4 at 0°C to give a mixture of mono-brominated products in good yield. Unexpectedly, meta-bromophenylglycine was obtained as main product accompanied by ortho- and para-substituted products, while phenylalanine gave only ortho- and para-substituted products. Bromination of 2-phenylethylamine or benzylamine showed a tendency similar to the corresponding amino acids.
- Yokoyama, Yuusaku,Yamaguchi, Tomotsugu,Sato, Masanori,Kobayashi, Eri,Murakami, Yasuoki,Okuno, Hiroaki
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p. 1715 - 1719
(2007/10/03)
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