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https://www.readbyqxmd.com/read/28318003/small-molecule-hedgehog-pathway-antagonists
#1
Trieu N Trinh, Eileen A McLaughlin, Christopher P Gordon, Ilana R Bernstein, Victoria J Pye, Kate A Redgrove, Adam McCluskey
Leveraging our quinolone-1-(2H)-one based Hedgehog signalling pathway (HSP) inhibitors we have developed two new classes of HSP inhibitors based on: l-tryptophan and benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amine. Synthesis of focused compound libraries identified six l-tryptophan based inhibitors, and two stimulators, of Gli at 10 μM compound concentration. 2,4-Dichloro-13 and indole 16 suppressed mRNA expression of Ptch1 in Shh LIGHT2 cells, with 13 suppressing and 16 stimulating Gli2 mRNA expression...
March 20, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28302759/preclinical-evaluation-of-11-c-sarcosine-as-a-substrate-of-proton-coupled-amino-acid-transporters-and-first-human-application-in-prostate-cancer
#2
Morand Piert, Xia Shao, David M Raffel, Mathew S Davenport, Jeffrey Montgomery, Lakshmi Kunju, Brian G Hockley, Javed Siddiqui, Peter J H Scott, Arul Chinnaiyan, Thekkelnaycke Rajandiran
Sarcosine is a known substrate of proton-coupled amino acid transporters (PAT), which are overexpressed in selected tissues and solid tumors. Sarcosine, an N-methyl derivative of the amino acid glycine and a metabolic product of choline, plays an important role for prostate cancer aggressiveness and progression. Methods: Carbon-11 radiolabeled sarcosine ((11)C-sarcosine) was tested as a new positron emission tomography (PET) imaging probe in comparison with (11)C-choline in two prostate cancer tumor xenograft models (DU-145 and PC-3)...
March 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28298987/effect-of-different-concentrations-of-specific-inhibitor-of-matrix-metalloproteinases-on-the-shear-bond-strength-of-self-adhesive-resin-cements-to-dentin
#3
Mohammad-Esmaeel Ebrahimi-Chaharom, Mehdi Abed-Kahnamoui, Mahmoud Bahari, Hamed Hamishehkar, Mahya Gharouni
BACKGROUND: Considering the probability of chemical and enzymatic reactions between matrix metalloproteinases (MMPs) in the dentin structure and their specific inhibitors, the aim of the present study was to evaluate the effect of different concentrations of specific inhibitor of MMPs (galardin) on the shear bond strength of self-adhesive resin cements to dentin. MATERIAL AND METHODS: Forty-eight sound human premolars were mounted in self-cured acrylic resin after removal of the enamel on the buccal and lingual surfaces...
March 2017: Journal of Clinical and Experimental Dentistry
https://www.readbyqxmd.com/read/28286019/methotrexate-causes-acute-hyperplasia-of-enterochromaffin-cells-containing-substance-p-in-the-intestinal-mucosa-of-rats
#4
Takuji Machida, Yuho Takano, Kenji Iizuka, Maiko Machida, Masahiko Hirafuji
This study aimed to investigate the acute and chronic effect of methotrexate on the intestinal substance P metabolism after a single administration to rats. Methotrexate caused a significant increase in the number of substance P-containing cells in the ileal mucosa both at 24 and 96 h. Most of enterochromaffin cells expressing l-tryptophan hydroxylase contained substance P. The expression of Tac1 mRNA was increased by methotrexate at 24 h, but not at 96 h. Thus, methotrexate causes acute hyperplasia of enterochromaffin cells in the intestinal mucosa of rats with a transient increase in the production of substance P...
February 22, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28283907/nanoparticles-generated-from-a-tryptophan-derivative-physical-characterization-and-anti-cancer-drug-delivery
#5
Taru Dube, Saurabh Mandal, Jiban Jyoti Panda
Surging reports of peptide-based nanosystems and their growing potency in terms of biological utility demand for the search of newer and simpler peptide-based systems that could serve as smart templates for the development of self-assembled nanostructures. Use of simple amino acids as monomeric building blocks for synthesizing ensembles of nanostructures have gained momentum in this direction with some reports focusing on the development of nanosystems from single or modified single amino acids. In this work, we have demonstrated self-assembly and nanoparticle formation ability of a single amino acid derivative, N-alpha-(9-fluorenylmethyloxycarbonyl)-N(in)-tert-butyloxycarbonyl-L-tryptophan [Fmoc-Trp(Boc)-OH]...
March 10, 2017: Amino Acids
https://www.readbyqxmd.com/read/28275295/investigation-of-mitigating-effect-of-colon-specific-prodrugs-of-boswellic-acid-on-2-4-6-trinitrobenzene-sulfonic-acid-induced-colitis-in-wistar-rats-design-kinetics-and-biological-evaluation
#6
Ajinkya Sarkate, Suneela S Dhaneshwar
AIM: To develop a colon-targeting bioreversible delivery system for β-boswellic acid (BBA) and explore utility of its prodrugs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. METHODS: Synthesis of 4 co-drugs of BBA with essential amino acids was achieved by CDI coupling, followed by their spectral characterization. In vitro kinetics were studied by HPLC in aqueous buffers, homogenates of gastrointestinal tract and fecal matter. In vivo kinetic studies were performed in Wistar rat plasma, urine and feces...
February 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28268250/antioxidant-effect-of-thiazolidine-molecules-in-cell-culture-media-improves-stability-and-performance
#7
Jennifer Kuschelewski, Alisa Schnellbaecher, Sascha Pering, Maria Wehsling, Aline Zimmer
The ability of cell culture media components to generate reactive species as well as their sensitivity to oxidative degradation, affects the overall stability of media and the behavior of cells cultured in vitro. This study investigates the influence of thiazolidine molecules, formed from the condensation between cysteine and alpha-ketoacids, on the stability of these complex mixtures and on the performance of cell culture processes aiming to produce therapeutically relevant monoclonal antibodies. Results presented in this study indicate that 2-methyl-1,3-thiazolidine-2,4-dicarboxylic acid and 2-(2-carboxyethyl)-1,3-thiazolidine-2,4-dicarboxylic acid, obtained by condensation of cysteine with pyruvate or alpha-ketoglutarate respectively, are able to stabilize cell culture media formulations, in particular redox sensitive molecules like folic acid, thiamine, L-methionine (met) and L-tryptophan (trp)...
March 7, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28214225/a-relay-pathway-between-arginine-and-tryptophan-metabolism-confers-immunosuppressive-properties-on-dendritic-cells
#8
Giada Mondanelli, Roberta Bianchi, Maria Teresa Pallotta, Ciriana Orabona, Elisa Albini, Alberta Iacono, Maria Laura Belladonna, Carmine Vacca, Francesca Fallarino, Antonio Macchiarulo, Stefano Ugel, Vincenzo Bronte, Federica Gevi, Lello Zolla, Auke Verhaar, Maikel Peppelenbosch, Emilia Maria Cristina Mazza, Silvio Bicciato, Yasmina Laouar, Laura Santambrogio, Paolo Puccetti, Claudia Volpi, Ursula Grohmann
Arginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunoregulatory enzymes catalyzing the degradation of l-arginine and l-tryptophan, respectively, resulting in local amino acid deprivation. In addition, unlike Arg1, IDO1 is also endowed with non-enzymatic signaling activity in dendritic cells (DCs). Despite considerable knowledge of their individual biology, no integrated functions of Arg1 and IDO1 have been reported yet. We found that IDO1 phosphorylation and consequent activation of IDO1 signaling in DCs was strictly dependent on prior expression of Arg1 and Arg1-dependent production of polyamines...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28211258/effects-of-a-wide-range-of-dietary-nicotinamide-riboside-nr-concentrations-on-metabolic-flexibility-and-white-adipose-tissue-wat-of-mice-fed-a-mildly-obesogenic-diet
#9
Wenbiao Shi, Maria A Hegeman, Dorien A M van Dartel, Jing Tang, Manuel Suarez, Hans Swarts, Bart van der Hee, Lluis Arola, Jaap Keijer
SCOPE: Metabolic flexibility is the ability to switch metabolism between carbohydrate oxidation (CHO) and fatty acid oxidation (FAO) and is a biomarker for metabolic health. The effect on metabolic health of nicotinamide riboside (NR) as an exclusive source of vitamin B3 is unknown and is examined here for a wide range of NR. DESIGN AND METHODS: Nine-week-old male C57BL/6JRcc mice received a semi-purified mildly obesogenic (40 en% fat) diet containing 0.14% L-tryptophan and either 5, 15, 30, 180 or 900 mg NR per kg diet for 15 weeks...
February 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28195396/development-of-a-validated-strategy-for-the-determination-of-tryptamine-in-human-cerebrospinal-fluid-in-the-presence-of-competitors-using-molecularly-imprinted-polymers
#10
Piotr Luliński, Magdalena Bamburowicz-Klimkowska, Mariusz Dana, Dorota Maciejewska
This study presents a validated strategy for the determination of tryptamine in the presence of its competitors, which involves the molecularly imprinted solid-phase extractions combined with high-performance liquid chromatography coupled with fluorimetric detection Tryptamine-imprinted microscale sorbent was produced from 4-vinylbenzoic acid and ethylene glycol dimethacrylate in methanol by precipitation polymerization, and its imprinting factor was equal to 15.4 in static experiments or 18.6 in dynamic binding experiments...
February 14, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28193333/heterologous-expression-of-%C3%AE-glutamyl-transpeptidase-from-bacillus-atrophaeus-gs-16-and-its-application-in-the-synthesis-of-%C3%AE-d-glutamyl-l-tryptophan-a-known-immunomodulatory-peptide
#11
Meenu Saini, Shruti Bindal, Rani Gupta
Gamma-glutamyl transpeptidase from a mesophilic bacterium Bacillus atrophaeus GS-16 (BaGGT) was expressed heterologously in E. coli using pET-51b vector. Maximum production of BaGGT was obtained at 16°C after 16h of IPTG induction and the protein, in its native conformation, was active as a heterooctamer which was composed of four heterodimeric units combined together. One heterodimeric unit constituted two subunits with molecular masses of 45kDa and 21kDa, respectively. The recombinant enzyme was purified by one step His-tag affinity purification protocol with a specific activity of 90U/mg and 5...
April 2017: Enzyme and Microbial Technology
https://www.readbyqxmd.com/read/28192306/a-molecularly-imprinted-polymer-coated-cdte-quantum-dot-nanocomposite-for-tryptophan-recognition-based-on-the-f%C3%A3-rster-resonance-energy-transfer-process
#12
Antonio Tirado-Guizar, Francisco Paraguay-Delgado, Georgina E Pina-Luis
A new 'turn-on' Förster resonance energy transfer (FRET) nanosensor for l-tryptophan based on molecularly imprinted quantum dots (QDs) is proposed. The approach combines the advantages of the molecular imprinting technique, the fluorescent characteristics of the QDs and the energy transfer process. Silica-coated CdTe QDs were first synthesized and then molecularly imprinted using a sol-gel process without surfactants. The final composite presents stable fluorescence which increases with the addition of l-tryptophan...
November 17, 2016: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28166207/structure-and-specificity-of-a-permissive-bacterial-c-prenyltransferase
#13
Sherif I Elshahawi, Hongnan Cao, Khaled A Shaaban, Larissa V Ponomareva, Thangaiah Subramanian, Mark L Farman, H Peter Spielmann, George N Phillips, Jon S Thorson, Shanteri Singh
This study highlights the biochemical and structural characterization of the L-tryptophan C6 C-prenyltransferase (C-PT) PriB from Streptomyces sp. RM-5-8. PriB was found to be uniquely permissive to a diverse array of prenyl donors and acceptors including daptomycin. Two additional PTs also produced novel prenylated daptomycins with improved antibacterial activities over the parent drug.
April 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28161804/tryptophan-depletion-under-conditions-that-imitate-insulin-resistance-enhances-fatty-acid-oxidation-and-induces-endothelial-dysfunction-through-reactive-oxygen-species-dependent-and-independent-pathways
#14
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Georgia Antoniadi, Christos Rountas, Vassilios Liakopoulos, Loannis Stefanidis
In atherosclerosis-associated pathologic entities characterized by malnutrition and inflammation, L-tryptophan (TRP) levels are low. Insulin resistance is an independent cardiovascular risk factor and induces endothelial dysfunction by increasing fatty acid oxidation. It is also associated with inflammation and low TRP levels. Low TRP levels have been related to worse cardiovascular outcome. This study evaluated the effect of TRP depletion on endothelial dysfunction under conditions that imitate insulin resistance...
February 4, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28161779/interactions-of-amino-acids-with-aluminum-octacarboxyphthalocyanine-hydroxide-experimental-and-dft-studies
#15
Marta Kliber-Jasik, Małgorzata A Broda, Anna Maroń, Joanna Nackiewicz
The influence of albumin and amino acids (L-serine, glycine, L-histidine, L-tryptophan, L-cysteine) on the properties of aluminum octacarboxyphthalocyanine hydroxide (Al(OH)PcOC) was investigated in a phosphate buffer (pH 8.0). Particular attention was paid to the spectroscopic properties and photostability of Al(OH)PcOC. The effect of albumin or amino acids on the photodegradation of Al(OH)PcOC was examined in water using red light: 685 nm and daylight irradiation. Analysis of kinetic curves indicated that interaction with those molecules increases the photostability of Al(OH)PcOC...
February 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28138057/biochemical-and-chemical-biology-study-of-rice-ostar1-revealed-that-tryptophan-aminotransferase-is-involved-in-auxin-biosynthesis-identification-of-a-potent-ostar1-inhibitor-pyruvamine2031
#16
Yusuke Kakei, Ayako Nakamura, Mitsuhiro Yamamoto, Yosuke Ishida, Chiaki Yamazaki, Akiko Sato, Megumi Narukawa-Nara, Kazuo Soeno, Yukihisa Shimada
Indole-3-acetic acid (IAA), a major form of auxin, is biosynthesized from L-tryptophan via the indole-3-pyruvic acid (IPyA) pathway in Arabidopsis Tryptophan aminotransferases (TAA1/TARs) catalyze the first step from L-tryptophan to IPyA. In rice, the importance of TAA/TARs or YUC homologs in auxin biosynthesis has been suggested, but the enzymatic activities and involvement of the intermediate IPyA in auxin biosynthesis remain elusive. In this study, we obtained biochemical evidence that the rice tryptophan aminotransferase OsTAR1 converts L-tryptophan to IPyA, and has a Km of 82...
January 30, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28095360/enzyme-catalyzed-michael-addition-for-the-synthesis-of-warfarin-and-its-determination-via-fluorescence-quenching-of-l-tryptophan
#17
Yusheng Yuan, Liu Yang, Shaopu Liu, Jidong Yang, Hui Zhang, Jingjing Yan, Xiaoli Hu
A sensitive fluorescence sensor for warfarin was proposed via quenching the fluorescence of l-tryptophan due to the interaction between warfarin and l-tryptophan. Warfarin, as one of the most effective anticoagulants, was designed and synthesized via lipase from porcine pancreas (PPL) as a biocatalyst to catalyze the Michael addition of 4-hydroxycoumarin to α, β-unsaturated enones in organic medium in the presence of water. Furthermore, the spectrofluorometry was used to detect the concentration of warfarin with a linear range and detection limit (3σ/k) of 0...
January 9, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28089858/glucose-amino-acids-and-fatty-acids-directly-regulate-ghrelin-and-nucb2-nesfatin-1-in-the-intestine-and-hepatopancreas-of-goldfish-carassius-auratus-in-vitro
#18
Juan Ignacio Bertucci, Ayelén Melisa Blanco, Luis Fabián Canosa, Suraj Unniappan
Ghrelin and nesfatin-1 are two peptidyl hormones primarily involved in food intake regulation. We previously reported that the amount of dietary carbohydrates, protein and lipids modulates the expression of these peptides in goldfish in vivo. In the present work, we aimed to characterize the effects of single nutrients on ghrelin and nesfatin-1 in the intestine and hepatopancreas. First, immunolocalization of ghrelin and NUCB2/nesfatin-1 in goldfish hepatopancreas cells was studied by immunohistochemistry. Second, the effects of 2 and 4hour-long exposures of cultured intestine and hepatopancreas sections to glucose, l-tryptophan, oleic acid, linolenic acid (LNA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on ghrelin and nesfatin-1 gene and protein expression were studied...
January 13, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28076364/ifn%C3%AE-regulates-activated-v%C3%AE-2-t-cells-through-a-feedback-mechanism-mediated-by-mesenchymal-stem-cells
#19
Karoline Fechter, Akaitz Dorronsoro, Emma Jakobsson, Izaskun Ferrin, Valérie Lang, Pilar Sepulveda, Daniel J Pennington, César Trigueros
γδ T cells play a role in a wide range of diseases such as autoimmunity and cancer. The majority of circulating human γδ T lymphocytes express a Vγ9Vδ2+ (Vδ2+) T cell receptor (TCR) and following activation release pro-inflammatory cytokines. In this study, we show that IFNγ, produced by Vδ2+ cells, activates mesenchymal stem cell (MSC)-mediated immunosupression, which in turn exerts a negative feedback mechanism on γδ T cell function ranging from cytokine production to proliferation. Importantly, this modulatory effect is limited to a short period of time (<24 hours) post-T cell activation, after which MSCs can no longer exert their immunoregulatory capacity...
2017: PloS One
https://www.readbyqxmd.com/read/28032983/two-flavoenzymes-catalyze-the-post-translational-generation-of-5-chlorotryptophan-and-2-aminovinyl-cysteine-during-nai-107-biosynthesis
#20
Manuel A Ortega, Dillon P Cogan, Subha Mukherjee, Neha Garg, Bo Li, Gabrielle N Thibodeaux, Sonia I Maffioli, Stefano Donadio, Margherita Sosio, Jerome Escano, Leif Smith, Satish K Nair, Wilfred A van der Donk
Lantibiotics are ribosomally synthesized and post-translationally modified antimicrobial peptides containing thioether rings. In addition to these cross-links, the clinical candidate lantibiotic NAI-107 also possesses a C-terminal S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) and a unique 5-chloro-l-tryptophan (ClTrp) moiety linked to its potent bioactivity. Bioinformatic and genetic analyses on the NAI-107 biosynthetic gene cluster identified mibH and mibD as genes encoding flavoenzymes responsible for the formation of ClTrp and AviCys, respectively...
February 17, 2017: ACS Chemical Biology
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