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uridine monophosphate

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https://www.readbyqxmd.com/read/28835346/the-discovery-of-idx21437-design-synthesis-and-antiviral-evaluation-of-2-%C3%AE-chloro-2-%C3%AE-c-methyl-branched-uridine-pronucleotides-as-potent-liver-targeted-hcv-polymerase-inhibitors
#1
François-René Alexandre, Eric Badaroux, John P Bilello, Stéphanie Bot, Tony Bouisset, Guillaume Brandt, Sylvie Cappelle, Christopher Chapron, Dominique Chaves, Thierry Convard, Clément Counor, Daniel Da Costa, David Dukhan, Marion Gay, Gilles Gosselin, Jean-François Griffon, Kusum Gupta, Brenda Hernandez-Santiago, Massimiliano La Colla, Marie-Pierre Lioure, Julien Milhau, Jean-Laurent Paparin, Jérôme Peyronnet, Christophe Parsy, Claire Pierra Rouvière, Houcine Rahali, Rachid Rahali, Aurélien Salanson, Maria Seifer, Ilaria Serra, David Standring, Dominique Surleraux, Cyril B Dousson
Herein we describe the discovery of IDX21437 35b, a novel RPd-aminoacid-based phosphoramidate prodrug of 2'-α-chloro-2'-β-C-methyluridine monophosphate. Its corresponding triphosphate 6 is a potent inhibitor of the HCV NS5B RNA-dependent RNA polymerase (RdRp). Despite showing very weak activity in the in vitro Huh-7 cell based HCV replicon assay, 35b demonstrated high levels of active triphosphate 6 in mouse liver and human hepatocytes. A biochemical study revealed that the metabolism of 35b was mainly attributed to carboxyesterase 1 (CES1), an enzyme which is underexpressed in HCV Huh-7-derived replicon cells...
September 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28762967/multi-temperature-study-of-potassium-uridine-5-monophosphate-electron-density-distribution-and-anharmonic-motion-modelling
#2
Katarzyna N Jarzembska, Katarzyna Řlepokura, Radosław Kamiński, Matthias J Gutmann, Paulina M Dominiak, Krzysztof Woźniak
Uridine, a nucleoside formed of a uracil fragment attached to a ribose ring via a β-N1-glycosidic bond, is one of the four basic components of ribonucleic acid. Here a new anhydrous structure and experimental charge density distribution analysis of a uridine-5'-monophosphate potassium salt, K(UMPH), is reported. The studied case constitutes the very first structure of a 5'-nucleotide potassium salt according to the Cambridge Structural Database. The excellent crystal quality allowed the collection of charge density data at various temperatures, i...
August 1, 2017: Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials
https://www.readbyqxmd.com/read/28713420/modeling-the-metabolism-of-arabidopsis-thaliana-application-of-network-decomposition-and-network-reduction-in-the-context-of-petri-nets
#3
Ina Koch, Joachim Nöthen, Enrico Schleiff
Motivation:Arabidopsis thaliana is a well-established model system for the analysis of the basic physiological and metabolic pathways of plants. Nevertheless, the system is not yet fully understood, although many mechanisms are described, and information for many processes exists. However, the combination and interpretation of the large amount of biological data remain a big challenge, not only because data sets for metabolic paths are still incomplete. Moreover, they are often inconsistent, because they are coming from different experiments of various scales, regarding, for example, accuracy and/or significance...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28559281/uridine-monophosphate-synthetase-enables-eukaryotic-de-novo-nad-biosynthesis-from-quinolinic-acid
#4
Melanie R McReynolds, Wenqing Wang, Lauren M Holleran, Wendy Hanna-Rose
NAD(+) biosynthesis is an attractive and promising therapeutic target for influencing health span and obesity-related phenotypes as well as tumor growth. Full and effective use of this target for therapeutic benefit requires a complete understanding of NAD(+) biosynthetic pathways. Here, we report a previously unrecognized role for a conserved phosphoribosyltransferase in NAD(+) biosynthesis. Because a required quinolinic acid phosphoribosyltransferase (QPRTase) is not encoded in its genome, Caenorhabditis elegans are reported to lack a de novo NAD(+) biosynthetic pathway...
July 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28542039/role-of-the-uridine-cytidine-kinase-2-mutation-in-cellular-sensitiveness-toward-3-ethynylcytidine-treatment-of-human-cancer-cells
#5
Akira Sato, Takeshi Takano, Akiko Hiramoto, Tomoharu Naito, Akira Matsuda, Masakazu Fukushima, Yusuke Wataya, Hye-Sook Kim
A nucleosidic medicine, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine [3'-ethynylcytidine (ECyd)], is a potent inhibitor of RNA polymerase I and shows anticancer activity to various human solid tumors in vitro and in vivo. ECyd is phosphorylated to 3'-ethyntlcytidine 5'-monophosphate by uridine/cytidine kinase 2 (UCK2) and subsequently further to diphosphate and triphosphate (3'-ethyntlcytidine 5'-diphosphate, 3'-ethyntlcytidine 5'-triphosphate). 3'-Ethyntlcytidine 5'-triphosphate is an active metabolite that can inhibit RNA polymerase I competitively, causing cancer cell death...
August 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28520982/genome-wide-mrna-processing-in-methanogenic-archaea-reveals-post-transcriptional-regulation-of-ribosomal-protein-synthesis
#6
Lei Qi, Lei Yue, Deqin Feng, Fengxia Qi, Jie Li, Xiuzhu Dong
Unlike stable RNAs that require processing for maturation, prokaryotic cellular mRNAs generally follow an 'all-or-none' pattern. Herein, we used a 5΄ monophosphate transcript sequencing (5΄P-seq) that specifically captured the 5΄-end of processed transcripts and mapped the genome-wide RNA processing sites (PSSs) in a methanogenic archaeon. Following statistical analysis and stringent filtration, we identified 1429 PSSs, among which 23.5% and 5.4% were located in 5΄ untranslated region (uPSS) and intergenic region (iPSS), respectively...
July 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28472077/improvement-of-uridine-production-of-bacillus-subtilis-by-atmospheric-and-room-temperature-plasma-mutagenesis-and-high-throughput-screening
#7
Xiaoguang Fan, Heyun Wu, Guoliang Li, Hui Yuan, Hongchao Zhang, Yanjun Li, Xixian Xie, Ning Chen
In the present study, a novel breeding strategy of atmospheric and room temperature plasma (ARTP) mutagenesis was used to improve the uridine production of engineered Bacillus subtilis TD12np. A high-throughput screening method was established using both resistant plates and 96-well microplates to select the ideal mutants with diverse phenotypes. Mutant F126 accumulated 5.7 and 30.3 g/L uridine after 30 h in shake-flask and 48 h in fed-batch fermentation, respectively, which represented a 4.4- and 8.7-fold increase over the parent strain...
2017: PloS One
https://www.readbyqxmd.com/read/28451191/construction-of-an-octosyl-acid-backbone-catalyzed-by-a-radical-s-adenosylmethionine-enzyme-and-a-phosphatase-in-the-biosynthesis-of-high-carbon-sugar-nucleoside-antibiotics
#8
Nisha He, Pan Wu, Yongxing Lei, Baofu Xu, Xiaochen Zhu, Gudan Xu, Yaojie Gao, Jianzhao Qi, Zixin Deng, Gongli Tang, Wenqing Chen, Youli Xiao
Unique bicyclic octosyl uronic acid nucleosides include ezomycin, malayamycin, and octosyl acid (OA). They are structurally characterized by OA, an unusual 8-carbon furanosyl nucleoside core proposed to be the precursor to polyoxin and nikkomycin. Despite the well-known bioactivity of these nucleoside antibiotics, the biosynthesis of OA has not been elucidated yet. Here we report the two pivotal enzymatic steps in the polyoxin biosynthetic pathway leading to the identification of OA as a key intermediate. Our data suggest that this intermediate is formed via a free radical reaction catalyzed by the radical S-adenosylmethionine (SAM) enzyme, PolH, and using 3'-enolpyruvyl uridine 5'-monophosphate (3'-EUMP) as a substrate...
January 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28393936/effect-of-counterions-on-the-micellization-and-monolayer-behaviour-of-cationic-gemini-surfactants
#9
M S Islam, S M Shortall, G M Mekhail, S P Callender, O Madkhali, Z Bharwani, D Ayyash, K Kobernyk, S D Wettig
The effect of various inorganic and organic counterions on the aggregation behavior of gemini surfactants was examined to investigate the dominant influence of the anions on their micellization and aggregation behavior. This study included eight ethanediyl-α,ω-bis-(dimethylhexadecylammonium) gemini surfactants (GS, also known as 16-2-16) having counterions of chloride (Cl(-)), bromide (Br(-)), malate, tartrate, adenosine monophosphate (AMP), guanosine monophosphate (GMP), cytidine monophosphate (CMP), and uridine monophosphate (UMP)...
May 3, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28388410/physiologic-medium-rewires-cellular-metabolism-and-reveals-uric-acid-as-an-endogenous-inhibitor-of-ump-synthase
#10
Jason R Cantor, Monther Abu-Remaileh, Naama Kanarek, Elizaveta Freinkman, Xin Gao, Abner Louissaint, Caroline A Lewis, David M Sabatini
A complex interplay of environmental factors impacts the metabolism of human cells, but neither traditional culture media nor mouse plasma mimic the metabolite composition of human plasma. Here, we developed a culture medium with polar metabolite concentrations comparable to those of human plasma (human plasma-like medium [HPLM]). Culture in HPLM, relative to that in traditional media, had widespread effects on cellular metabolism, including on the metabolome, redox state, and glucose utilization. Among the most prominent was an inhibition of de novo pyrimidine synthesis-an effect traced to uric acid, which is 10-fold higher in the blood of humans than of mice and other non-primates...
April 6, 2017: Cell
https://www.readbyqxmd.com/read/28347333/a-phase-ii-study-of-preoperative-chemoradiation-with-tegafur-uracil-plus-leucovorin-for-locally-advanced-rectal-cancer-with-pharmacogenetic-analysis
#11
Sun Young Kim, Ji Yeon Baek, Jae Hwan Oh, Sung Chan Park, Dae Kyung Sohn, Min Ju Kim, Hee Jin Chang, Sun-Young Kong, Dae Yong Kim
BACKGROUND: This study aimed to evaluate the efficacy of a high dose of oral tegafur-uracil (400 mg/m(2)) plus leucovorin with preoperative chemoradiation of locally advanced rectal cancer and to explore the impact of polymorphisms of cytochrome P 2A6 (CYP2A6), uridine monophosphate synthetase (UMPS), and ATP-binding cassette B1 (ABCB1) on clinical outcome. METHODS: Patients with cT3 or cT4 rectal cancer were enrolled and were given tegafur-uracil 400 mg/m(2)/day and leucovorin 90 mg/m(2)/day for 7 days a week during preoperative chemoradiation (50...
March 27, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28336748/the-sweet-side-of-ampk-signaling-regulation-of-gfat1
#12
John W Scott, Jonathan S Oakhill
Maintaining a steady balance between nutrient supply and energy demand is essential for all living organisms and is achieved through the dynamic control of metabolic processes that produce and consume adenosine-5'-triphosphate (ATP), the universal currency of energy in all cells. A key sensor of cellular energy is the adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), which is the core component of a signaling network that regulates energy and nutrient metabolism. AMPK is activated by metabolic stresses that decrease cellular ATP, and functions to restore energy balance by orchestrating a switch in metabolism away from anabolic pathways toward energy-generating catabolic processes...
March 23, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28303227/analysis-of-cordyceps-by-multi-column-liquid-chromatography
#13
Zhengming Qian, Shaoping Li
Cordyceps is a famous traditional Chinese medicine (TCM) that has been used in China for hundreds of years. In the present study a multi-column liquid chromatography (MC-LC) system was developed for the qualitative analysis of macromolecules and micromolecules in Cordyceps. The MC-LC system includes a size exclusion pre-column, a size exclusion column (SEC) and a reversed phase column (RP) which were controlled by column-switching valves. The sample was separated by the size exclusion pre-column into two fractions (macromolecules and micromolecules)...
March 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28243144/a-double-blind-randomized-comparative-study-of-the-use-of-a-combination-of-uridine-triphosphate-trisodium-cytidine-monophosphate-disodium-and-hydroxocobalamin-versus-isolated-treatment-with-hydroxocobalamin-in-patients-presenting-with-compressive-neuralgias
#14
Henrique Goldberg, Marco Antonio Mibielli, Carlos Pereira Nunes, Stephanie Wrobel Goldberg, Luiz Buchman, Spyros Ge Mezitis, Helio Rzetelna, Lisa Oliveira, Mauro Geller, Fernanda Wajnsztajn
CONTEXT: This paper reports on the results of treatment of compressive neuralgia using a combination of nucleotides (uridine triphosphate trisodium [UTP] and cytidine monophosphate disodium [CMP]) and vitamin B12. OBJECTIVES: To assess the safety and efficacy of the combination of nucleotides (UTP and CMP) and vitamin B12 in patients presenting with neuralgia arising from neural compression associated with degenerative orthopedic alterations and trauma, and to compare these effects with isolated administration of vitamin B12...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28222577/acute-ingestion-of-neuromuscular-enhancement-supplements-do-not-improve-power-output-work-capacity-and-cognition
#15
Jennifer A Bunn, Andrew Crossley, Morgan D Timiney
BACKGROUND: Improving motor unit recruitment and function is trainable and positively affects performance. Evidence suggests that supplementation of choline, uridine, and docosahexaenoic acid (DHA) may also enhance neuromuscular function. The purpose of this study was to assess the influence of acute ingestion of these supplements on anaerobic exercise performance and cognition. METHODS: Twenty college-aged trained males (21.2 ± 1.4 years, 181.2 ± 6.1 cm, 94.4 ± 20...
February 21, 2017: Journal of Sports Medicine and Physical Fitness
https://www.readbyqxmd.com/read/28205048/mild-orotic-aciduria-in-umps-heterozygotes-a-metabolic-finding-without-clinical-consequences
#16
Saskia B Wortmann, Margaret A Chen, Roberto Colombo, Alessandro Pontoglio, Bader Alhaddad, Lorenzo D Botto, Tatiana Yuzyuk, Curtis R Coughlin, Maria Descartes, Stephanie Grűnewald, Bruno Maranda, Philippa B Mills, James Pitt, Catherine Potente, Richard Rodenburg, Leo A J Kluijtmans, Srirangan Sampath, Emil F Pai, Ron A Wevers, George E Tiller
BACKGROUND: Elevated urinary excretion of orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with orotic aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary orotic aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life...
May 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28187683/proteomics-profiling-of-chimeric-truncated-tissue-plasminogen-activator-producing-chinese-hamster-ovary-cells-cultivated-in-a-chemically-defined-medium-supplemented-with-protein-hydrolysates
#17
Bahareh Azarian, Seyedeh Matin Sajedin, Amin Azimi, Mozhgan Raigani, Behrouz Vaziri, Fatemeh Davami
Background: Culture media enrichment through the addition of protein hydrolysates is beneficial for achieving higher protein expression. Methods: In this study, designing the optimum mixture of four soy and casein-derived hydrolysates was successfully performed by design of experiment and specific productivity increased in all predicted combinations. Protein profile of recombinant CHO (rCHO) cells producing tissue plasminogen activator in a serum-free medium (SFM) supplemented with designed hydrolysate additives was compared to that of rCHO cells cultivated in SFM...
May 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28181004/mass-spectrometric-analysis-of-non-canonical-cyclic-nucleotides
#18
Heike Bähre, Volkhard Kaever
Contemporary investigations regarding the (patho)physiological roles of the non-canonical cyclic nucleoside monophosphates (cNMP) cytidine 3',5'-cyclic monophosphate (cCMP) and uridine 3',5'-cyclic monophosphate (cUMP) have been hampered by the lack of highly specific and sensitive analytic methods for these analytes. In addition, the existence of 2',3'-cNMP besides 3',5'-cNMP has been described recently. HPLC coupled with tandem mass spectrometry (HPLC-MS/MS) is the method of choice for identification and quantification of low-molecular weight endogenous metabolites...
2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28160163/nucleotide-selectivity-in-abiotic-rna-polymerization-reactions
#19
Kristin M Coari, Rebecca C Martin, Kopal Jain, Linda B McGown
In order to establish an RNA world on early Earth, the nucleotides must form polymers through chemical rather than biochemical reactions. The polymerization products must be long enough to perform catalytic functions, including self-replication, and to preserve genetic information. These functions depend not only on the length of the polymers, but also on their sequences. To date, studies of abiotic RNA polymerization generally have focused on routes to polymerization of a single nucleotide and lengths of the homopolymer products...
February 3, 2017: Origins of Life and Evolution of the Biosphere
https://www.readbyqxmd.com/read/28130366/analysis-of-uracil-phosphoribosyltransferase-expression-in-mycobacterium-tuberculosis-and-evaluation-of-upp-knockout-strain-in-infected-mice
#20
Anne Drumond Villela, Ha Pham, Victoria Jones, Anna E Grzegorzewicz, Valnês da Silva Rodrigues-Junior, Maria Martha Campos, Luiz Augusto Basso, Mary Jackson, Diógenes Santiago Santos
The upp (Rv3309c)-encoded uracil phosphoribosyltransferase from Mycobacterium tuberculosis (MtUPRT) converts uracil and 5-phosphoribosyl-α-1-pyrophosphate into pyrophosphate and uridine 5΄-monophosphate, the precursor of all pyrimidine nucleotides. A M. tuberculosis knockout strain for upp gene was generated by allelic replacement. Knockout and complemented strains were validated by a functional assay of uracil incorporation. A basal level of MtUPRT expression is shown to be independent of either growth medium used, addition of bases, or oxygen presence/absence...
February 1, 2017: FEMS Microbiology Letters
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