Academic literature on the topic 'Synthesis of pyrimidine nucleotides'

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Journal articles on the topic "Synthesis of pyrimidine nucleotides"

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Weetall, Marla, Kensuke Kojima, Sujan Piya, Christopher Trotta, John Baird, Kylie O'Keefe, Bansri Furia, Gautam M. Borthakur, and Robert Spiegel. "Inhibition of De Novo Pyrimidine Nucleotide Synthesis By the Novel DHODH Inhibitor PTC299 Induces Differentiation and/or Death of AML Cells." Blood 134, Supplement_1 (November 13, 2019): 5152. http://dx.doi.org/10.1182/blood-2019-124569.

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Background: Pyrimidine nucleotides are generated either by de novo synthesis or the salvage pathway in which pyrimidine nucleotides are obtained from the diet. Resting cells typically acquire adequate pyrimidine nucleotides from the salvage pathway. Rapidly proliferating cells, however, are dependent on the de novo synthesis of pyrimidine nucleotides. PTC299 is an inhibitor of dihydroorotate dehydrogenase (DHODH), a rate limiting enzyme for de novo pyrimidine nucleotide synthesis that had previously been in clinical trials for treatment of solid tumors. Results: Using 15N-labelled glutamine, we show that PTC299 reduces de novo pyrimidine nucleotide synthesis in PTC299-sensitive AML cell lines resulting in a depletion of total pyrimidine nucleotides. In parallel to reduction in pyrimidine nucleotides, PTC 299 leads to accumulation of DHO, the substrate of DHODH and unexpectedly, an accumulation of N-carbamoyl aspartate the metabolite above DHO in the de novo pyrimidine nucleotide synthesis pathway. PTC299 was broadly active against leukemia and lymphoma lines, with 80% of the AML lines tested showing sensitivity. Treatment of AML cell lines with PTC299 induced differentiation as shown by increased CD14 and/or reduced proliferation. Using isogenic AML lines, we show that PTC299 reduces the proliferation of both p53 wildtype and p53 deficient leukemia calls with similar potency as measured by the concentration of PTC299 required to reduce cell number by 50% (CC50). In cells expressing wildtype p53, PTC299 increases p53 activation. However, p53- wildtype cells undergo increased apoptosis whereas p53-deficience cells undergo necrosis. PTC299 induced a G1/S cell cycle arrest, also independent of p53 status. PTC299 increased H2A.X (a marker of double stranded DNA breaks) in both p53 wildtype and p53 deficient cells. These data suggest that the depletion of nucleotides results in stalling at the replication fork, and subsequent DNA-breaks. Conclusion: De novo pyrimidine nucleotide synthesis is critical for AML survival and proliferation. Depletion of nucleotides results in reduced proliferation, triggering either differentiation and/or cell death. Disclosures Weetall: PTC Therapeutics: Employment. Trotta:PTC Therapeutics: Employment. Baird:PTC Therapeutics: Employment. O'Keefe:PTC Therapeutics: Employment. Furia:PTC Therapeutics: Employment. Borthakur:PTC Therapeutics: Consultancy; Janssen: Research Funding; AbbVie: Research Funding; Argenx: Membership on an entity's Board of Directors or advisory committees; NKarta: Consultancy; AstraZeneca: Research Funding; Xbiotech USA: Research Funding; Incyte: Research Funding; GSK: Research Funding; Oncoceutics, Inc.: Research Funding; Novartis: Research Funding; Agensys: Research Funding; BMS: Research Funding; Oncoceutics: Research Funding; Cantargia AB: Research Funding; Bayer Healthcare AG: Research Funding; Eisai: Research Funding; FTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; BioTheryX: Membership on an entity's Board of Directors or advisory committees; Polaris: Research Funding; Merck: Research Funding; Cyclacel: Research Funding; Eli Lilly and Co.: Research Funding; BioLine Rx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Arvinas: Research Funding; Tetralogic Pharmaceuticals: Research Funding; Strategia Therapeutics: Research Funding. Spiegel:PTC Therapeutics: Consultancy.
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Szondy, Z., and E. A. Newsholme. "The effect of glutamine concentration on the activity of carbamoyl-phosphate synthase II and on the incorporation of [3H]thymidine into DNA in rat mesenteric lymphocytes stimulated by phytohaemagglutinin." Biochemical Journal 261, no. 3 (August 1, 1989): 979–83. http://dx.doi.org/10.1042/bj2610979.

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The maximum catalytic activities of carbamoyl-phosphate synthase II, a limiting enzyme for pyrimidine nucleotide synthesis, are very much less than those of glutaminase, a limiting enzyme for glutamine utilization, in lymphocytes and macrophages; and the flux through the pathway for pyrimidine formation de novo is only about 0.4% of the rate of glutamine utilization by lymphocytes. The Km of synthase II for glutamine is about 16 microM and the concentration of glutamine necessary to stimulate lymphocyte proliferation half-maximally is about 21 microM. This agreement suggests that the importance of glutamine for these cells is provision of nitrogen for biosynthesis of pyrimidine nucleotides (and probably purine nucleotides). However, the glutamine concentration necessary for half-maximal stimulation of glutamine utilization (glutaminolysis) by the lymphocytes is 2.5 mM. The fact that the rate of glutamine utilization by lymphocytes is markedly in excess of the rate of the pathway for pyrimidine nucleotide synthesis de novo and that the Km and ‘half-maximal concentration’ values are so different, suggests that the glutaminolytic pathway is independent of the use of glutamine nitrogen for pyrimidine synthesis.
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West, Thomas P. "Pyrimidine nucleotide synthesis inPseudomonascitronellolis." Canadian Journal of Microbiology 50, no. 6 (June 1, 2004): 455–59. http://dx.doi.org/10.1139/w04-028.

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Pyrimidine biosynthesis was active in Pseudomonas citronellolis ATCC 13674 and appeared to be regulated by pyrimidines. When wild-type cells were grown on succinate in the presence of uracil, the de novo enzyme activities were depressed while only four enzyme activities were depressed in the glucose-grown cells. On either carbon source, orotic acid-grown cells had diminished aspartate transcarbamoylase, dihydroorotase or OMP decarboxylase activity. Pyrimidine limitation of glucose-grown pyrimidine auxotrophic cells resulted in de novo enzyme activities, except for transcarbamoyolase activity, that were elevated by more than 5-fold compared to their activities in uracil-grown cells. Since pyrimidine limitation of succinate-grown mutant cells produced less enzyme derepression, catabolite repression appeared to be a factor. At the level of enzyme activity, aspartate transcarbamoylase activity in P. citronellolis was strongly inhibited by all effectors tested. Compared to the regulation of pyrimidine biosynthesis in taxonomically-related species, pyrimidine biosynthesis in P. citronellolis appeared more highly regulated.Key words: pyrimidine biosynthesis, regulation, Pseudomonas citronellolis, auxotroph, aspartate transcarbamoylase, inhibition.
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Shanmugasundaram, Muthian, Annamalai Senthilvelan, and Anilkumar R. Kore. "C-5 Substituted Pyrimidine Nucleotides/Nucleosides: Recent Progress in Synthesis, Functionalization, and Applications." Current Organic Chemistry 23, no. 13 (October 9, 2019): 1439–68. http://dx.doi.org/10.2174/1385272823666190809124310.

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The chemistry of C5 substituted pyrimidine nucleotide serves as a versatile molecular biology probe for the incorporation of DNA/RNA that has been involved in various molecular biology applications such as gene expression, chromosome, and mRNA fluorescence in situ hybridization (FISH) experiment, mutation detection on arrays and microarrays, in situ RT-PCR, and PCR. In addition to C5 substituted pyrimidine nucleotide, C5 substituted pyrimidine nucleoside displays a broad spectrum of biological applications such as antibacterial, antiviral and anticancer activities. This review focusses on the recent development in the synthesis of aminoallyl pyrimidine nucleotide, aminopropargyl pyrimidine nucleotide, fluorescent probes containing C5 substituted pyrimidine nucleotide, 2′-deoxycytidine nucleoside containing vinylsulfonamide and acrylamide modification, C5 alkenyl, C5 alkynyl, and C5 aryl pyrimidine nucleosides through palladium-catalyzed reaction, pyrimidine nucleoside containing triazole moiety through Click reaction, 5-isoxazol-3-yl-pyrimidine nucleoside, C5 azide modified pyrimidine nucleoside, 2′-deoxycytidine nucleotide containing photocleavable moiety, and uridine nucleoside containing germane and their biological applications are outlined.
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Hassan, Mohamed E. "Photochemical synthesis of C(5) alkyl and heteroaryl substituted pyrimidine nucleotides." Collection of Czechoslovak Chemical Communications 50, no. 10 (1985): 2319–23. http://dx.doi.org/10.1135/cccc19852319.

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A simple and direct method for the synthesis of C-5 modified nucleosides is described. Photoirradiation of 2'-deoxyuridine 5'-phosphate (I), in the presence of haloheteroarenes afforded the C-5 heteroaryl substituted nucleotides. 5-(2-Hydroxyethyl)nucleotide also obtained from photocoupling of I with 2-iodoethanol. Photoirradiation of 5-iodo-2-deoxyuridine 5'-phosphate (II), in the presence of methyl acrylate or acrylonitrile, gave 5-(2-methoxycarbonylethenyl) and 5-(2-cyanoethenyl) nucleotide, respectively.
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Froschauer, Elisabeth M., Nicole Rietzschel, Melanie R. Hassler, Markus Binder, Rudolf J. Schweyen, Roland Lill, Ulrich Mühlenhoff, and Gerlinde Wiesenberger. "The mitochondrial carrier Rim2 co-imports pyrimidine nucleotides and iron." Biochemical Journal 455, no. 1 (September 13, 2013): 57–65. http://dx.doi.org/10.1042/bj20130144.

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Mitochondrial iron uptake is of key importance both for organelle function and cellular iron homoeostasis. The mitochondrial carrier family members Mrs3 and Mrs4 (homologues of vertebrate mitoferrin) function in organellar iron supply, yet other low efficiency transporters may exist. In Saccharomyces cerevisiae, overexpression of RIM2 (MRS12) encoding a mitochondrial pyrimidine nucleotide transporter can overcome the iron-related phenotypes of strains lacking both MRS3 and MRS4. In the present study we show by in vitro transport studies that Rim2 mediates the transport of iron and other divalent metal ions across the mitochondrial inner membrane in a pyrimidine nucleotide-dependent fashion. Mutations in the proposed substrate-binding site of Rim2 prevent both pyrimidine nucleotide and divalent ion transport. These results document that Rim2 catalyses the co-import of pyrimidine nucleotides and divalent metal ions including ferrous iron. The deletion of RIM2 alone has no significant effect on mitochondrial iron supply, Fe–S protein maturation and haem synthesis. However, RIM2 deletion in mrs3/4Δ cells aggravates their Fe–S protein maturation defect. We conclude that under normal physiological conditions Rim2 does not play a significant role in mitochondrial iron acquisition, yet, in the absence of the main iron transporters Mrs3 and Mrs4, this carrier can supply the mitochondrial matrix with iron in a pyrimidine-nucleotide-dependent fashion.
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Sprenger, Hans-Georg, Thomas MacVicar, Amir Bahat, Kai Uwe Fiedler, Steffen Hermans, Denise Ehrentraut, Katharina Ried, et al. "Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity." Nature Metabolism 3, no. 5 (April 26, 2021): 636–50. http://dx.doi.org/10.1038/s42255-021-00385-9.

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AbstractCytosolic mitochondrial DNA (mtDNA) elicits a type I interferon response, but signals triggering the release of mtDNA from mitochondria remain enigmatic. Here, we show that mtDNA-dependent immune signalling via the cyclic GMP–AMP synthase‒stimulator of interferon genes‒TANK-binding kinase 1 (cGAS–STING–TBK1) pathway is under metabolic control and is induced by cellular pyrimidine deficiency. The mitochondrial protease YME1L preserves pyrimidine pools by supporting de novo nucleotide synthesis and by proteolysis of the pyrimidine nucleotide carrier SLC25A33. Deficiency of YME1L causes inflammation in mouse retinas and in cultured cells. It drives the release of mtDNA and a cGAS–STING–TBK1-dependent inflammatory response, which requires SLC25A33 and is suppressed upon replenishment of cellular pyrimidine pools. Overexpression of SLC25A33 is sufficient to induce immune signalling by mtDNA. Similarly, depletion of cytosolic nucleotides upon inhibition of de novo pyrimidine synthesis triggers mtDNA-dependent immune responses in wild-type cells. Our results thus identify mtDNA release and innate immune signalling as a metabolic response to cellular pyrimidine deficiencies.
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Chunduru, Jayendra, and Thomas P. West. "Pyrimidine nucleotide synthesis in the emerging pathogen Pseudomonas monteilii." Canadian Journal of Microbiology 64, no. 6 (June 2018): 432–38. http://dx.doi.org/10.1139/cjm-2018-0015.

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Regulation of pyrimidine biosynthesis by pyrimidines in the emerging, opportunistic human pathogen Pseudomonas monteilii ATCC 700476 was evident. When wild-type cells were grown on succinate in the presence of uracil or orotic acid, the activities of all 5 pyrimidine biosynthetic enzymes were depressed while the activities of 3 of the enzymes decreased in glucose-grown cells supplemented with uracil or orotic acid compared with unsupplemented cells. Pyrimidine limitation of succinate- or glucose-grown pyrimidine auxotrophic cells lacking orotate phosphoribosyltransferase activity resulted in more than a doubling of the pyrimidine biosynthetic enzyme activities relative to their activities in uracil-grown cells. Independent of carbon source, pyrimidine-limited cells of the pyrimidine auxotrophic cells deficient for dihydroorotase activity generally resulted in a slight elevation or depression of the pyrimidine biosynthetic enzyme activities compared with their activities in cells grown under saturating uracil conditions. Aspartate transcarbamoylase activity in P. monteilii was regulated at the enzyme activity level, since the enzyme was strongly inhibited by CTP, UMP, GMP, GDP, ADP, and UTP. In summary, the regulation of pyrimidine biosynthesis in P. monteilii could be used to control its growth or to differentiate it biochemically from other related species of Pseudomonas.
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Deval, Jérôme, Megan H. Powdrill, Claudia M. D'Abramo, Luciano Cellai, and Matthias Götte. "Pyrophosphorolytic Excision of Nonobligate Chain Terminators by Hepatitis C Virus NS5B Polymerase." Antimicrobial Agents and Chemotherapy 51, no. 8 (May 14, 2007): 2920–28. http://dx.doi.org/10.1128/aac.00186-07.

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ABSTRACT Nonobligate chain terminators, such as 2′-C-methylated nucleotides, block RNA synthesis by the RNA-dependent RNA polymerase (RdRp) of hepatitis C virus (HCV). Previous studies with related viral polymerases have shown that classical chain terminators lacking the 3′-hydroxyl group can be excised in the presence of pyrophosphate (PPi), which is detrimental to the inhibitory activity of these compounds. Here we demonstrate that the HCV RdRp enzyme is capable of removing both obligate and clinically relevant nonobligate chain terminators. Pyrimidines are more efficiently excised than are purines. The presence of the next complementary templated nucleotide literally blocks the excision of obligate chain terminators through the formation of a dead-end complex (DEC). However, 2′-C-methylated CMP is still cleaved efficiently under these conditions. These findings show that a 2′-methylated primer terminus impedes nucleotide binding. The S282T mutation, associated with resistance to 2′-C-methylated nucleotides, does not affect the excision patterns. Thus, the decreased susceptibility to 2′-C-methylated nucleotides appears to be based solely on improved discrimination between the inhibitor and its natural counterpart. In conclusion, our data suggest that the phosphorolytic excision of nonobligate, pyrimidine-based chain terminators can diminish their potency. The templated nucleotide does not appear to provide protection from excision through DEC formation.
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Pels Rijcken, W. R., G. J. M. Hooghwinkel, and W. Ferwerda. "Pyrimidine metabolism and sugar nucleotide synthesis in rat liver." Biochemical Journal 266, no. 3 (March 15, 1990): 777–83. http://dx.doi.org/10.1042/bj2660777.

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With radioactive precursors, the labelling kinetics of the soluble pyrimidine nucleotides and of RNA were measured in rat liver to determine the contribution of the metabolic flows through synthesis de novo and the salvage pathway. To separate and quantify all pyrimidine nucleotides, an h.p.l.c. technique was developed using anion-exchange chromatography and reversed-phase chromatography. The concentrations of cytidine nucleotides were in the range of 30-45 nmol/g wet weight, and the concentrations of the uridine phosphates and of the UDP-sugars were approx. 6 and 20 times higher respectively. After a single injection of [14C]orotic acid and of [3H]cytidine, the specific radioactivities were determined as a function of time. The 14C/3H ratio was calculated and gave a good indication of the involvement of the different flows. It could be concluded that UTP derived from synthesis de novo and from the salvage pathway is not completely mixed before being utilized. The flow of the salvage pathway is relatively more directed to RNA synthesis in the nucleus and that of synthesis de novo to cytoplasmic processes. For CTP it could also be concluded that the flow of the salvage pathway was relatively more directed to RNA synthesis in the nucleus. Because of the nuclear localization of the enzyme CMP-NeuAc (N-acetylneuraminate) synthase, special attention was paid to CMP-NeuAc. However, a conclusion about a location about the synthesis of CMP-NeuAc could not unequivocally be drawn, because of the small differences in 14C/3H ratio and the different values for the CDP-lipids.
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Dissertations / Theses on the topic "Synthesis of pyrimidine nucleotides"

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蘇雅頌 and Ngar-chung Nellie So. "Pyrimidine nucleotide biosynthesis in adult angiostrongylus Cantonensis (Nematoda : Metastrongyloidea)." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1993. http://hub.hku.hk/bib/B3123320X.

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Bean, Heather D. "Prebiotic synthesis of nucleic acids." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/28259.

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Thesis (M. S.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2008.
Committee Chair: Hud, Nicholas V.; Committee Member: Fox, Ronald F.; Committee Member: Lynn, David G.; Committee Member: Powers, James C.; Committee Member: Wartell, Roger M.; Committee Member: Williams, Loren D.
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Rayala, Ramanjaneyulu. "Design and Synthesis of Novel Nucleoside Analogues: Oxidative and Reductive Approaches toward Synthesis of 2'-Fluoro Pyrimidine Nucleosides." FIU Digital Commons, 2015. http://digitalcommons.fiu.edu/etd/2172.

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Fluorinated nucleosides, especially the analogues with fluorine atom(s) in the ribose ring, have been known to exert potent biological activities. The first part of this dissertation was aimed at developing oxidative desulfurization-fluorination and reductive desulfonylation-fluorination methodologies toward the synthesis of 2'-mono and/or 2',2'-difluoro pyrimidine nucleosides from the corresponding 2'-arylthiopyrimidine precursors. Novel oxidative desulfurization-difluorination methodology was developed for the synthesis of α,α-difluorinted esters from the corresponding α-arylthio esters, wherein the arylthio group is present on a secondary internal carbon. For the reductive desulfonylation studies, cyclic voltammetry was utilized to measure the reduction potentials at which the sulfone moiety of substrates can be cleaved. The 5-bromo pyrimidine nucleosides and 8-bromo purine nucleosides act as crucial intermediates in various synthetic transformations. The second part of the present dissertation was designed to develop a novel bromination methodology using 1,3-dibromo-5,5-dimethylhydantoin (DBH). Various protected and deprotected pyrimidine and purine nucleosides were converted to their respective C5 and C8 brominated counterparts using DBH. The effect of Lewis acids, solvents, and temperature on the efficiency of bromination was studied. Also, N-bromosuccinimide (NBS) or DBH offered a convenient access to 8-bromotoyocamycin and 8-bromosangivamycin. Third part of this research work focuses on the design and synthesis of 6-N-benzylated derivatives of 7-deazapurine nucleoside antibiotics, such as tubercidin, sangivamycin and toyocamycin. Target molecules were synthesized by two methods. First method involves treatment of 7-deazapurine substrates with benzylbromide followed by dimethylamine-promoted Dimroth rearrangement. The second method employs fluoro-diazotization followed by SNAr displacement of the 6-fluoro group by a benzylamine. The 6-N-benzylated 7-deazapurine nucleosides showed type-specific inhibition of cancer cell proliferation at micromolar concentrations and weak inhibition of human equilibrative nucleoside transport protein (hENT1). In the fourth part of this dissertation, syntheses of C7 or C8 modified 7-deazapurine nucleosides, which might exhibit fluorescent properties, were undertaken. 8-Azidotoyocamycin was synthesized by treatment of 8-bromotoyocamycin with sodium azide. Strain promoted click chemistry of 8-azidotoyocamycin with cyclooctynes gave the corresponding 8-triazolyl derivatives. Alternatively, 7-benzotriazolyl tubercidin was synthesized by iodine catalyzed CH arylation of tubercidin with benzotriazole.
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Barbosa, Sara Isabel Cadinha. "Compostos que interferem no metabolismo dos purina- e pirimidina-nucleótidos: utilização como agentes terapêuticos." Master's thesis, [s.n.], 2015. http://hdl.handle.net/10284/5160.

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
O conteúdo deste trabalho será desenvolvido em dois temas principais, um referente à utilização de compostos que interferem no metabolismo dos purina- e pirimidinanucleótidos como agentes antineoplásicos e outro referente à sua utilização como agentes antivirais. A síntese dos nucleótidos envolve a construção de ácidos nucleicos e a inserção dos derivados de nucleótidos noutras vias bioquímicas, sendo responsável por inúmeras funções do metabolismo celular. Existem patologias que envolvem enzimas essenciais do metabolismo dos nucleótidos, o que levou à síntese de novos fármacos. As doenças oncológicas continuam a matar milhares de pessoas e um tratamento eficaz e com sucesso tem sido um desafio. O mesmo se passa com algumas infeções virais, nomeadamente infeções provocadas pelo HIV. Para contornar os obstáculos enfrentados na terapia destas doenças têm sido usados análogos de nucleótidos e/ou nucleósidos como agentes terapêuticos. Estes têm o propósito de inibir a síntese de novo dos nucleótidos em determinadas etapas, estando envolvidos na replicação e síntese do RNA e DNA nas células em divisão. Atuam por inibição específica de enzimas no metabolismo dos nucleótidos/nucleósidos ou ainda por incorporação no DNA ou no RNA. This study will be developed into two main subjects; one related to the use of compounds which interfere with the metabolism of purine- and pyrimidine- nucleotides as antineoplastic agents; another related to their use as antiviral agents. The nucleotides’ synthesis involves the construction of nucleic acids and the introduction of the nucleotides’ derivatives into other biochemical pathways and it is responsible for numerous functions of cellular metabolism. There are pathologies involving key enzymes from the nucleotides’ metabolism, which led to the synthesis of new drugs. Cancer is a disease that continues killing thousands of people, an effective and successful treatment has been a challenge. The same happens with some viral infections, mainly infections caused by HIV. To overcome the obstacles faced in the therapy of these diseases it has been used nucleotide and/or nucleoside analogues as therapeutic agents. These agents have the purpose of inhibiting the de novo nucleotide synthesis in certain steps, by being involved in RNA and DNA replication and synthesis in dividing cells. They act by specific enzymes inhibition in nucleotide/nucleoside metabolism and by incorporation into DNA or RNA.
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Berthod, Thomas. "Synthèse d'oligonucléotides comportant des lésions radio- et photo-induites des bases pyrimidiques." Université Joseph Fourier (Grenoble ; 1971-2015), 1996. http://www.theses.fr/1996GRE10224.

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De nombreuses modifications des bases de l'adn peuvent etre generees par divers facteurs comme les agents oxydants ou cancerigenes, les rayonnements afin d'evaluer les consequences biologiques et physico-chimiques de ces dommages, il est necessaire de posseder des modeles plus complexes de ceux-ci qui peuvent etre obtenus par leur incorporation dans des oligonucleotides par voie chimique. Ce travail est consacre a la preparation de fragments d'adn contenant des derives de la 2'-desoxyuridine. Le premier volet de ce travail a consiste a preparer un synthon phosphoramidite de la 5-formyl-2'-desoxyuridine et a l'incorporer dans des oligonucleotides de synthese. La suite de ce travail concerne la mise en evidence et la caracterisation d'une nouvelle lesion, resultant de l'oxydation de la thymidine: la 5-carboxy-2'-desoxyuridine. Par ailleurs, la preparation d'oligonucleotides comportant cette lesion a ete realisee. La troisieme partie de ce travail correspond a l'incorporation d'un troisieme defaut dans des oligonucleotides: la 5,6-dihydro-2'-desoxyuridine (dhdu). Une etude plus complete sur les produits de degradation de cette lesion, susceptibles de se former en milieu alcalin, a ete ensuite menee avec le monomere et avec un trinucleotide, d(gdhdut). Dans une derniere partie, la recherche de conditions analytiques de separation de produits d'oxydation de la thymidine par electrophorese capillaire est presentee
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Eguae, Samuel Iyamu. "Pyrimidine nucleotide metabolism in Rhizobium meliloti: purification of aspartate transcarbamoylase from a pyrimidine auxotroph." Thesis, University of North Texas, 1990. https://digital.library.unt.edu/ark:/67531/metadc332674/.

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Rhizobium aspartate transcarbamoylase (ATCase; EC 2.1.3.2) was previously believed to be similar to the Pseudomonas ATCase which has been studied extensively. To facilitate the study of the Rhizobium ATCase a pyrimidine-requiring mutant of R. meliloti was isolated and used in the purification of the enzyme.
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Stewart, John E. B. (John Edward Bakos). "Characterization of Aspartate Transcarbamoylase in the Archaebacterium Methanococcus Jannaschii." Thesis, University of North Texas, 1996. https://digital.library.unt.edu/ark:/67531/metadc935724/.

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Asparate transcarbamoylase catalyzes the first committed step in the de novo synthesis of pyrmidine nucleotides UMP, UDP, UTP, and CTP. The archetype enzyme found in Escherichia coli (310 kDa) exhibits sigmodial substrate binding kinetics with positive control by ATP and negative control with CTP and UTP. The ATCase characterized in this study is from the extreme thermophilic Archaebacterium, Methanococcus jannaschii. The enzyme was very stable at elevated temperatures and possessed activity from 20 degrees Celsius to 90 degrees Celsius. M. Jannaschii ATCase retained 75% of its activity after incubation at 100 degrees Celsius for a period of 90 minutes. No sigmodial allosteric response to substrate for the enzyme was observed. Velocity substrate plots gave Michaelis-Menten (hyperbolic) kinetics. The Km for aspartate was 7 mM at 30 degrees Celsius and the KM for carbamoylphosphate was .125 mM. The enzyme from M. jannaschii had a broad pH response with an optimum above pH 9. Kinetic measurements were significantly affected by changes in pH and temperature. The enzyme catalyzed reaction had an energy of activation of 10,300 calories per mole. ATCase from M. jannaschii was partially purified. The enzyme was shown to have a molecular weight of 110,000 Da., with a subunit molecular weight of 37,000 Da. The enzyme was thus a trimer composed of three identical subunits. The enzyme did not possess any regulatory response and no evidence for a regulatory polypeptide was found, DNA from M. jannaschii did hybridize to probes corresponding to genes for both the catalytic and regulatory subunits from E. coli. Analysis of DNA sequences for the M. jannaschii ATCase genes showed that the gene for the catalytic subunits shares significant homology with the pyrB genes from E. coli, and maximum homology amongst known ATCase genes to pyrB from Bacillus. An unlinked gene homologous to E. coli pyrl encoding the regulatory subunit was identified, though its expression and true function remain uncharacterized.
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Le, Hir de Fallois Loic. "Synthèse et étude de nucléosides et nucléotides inhibiteurs de la ribonucléotide réductase." Université Joseph Fourier (Grenoble), 1995. http://www.theses.fr/1995GRE10158.

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La ribonucleotide reductase (rnr) est l'enzyme qui catalyse la reduction des ribonucleotides en desoxyribonucleotides. En raison de son role fondamental dans la synthese de l'adn, cette enzyme est une cible cle de la recherche de nouveaux agents antitumoraux. Dans le but d'inhiber cette enzyme nous avons synthetise des analogues de substrats. Nous avons synthetise et etudie les proprietes des premiers nucleosides thionitrites, les 2'-desoxy-2'-s-nitroso-uridine et -cytidine. Nous avons demontre que ces thionitrites liberent du monoxyde d'azote (no) qui est un inhibiteur de la ribonucleotide reductase. La synthese des thiols nucleosidiques a ete mise a profit pour preparer et obtenir de nouveaux derives thioethers qui pourraient presenter des proprietes alkylantes. La protection de la fonction thiol sous forme de disulfure mixte a ete etudiee et a permis de realiser la synthese de composes diphosphates. Les premieres syntheses du disulfure de propyle et de 5'-o-diphosphate-2'-desoxyuridin-2'-yle et de la 5'-o-diphosphate-2'-desoxy-2'-mercaptouridine ont ainsi ete realisees. La synthese du thiol diphosphate a permis de demontrer son tres fort effet inhibiteur de la rnr d'escherichia coli et d'etudier en detail son mode d'action. Nous avons montre que la 5'-diphosphate-2'-desoxy-2'-mercaptouridine est un inhibiteur suicide remarquable et que l'inactivation procede par la reduction du radical tyrosinyle de la rnr. La disparition du radical tyrosinyle s'accompagne de la formation d'une nouvelle espece radicalaire detectee en spectrometrie de rpe et il s'agirait d'un radical perthiyle situe sur une cysteine de l'enzyme. Ce resultat constitue la deuxieme detection directe d'un radical perthiyle situe sur une proteine
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9

So, Ngar-chung Nellie. "Pyrimidine nucleotide biosynthesis in adult angiostrongylus Cantonensis (Nematoda : Metastrongyloidea) /." [Hong Kong : University of Hong Kong], 1993. http://sunzi.lib.hku.hk/hkuto/record.jsp?B13637745.

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Collins, James P. "Prebiotic Synthesis of Pyrimidine Nucleosides." Thesis, Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/14095.

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The problem of forming a glycosidic bond between ribose and the free nucleoside bases to produce beta-nucleosides under plausible prebiotic conditions is commonly referred to in origin of life research as The Nucleoside Problem. The lack of a general solution to this problem currently represents one of the largest stumbling blocks to the RNA world hypothesis and many other theories regarding the origin of life. Over thirty years ago the purine nucleosides were successfully synthesized by drying the fully-formed bases and ribose together in the presence of divalent metal ion salts. However, glycosidic bond formation by the pyrimidine bases has never been achieved under similar reaction conditions. This thesis describes the first plausible prebiotic synthesis of a pyrimidine nucleoside, demonstrated with the pyrimidine base analogue 2-pyrimidinone. Information provided by nucleoside-formation reaction involving 2-pyrimidinone and related pyrimidine bases should provide valuable insights into the possible mechanism by which glycosidic bond formation was accomplished on the prebiotic Earth.
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Books on the topic "Synthesis of pyrimidine nucleotides"

1

Pharmacology of purine and pyrimidine receptors. San Diego, CA: Elsevier, 2011.

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Teshiba, Sadao. Production of nucleotides and nucleosides by fermentation. New York: Gordon and Breach Science Publishers, 1989.

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Reiner, Tilman. [Beta]-eliminierbare Schutzgruppen als allgemeines Prinzip in der Oligonucleotidchemie: Ein Beitrag zur automatisierten Synthese von Oligonucleotiden. Konstanz: Hartung-Gorre, 1988.

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Schwarz, Michael Walter. Synthese von Oligonukleotiden und Nukleotiden mit terminaler Phosphotriester- und Thiophosphotriesterfunktion mit Hilfe neuer Phosphor (III) Verbindungen nach der Phosphitamidmethode. Konstanz: Hartung-Gorre, 1986.

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Pfleiderer, Mathias. Synthese und Eigenschaften 6-substituierter Pyrido[2,3-d]pyrimidine. Konstanz: Hartung-Gorre, 1986.

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M, Bezborodov A., ed. Mikrobiologicheskiĭ sintez nukleozidfosfatov. Moskva: "Nauka", 1990.

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Ruf, Klaus. Synthese biologisch interessanter Nukleoside und Oligonukleotide. Konstanz: Hartung-Gorre, 1987.

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Forman, Gary. The synthesis of potential anti-hepatitis B virus nucleotides. Birmingham: University of Birmingham, 1994.

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Tusa, Girolamo. Synthesis and biological activity of conformationally constrained nucleosides and nucleotides. Ottawa: National Library of Canada, 1998.

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Steppan, Heinz. Mehrfache und selektive elektrochemische Schutzgruppenabspaltung in der Oligonucleotidsynthese. Konstanz: Hartung-Gorre, 1985.

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Book chapters on the topic "Synthesis of pyrimidine nucleotides"

1

Ueda, Tohru. "Synthesis and Reaction of Pyrimidine Nucleosides." In Chemistry of Nucleosides and Nucleotides, 1–112. Boston, MA: Springer US, 1988. http://dx.doi.org/10.1007/978-1-4613-0995-6_1.

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Switzer, Robert L., and Cheryl L. Quinn. "De Novo Pyrimidine Nucleotide Synthesis." In Bacillus subtilis and Other Gram-Positive Bacteria, 343–58. Washington, DC, USA: ASM Press, 2014. http://dx.doi.org/10.1128/9781555818388.ch25.

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Lin, Tai-Shun, and Mao-Chin Liu. "Synthesis and Anticancer and Antiviral Activity of Certain Pyrimidine Nucleoside Analogues." In Nucleosides and Nucleotides as Antitumor and Antiviral Agents, 177–201. Boston, MA: Springer US, 1993. http://dx.doi.org/10.1007/978-1-4615-2824-1_10.

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Rowe, Peter B., Sandra E. McEwen, and Annette Kalaizis. "Purine Nucleotide Synthesis in Cultured Rat Embryos Undergoing Organogenesis." In Purine and Pyrimidine Metabolism in Man V, 541–46. New York, NY: Springer US, 1986. http://dx.doi.org/10.1007/978-1-4684-1248-2_84.

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Yokoyama, Hiroomi, Keiichi Okamoto, Hiroyuki Nogawa, Shinsaku Naitou, and Mitsuo Itakura. "A Nucleoside Mixture and its Sparing Effect on de novo Purine Nucleotide Synthesis." In Purine and Pyrimidine Metabolism in Man VIII, 541–44. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4615-2584-4_114.

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Kumar, Vipan, and Mohinder P. Mahajan. "Pyrimidine and Imidazole." In Heterocycles in Natural Product Synthesis, 507–33. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2011. http://dx.doi.org/10.1002/9783527634880.ch14.

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Sulkowska, Anna. "Association of pyrimidine nucleotides with unfolded albumin." In Spectroscopy of Biological Molecules: New Directions, 267–68. Dordrecht: Springer Netherlands, 1999. http://dx.doi.org/10.1007/978-94-011-4479-7_117.

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Connolly, G. P. "Uridine and Pyrimidine Nucleotides in Cell Function." In Purinergic and Pyrimidinergic Signalling I, 403–21. Berlin, Heidelberg: Springer Berlin Heidelberg, 2001. http://dx.doi.org/10.1007/978-3-662-09604-8_14.

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Rudolph, Frederick B., William C. Fanslow, Anil D. Kulkarni, Sulabha S. Kulkarni, and Charles T. Van Buren. "Effect of Dietary Nucleotides on Lymphocyte Maturation." In Purine and Pyrimidine Metabolism in Man V, 497–501. Boston, MA: Springer US, 1986. http://dx.doi.org/10.1007/978-1-4684-5104-7_83.

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Peters, Godefridus J. "Therapy Related Disturbances in Nucleotides in Cancer Cells." In Purine and Pyrimidine Metabolism in Man VIII, 95–107. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4615-2584-4_24.

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Conference papers on the topic "Synthesis of pyrimidine nucleotides"

1

Meier, Chris, Edwuin Hander Rios Morales, Cristina Arbelo Román, and Jan Balzarini. "Stereoselective synthesis of 3-methyl-cycloSal-nucleotides." In XVth Symposium on Chemistry of Nucleic Acid Components. Prague: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 2011. http://dx.doi.org/10.1135/css201112033.

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Gulyaeva, Irina V., Ekaterina V. Efimtseva, Andrei A. Rodionov, Boris S. Ermolinsky, and Sergey N. Mikhailov. "Direct synthesis of 5'-nucleotides using glycosylation reaction." In XIIth Symposium on Chemistry of Nucleic Acid Components. Prague: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 2002. http://dx.doi.org/10.1135/css200205312.

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Kowalska, Joanna, Marek R. Baranowski, Anna Nowicka, Renata Kasprzyk, Joanna Zuberek, Jacek Wojcik, and Jacek Jemielity. "Synthesis and properties of nucleotides containing a fluorophosphate moiety." In XVIth Symposium on Chemistry of Nucleic Acid Components. Prague: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 2014. http://dx.doi.org/10.1135/css201414159.

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Rejman, Dominik, Petr Kočalka, Radek Pohl, and Ivan Rosenberg. "Synthesis of 4'-N pyrrolidine nucleosides, nucleotides, and oligonucleotides." In XIIIth Symposium on Chemistry of Nucleic Acid Components. Prague: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 2005. http://dx.doi.org/10.1135/css200507159.

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Shutalev, Anatoly, and Anastasia Fesenko. "Synthesis of 5-(diethoxyphosphoryl)-substituted Hydrogenated Pyrimidine-2-thiones." In The 11th International Electronic Conference on Synthetic Organic Chemistry. Basel, Switzerland: MDPI, 2007. http://dx.doi.org/10.3390/ecsoc-11-01328.

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Xavier, Augusto L., Daniel S. Alexandrino, Emerson P. S. Falcão, Rajendra M. Srivastava, and Janaina V. dos Anjos. "A green, microwave-mediated, multicomponent synthesis of pyrimidine and pyrimidinone derivatives." In 14th Brazilian Meeting on Organic Synthesis. São Paulo: Editora Edgard Blücher, 2013. http://dx.doi.org/10.5151/chempro-14bmos-r0024-1.

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Scapin, Elisandra, Lilian Buriol, Taiana Scalco München, Clarissa Piccinin Frizzo, and Marcos A. P. Martins. "Synthesis of 1,2,4-Triazolo[1,5-a]pyrimidine Supported under Ultrasound Irradiation." In 15th Brazilian Meeting on Organic Synthesis. São Paulo: Editora Edgard Blücher, 2013. http://dx.doi.org/10.5151/chempro-15bmos-bmos2013_20131012143813.

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Vrabel, Milan, and Michal Hocek. "Synthesis of modified nucleosides, nucleotides and oligonucleotides bearing metal complexes." In XIVth Symposium on Chemistry of Nucleic Acid Components. Prague: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 2008. http://dx.doi.org/10.1135/css200810182.

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Kalachova, Lubica, and Michal Hocek. "Synthesis of nucleotides bearing oligopyridine ligands and their incorporation into DNA." In XVth Symposium on Chemistry of Nucleic Acid Components. Prague: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 2011. http://dx.doi.org/10.1135/css201112357.

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Ferreira, Marcelle de Souza, and José Daniel Figueroa Villar. "Synthesis of news furo[2,3-d] pyrimidine derivatives as potential inhibitors of DHFR." In 15th Brazilian Meeting on Organic Synthesis. São Paulo: Editora Edgard Blücher, 2013. http://dx.doi.org/10.5151/chempro-15bmos-bmos2013_2013913121221.

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