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Artykuły w czasopismach na temat „Thymidine monophosphate”

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Data publikacji: 6 września 2023

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1

Miyasaki, Taiko, i Katsuhiko Harada. "Effects of specific purine and pyrimidine compounds on the ingestion of test diets by the abalone Haliotis discus and the oriental weatherfish Misgurnus anguillicaudatus". Marine and Freshwater Research 54, nr 3 (2003): 235. http://dx.doi.org/10.1071/mf02066.

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To improve the feed ingestion of cultured fish and shellfish, 26 purine and pyrimidine compounds were examined as dietary supplements at a concentration of 1.0 mmol kg–1 (or L–1) of diet. For the black abalone Haliotis discus, feeding was significantly (P < 0.05) increased by thymidine, adenosine-5�-monophosphate, adenosine- 5�-diphosphate (ADP), adenosine-5�-triphosphate, guanosine-5�-monophosphate (GMP), inosine-5- monophosphate (IMP) and 2�-deoxycytidine-5�-monophosphate. For the oriental weatherfish Misgurnus anguillicaudatus, feeding was significantly (P < 0.05) increased by thymidine, ADP, IMP and thymidine-5�-monophosphate (TMP). At one-tenth of the initial concentration, ADP, GMP and IMP were effective for the abalone and thymidine and TMP were effective for the weatherfish. None of the compounds inhibited feeding of either species.

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2

Gogolin, Lars, Ralf Seidel, Martin Engelhard, Roger S. Goody i Christian F. W. Becker. "Semisynthesis of human thymidine monophosphate kinase". Biopolymers 94, nr 4 (3.06.2010): 433–40. http://dx.doi.org/10.1002/bip.21398.

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3

Wu, R. R., L. A. Hamlow, C. C. He, Y. w. Nei, G. Berden, J. Oomens i M. T. Rodgers. "The intrinsic basicity of the phosphate backbone exceeds that of uracil and thymine residues: protonation of the phosphate moiety is preferred over the nucleobase for pdThd and pUrd". Physical Chemistry Chemical Physics 19, nr 45 (2017): 30351–61. http://dx.doi.org/10.1039/c7cp05521h.

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4

Thompson, L. F. "Ecto-5'-nucleotidase can provide the total purine requirements of mitogen-stimulated human T cells and rapidly dividing human B lymphoblastoid cells." Journal of Immunology 134, nr 6 (1.06.1985): 3794–97. http://dx.doi.org/10.4049/jimmunol.134.6.3794.

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Abstract The ability of mitogen-stimulated human T cells or rapidly dividing human B lymphoblastoid cells to drive their total purine requirements from inosine 5'-monophosphate, inosine, or hypoxanthine was compared. Inosine 5'-monophosphate first must be converted to inosine by the action of the enzyme ecto-5'-nucleotidase before it can be transported into the cell; inosine and hypoxanthine, however, can be transported directly. Mitogen-stimulated human peripheral blood T cells were treated with aminopterin to inhibit purine synthesis de novo and to make the cells dependent on an exogenous purine source. Thymidine was added as a source of pyrimidines. Under these conditions, 30 microM inosine 5'-monophosphate, inosine, and hypoxanthine showed comparable abilities to support [3H]thymidine incorporation into DNA or [3H]leucine incorporation into protein at rates equal to that of untreated control cultures. Similar results were found when azaserine was used to inhibit purine synthesis de novo, and thus DNA synthesis. In parallel experiments with the rapidly dividing human B lymphoblastoid cell line WI-L2, treatment with aminopterin (plus thymidine) inhibited the growth rate by greater than 95%. The normal growth rate was restored by the addition of 30 microM inosine 5'-monophosphate, inosine, or hypoxanthine to the medium. However, in similar experiments with cell line 1254, a derivative of WI-L2 which lacks detectable ecto-5'-nucleotidase activity, inosine and hypoxanthine (plus thymidine), but not inosine 5'-monophosphate (and thymidine) were able to restore the growth inhibition due to aminopterin. These results show that the catalytic activity of ecto-5'-nucleotidase is sufficient to meet the total purine requirements of mitogen-stimulated human T cells or rapidly dividing human B lymphoblastoid cells, and suggest that this enzyme may be important for purine salvage when rates of purine synthesis de novo are limited and/or an extracellular source of purine nucleotides is available.

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5

Gul, Sana, Ruqaiya Khalil, Zaheer Ul-Haq i Mohammad S. Mubarak. "Computational Overview of Mycobacterial Thymidine Monophosphate Kinase". Current Pharmaceutical Design 26, nr 15 (18.05.2020): 1676–81. http://dx.doi.org/10.2174/1381612826666200403114152.

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: Tuberculosis (TB) ranks among the diseases with the highest morbidity rate with significantly high prevalence in developing countries. Globally, tuberculosis poses the most substantial burden of mortality. Further, a partially treated tuberculosis patient is worse than untreated; they may lead to standing out as a critical obstacle to global tuberculosis control. The emergence of multi-drug resistant (MDR) and extremely drug-resistant (XDR) strains, and co-infection of HIV further worsen the situation. The present review article discusses validated targets of the bacterial enzyme thymidine monophosphate kinase (TMPK). TMPKMTB enzyme belongs to the nucleoside monophosphate kinases (NMPKs) family. It is involved in phosphorylation of TMP to TDP, and TDP is phosphorylated to TTP. This review highlights structure elucidation of TMP enzymes and their inhibitors study on TMP scaffold, and it also discusses different techniques; including molecular docking, virtual screening, 3DPharmacophore, QSAR for finding anti-tubercular agents.

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6

Gustavsson, Thomas, Alexei Sharonov i Dimitra Markovitsi. "Thymine, thymidine and thymidine 5′-monophosphate studied by femtosecond fluorescence upconversion spectroscopy". Chemical Physics Letters 351, nr 3-4 (styczeń 2002): 195–200. http://dx.doi.org/10.1016/s0009-2614(01)01375-6.

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Schlosser, Julika, Julian F. M. Hebborn, Daria V. Berdnikova i Heiko Ihmels. "Selective Fluorimetric Detection of Pyrimidine Nucleotides in Neutral Aqueous Solution with a Styrylpyridine-Based Cyclophane". Chemistry 5, nr 2 (11.05.2023): 1220–32. http://dx.doi.org/10.3390/chemistry5020082.

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A styrylpyridine-containing cyclophane with diethylenetriamine linkers is presented as a host system whose association with representative nucleotides was examined with photometric and fluorimetric titrations. The spectrometric titrations revealed the formation of 1:1 complexes with log Kb values in the range of 2.3–3.2 for pyrimidine nucleotides TMP (thymidine monophosphate), TTP (thymidine triphosphate) and CMP (cytidine monophosphate) and 3.8–5.0 for purine nucleotides AMP (adenosine monophosphate), ATP (adenosine triphosphate), and dGMP (deoxyguanosine monophosphate). Notably, in a neutral buffer solution, the fluorimetric response to the complex formation depends on the type of nucleotide. Hence, quenching of the already weak fluorescence was observed with the purine bases, whereas the association of the cyclophane with pyrimidine bases TMP, TTP, and CMP resulted in a significant fluorescence light-up effect. Thus, it was demonstrated that the styrylpyridine unit is a useful and complementary fluorophore for the development of selective nucleotide-targeting fluorescent probes based on alkylamine-linked cyclophanes.

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8

Tomasz, Jeno, Barbara Ramsay Shaw, Ken Porter, Bernard F. Spielvogel i Anup Sood. "5′-P-Borane-Substituted Thymidine Monophosphate and Triphosphate". Angewandte Chemie International Edition in English 31, nr 10 (październik 1992): 1373–75. http://dx.doi.org/10.1002/anie.199213731.

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9

Van Poecke, Sara, Hélène Munier-Lehmann, Olivier Helynck, Matheus Froeyen i Serge Van Calenbergh. "Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase". Bioorganic & Medicinal Chemistry 19, nr 24 (grudzień 2011): 7603–11. http://dx.doi.org/10.1016/j.bmc.2011.10.021.

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10

Keita, M., A. Kumar, B. Dali, E. Megnassan, M. I. Siddiqi, V. Frecer i S. Miertus. "Quantitative structure–activity relationships and design of thymine-like inhibitors of thymidine monophosphate kinase of Mycobacterium tuberculosis with favourable pharmacokinetic profiles". RSC Adv. 4, nr 99 (2014): 55853–66. http://dx.doi.org/10.1039/c4ra06917j.

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11

Mukhina, T. M. "The effect of chlorination of nucleotide bases on the conformational properties of thymidine monophosphate". Ukrainian Biochemical Journal 87, nr 2 (27.04.2015): 141–55. http://dx.doi.org/10.15407/ubj87.02.141.

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12

Vanheusden, Veerle, Philippe Van Rompaey, Hélène Munier-Lehmann, Sylvie Pochet, Piet Herdewijn i Serge Van Calenbergh. "Thymidine and thymidine-5′-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase". Bioorganic & Medicinal Chemistry Letters 13, nr 18 (wrzesień 2003): 3045–48. http://dx.doi.org/10.1016/s0960-894x(03)00643-7.

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13

Hellendahl, Katja F., Sarah Kamel, Albane Wetterwald, Peter Neubauer i Anke Wagner. "Human Deoxycytidine Kinase Is a Valuable Biocatalyst for the Synthesis of Nucleotide Analogues". Catalysts 9, nr 12 (27.11.2019): 997. http://dx.doi.org/10.3390/catal9120997.

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Natural ribonucleoside-5’-monophosphates are building blocks for nucleic acids which are used for a number of purposes, including food additives. Their analogues, additionally, are used in pharmaceutical applications. Fludarabine-5´-monophosphate, for example, is effective in treating hematological malignancies. To date, ribonucleoside-5’-monophosphates are mainly produced by chemical synthesis, but the inherent drawbacks of this approach have led to the development of enzymatic synthesis routes. In this study, we evaluated the potential of human deoxycytidine kinase (HsdCK) as suitable biocatalyst for the synthesis of natural and modified ribonucleoside-5’-monophosphates from their corresponding nucleosides. Human dCK was heterologously expressed in E. coli and immobilized onto Nickel-nitrilotriacetic acid (Ni-NTA) superflow. A screening of the substrate spectrum of soluble and immobilized biocatalyst revealed that HsdCK accepts a wide range of natural and modified nucleosides, except for thymidine and uridine derivatives. Upon optimization of the reaction conditions, HsdCK was used for the synthesis of fludarabine-5´-monophosphate using increasing substrate concentrations. While the soluble biocatalyst revealed highest product formation with the lowest substrate concentration of 0.3 mM, the product yield increased with increasing substrate concentrations in the presence of the immobilized HsdCK. Hence, the application of immobilized HsdCK is advantageous upon using high substrate concentration which is relevant in industrial applications.

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14

Susan-Resiga, Delia, Alice T. Bentley, Matthew D. Lynx, Darcy D. LaClair i Edward E. McKee. "Zidovudine Inhibits Thymidine Phosphorylation in the Isolated Perfused Rat Heart". Antimicrobial Agents and Chemotherapy 51, nr 4 (12.01.2007): 1142–49. http://dx.doi.org/10.1128/aac.01227-06.

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ABSTRACT Zidovudine (AZT; 3′-azido-3′-deoxythymidine), a thymidine analog, has been a staple of highly active antiretroviral therapy. It is phosphorylated in the host to the triphosphate and functions by inhibiting the viral reverse transcriptase. However, long-term use of AZT is linked to various tissue toxicities, including cardiomyopathy. These toxicities are associated with mitochondrial DNA depletion, which is hypothesized to be caused by AZT triphosphate inhibition of mitochondrial DNA polymerase γ. In previous work with isolated heart mitochondria, we demonstrated that AZT phosphorylation beyond the monophosphate was not detected and that AZT itself was a potent inhibitor of thymidine phosphorylation. This suggests an alternative hypothesis in which depletion of the TTP pool may limit mitochondrial DNA replication. The present work extends these studies to the whole cell by investigating the metabolism of thymidine and AZT in the intact isolated perfused rat heart. [3H]thymidine is converted to [3H]TTP in a time- and concentration-dependent manner. The level of [3H]TMP is low, suggesting that the reaction catalyzed by thymidine kinase is the rate-limiting step in phosphorylation. [3H]AZT is converted in a time- and concentration-dependent manner to AZT monophosphate, the only phosphorylated product detected after 3 h of perfusion. Both compounds display negative cooperativity, similar to the observations with cloned and purified mitochondrial thymidine kinase 2. The presence of AZT in the perfusate inhibits the phosphorylation of [3H]thymidine with a 50% inhibitory concentration of 24 ± 4 μM. These data support the hypothesis that AZT-induced mitochondrial cardiotoxicity may be caused by a limiting pool of TTP that lowers mitochondrial DNA replication.

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15

Chen, Bi-Xing, Karen Hubbard, Hiroshi Ide, Susan S. Wallace i Bernard F. Erlanger. "Characterization of a Monoclonal Antibody to Thymidine Glycol Monophosphate". Radiation Research 124, nr 2 (listopad 1990): 131. http://dx.doi.org/10.2307/3577856.

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16

Garone, Caterina, Beatriz Garcia‐Diaz, Valentina Emmanuele, Luis C. Lopez, Saba Tadesse, Hasan O. Akman, Kurenai Tanji, Catarina M. Quinzii i Michio Hirano. "Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency". EMBO Molecular Medicine 6, nr 8 (26.06.2014): 1016–27. http://dx.doi.org/10.15252/emmm.201404092.

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Gabryel-Skrodzka, Malwina, Martyna Nowak, Anna Teubert i Renata Jastrzab. "Coordination Chemistry of Phosphate Groups in Systems Including Copper(II) Ions, Phosphoethanolamine and Pyrimidine Nucleotides". International Journal of Molecular Sciences 23, nr 22 (8.11.2022): 13718. http://dx.doi.org/10.3390/ijms232213718.

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The activity of phosphate groups of phosphoethanolamine and pyrimidine nucleotides (thymidine 5-monophosphate, cytidine 5-monophosphate and uridine 5’monophosphate) in the process of complexation metal ions in aqueous solution was studied. Using the potentiometric method with computer calculation of the data and spectroscopic methods such as UV-Vis, EPR, 13C and 31P NMR as well as FT-IR, the overall stability constants of the complexes as well as coordination modes were obtained. At lower pH, copper(II) ions are complexed only by phosphate groups, whereas the endocyclic nitrogen atom of nucleotides has been identified as a negative center interacting with the -NH3+ groups of phosphoethanolamine.

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18

Busam, Robert D. "Structure ofEscherichia coliexonuclease I in complex with thymidine 5′-monophosphate". Acta Crystallographica Section D Biological Crystallography 64, nr 2 (16.01.2008): 206–10. http://dx.doi.org/10.1107/s090744490706012x.

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19

Lee, Hyeon Cheol, Jung Mi Ahn, Sang Nam Lee i Jung Hoe Kim. "Overproduction of thymidine by recombinant Brevibacterium helvolum amplified with thymidine monophosphate phosphohydrolase gene from bacteriophage PBS2". Biotechnology Letters 26, nr 4 (luty 2004): 265–68. http://dx.doi.org/10.1023/b:bile.0000015423.83278.e2.

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Frecer, Vladimir, Pierfausto Seneci i Stanislav Miertus. "Computer-assisted combinatorial design of bicyclic thymidine analogs as inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase". Journal of Computer-Aided Molecular Design 25, nr 1 (17.11.2010): 31–49. http://dx.doi.org/10.1007/s10822-010-9399-4.

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Rhaman, Md Mhahabubur, Douglas R. Powell i Md Alamgir Hossain. "Supramolecular Assembly of Uridine Monophosphate (UMP) and Thymidine Monophosphate (TMP) with a Dinuclear Copper(II) Receptor". ACS Omega 2, nr 11 (10.11.2017): 7803–11. http://dx.doi.org/10.1021/acsomega.7b01293.

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Owono Owono, Luc Calvin, Melalie Keita, Eugene Megnassan, Vladimir Frecer i Stanislav Miertus. "Design of Thymidine Analogues Targeting Thymidilate Kinase ofMycobacterium tuberculosis". Tuberculosis Research and Treatment 2013 (2013): 1–13. http://dx.doi.org/10.1155/2013/670836.

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We design here new nanomolar antituberculotics, inhibitors ofMycobacterium tuberculosisthymidine monophosphate kinase (TMPKmt), by means of structure-based molecular design. 3D models of TMPKmt-inhibitor complexes have been prepared from the crystal structure of TMPKmtcocrystallized with the natural substrate deoxythymidine monophosphate (dTMP) (1GSI) for a training set of 15 thymidine analogues (TMDs) with known activity to prepare a QSAR model of interaction establishing a correlation between the free energy of complexation and the biological activity. Subsequent validation of the predictability of the model has been performed with a 3D QSAR pharmacophore generation. The structural information derived from the model served to design new subnanomolar thymidine analogues. From molecular modeling investigations, the agreement between free energy of complexation (ΔΔGcom) andKivalues explains 94% of the TMPKmtinhibition (pKi=-0.2924ΔΔGcom+3.234;R2=0.94) by variation of the computedΔΔGcomand 92% for the pharmacophore (PH4) model (pKi=1.0206×pKipred-0.0832, R2=0.92). The analysis of contributions from active site residues suggested substitution at the 5-position of pyrimidine ring and various groups at the 5′-position of the ribose. The best inhibitor reached a predictedKiof 0.155 nM. The computational approach through the combined use of molecular modeling and PH4 pharmacophore is helpful in targeted drug design, providing valuable information for the synthesis and prediction of activity of novel antituberculotic agents.

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23

Kira, Toshihiko, Susan P. Grill, Ginger E. Dutschman, Ju-Sheng Lin, Fucheng Qu, Yongseok Choi, Chung K. Chu i Yung-Chi Cheng. "Anti-Epstein-Barr Virus (EBV) Activity of β-l-5-Iododioxolane Uracil Is Dependent on EBV Thymidine Kinase". Antimicrobial Agents and Chemotherapy 44, nr 12 (1.12.2000): 3278–84. http://dx.doi.org/10.1128/aac.44.12.3278-3284.2000.

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ABSTRACT β-l-5-Iododioxolane uracil was shown to have potent anti-Epstein-Barr virus (EBV) activity (50% effective concentration = 0.03 μM) with low cytotoxicity (50% cytotoxic concentration = 1,000 μM). It exerts its antiviral activity by suppressing replicative EBV DNA and viral protein synthesis. This compound is phosphorylated in cells where the EBV is replicating but not in cells where the EBV is latent. EBV-specific thymidine kinase could phosphorylate β-l-5-iododioxolane uracil to the monophosphate metabolite. The Km of β-l-5-iododioxolane uracil with EBV thymidine kinase was estimated to be 5.5 μM, which is similar to that obtained with thymidine but about fivefold higher than that obtained with 2′ fluoro-5-methyl-β-l-arabinofuranosyl uracil, the firstl-nucleoside analogue discovered to have anti-EBV activity. The relative V max is seven times higher than that of thymidine. The anti-EBV activity of β-l-5-iododioxolane uracil and its intracellular phosphorylation could be inhibited by 5′-ethynylthymidine, a potent EBV thymidine kinase inhibitor. The present study suggests that β-l-5-iododioxolane uracil exerts its action after phosphorylation; therefore, EBV thymidine kinase is critical for the antiviral action of this drug.

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Erickson, Blake A., Zachary N. Heim, Elisa Pieri, Erica Liu, Todd J. Martinez i Daniel M. Neumark. "Relaxation Dynamics of Hydrated Thymine, Thymidine, and Thymidine Monophosphate Probed by Liquid Jet Time-Resolved Photoelectron Spectroscopy". Journal of Physical Chemistry A 123, nr 50 (22.11.2019): 10676–84. http://dx.doi.org/10.1021/acs.jpca.9b08258.

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Gasse, C., V. Huteau, D. Douguet, H. Munier-Lehmann i S. Pochet. "A New Family of Inhibitors of Mycobacterium Tuberculosis Thymidine Monophosphate Kinase". Nucleosides, Nucleotides & Nucleic Acids 26, nr 8-9 (26.11.2007): 1057–61. http://dx.doi.org/10.1080/15257770701513349.

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Ahmad, Rizwan, Khurshid Alam i Rashid Ali. "Antigen binding characteristics of antibodies against hydroxyl radical modified thymidine monophosphate". Immunology Letters 71, nr 2 (luty 2000): 111–15. http://dx.doi.org/10.1016/s0165-2478(99)00177-7.

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Grachev, S. A., E. V. Kropachev i G. I. Litvyakova. "Addition of cysteamine to thymine and thymidine monophosphate, initiated by ?-irradiation". Bulletin of the Academy of Sciences of the USSR Division of Chemical Science 34, nr 10 (październik 1985): 2178–84. http://dx.doi.org/10.1007/bf00963257.

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Mondal, Dibyendu, Eric M. Koehn, Jiajun Yao, David F. Wiemer i Amnon Kohen. "Chemo-enzymatic synthesis of the exocyclic olefin isomer of thymidine monophosphate". Bioorganic & Medicinal Chemistry 26, nr 9 (maj 2018): 2365–71. http://dx.doi.org/10.1016/j.bmc.2018.03.032.

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Avvakumova, Svetlana, Giorgio Scari i Francesca Porta. "Au–thymine, thymidine and thymidine 5′-monophosphate nanoparticles: chemical characterisation and cellular uptake studies into U87 cancer cells". RSC Advances 2, nr 9 (2012): 3658. http://dx.doi.org/10.1039/c2ra20386c.

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Van Rompaey, Philippe, Koen Nauwelaerts, Veerle Vanheusden, Jef Rozenski, Hélène Munier-Lehmann, Piet Herdewijn i Serge Van Calenbergh. "Mycobacterium tuberculosis Thymidine Monophosphate Kinase Inhibitors: Biological Evaluation and Conformational Analysis of 2′- and 3′-Modified Thymidine Analogues". European Journal of Organic Chemistry 2003, nr 15 (sierpień 2003): 2911–18. http://dx.doi.org/10.1002/ejoc.200300177.

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Lomozik, Lechoslaw, i Renata Jastrzab. "Noncovalent Interaction of Uridine 5′-Monophosphate with Adenosine, Cytidine, and Thymidine, as well as Adenosine 5′-Monophosphate and Cytidine 5′-Monophosphate in Aqueous Solution". Journal of Solution Chemistry 35, nr 2 (luty 2006): 161–77. http://dx.doi.org/10.1007/s10953-006-9376-7.

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Navé, Jean-François, Bernhard Neises i Anne Eschbach. "Study of Analogues of Thymidine-5′-Monophosphate and Thymidine as Substrates or Inhibitors of Chick Embryo Liver Thymidylate Kinase". Nucleosides and Nucleotides 15, nr 9 (wrzesień 1996): 1469–79. http://dx.doi.org/10.1080/07328319608002448.

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Van Daele, Ineke, Hélène Munier-Lehmann, Matheus Froeyen, Jan Balzarini i Serge Van Calenbergh. "Rational Design of 5‘-Thiourea-Substituted α-Thymidine Analogues as Thymidine Monophosphate Kinase Inhibitors Capable of Inhibiting Mycobacterial Growth". Journal of Medicinal Chemistry 50, nr 22 (listopad 2007): 5281–92. http://dx.doi.org/10.1021/jm0706158.

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NAVE, J. F., B. NEISES i A. ESCHBACH. "ChemInform Abstract: Analogues of Thymidine-5′-monophosphate and Thymidine as Substrates or Inhibitors of Chick Embryo Liver Thymidylate Kinase." ChemInform 28, nr 2 (4.08.2010): no. http://dx.doi.org/10.1002/chin.199702189.

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Brickute, D., A. Beckley, L. Allott, M. Braga, C. Barnes, K. J. Thorley i E. O. Aboagye. "Synthesis and evaluation of 3′-[18F]fluorothymidine-5′-squaryl as a bioisostere of 3′-[18F]fluorothymidine-5′-monophosphate". RSC Advances 11, nr 20 (2021): 12423–33. http://dx.doi.org/10.1039/d1ra00205h.

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Zhou, Ping, Qiong Xiao, Zhao-Ting Su, Lin Zhu, Fang-Xia Jin i Xuan-Yi Du. "Effect of parathyroid hormone-related protein on intracellular calcium ion and cyclic adenosine monophosphate concentrations in cardiac fibroblasts". Journal of International Medical Research 48, nr 9 (wrzesień 2020): 030006052093124. http://dx.doi.org/10.1177/0300060520931245.

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Objective This study aimed to determine the effect of parathyroid hormone-related protein (PTHrP) on proliferation of cardiac fibroblasts (CFs) in primary cultures of neonatal Wistar rats. Methods Different PTHrP concentrations were added to CFs of neonatal Wistar rats and the cells were grouped according to the concentrations added. A verapamil (VPL) group and a calcitriol (CAL) group were also established. Changes in cell proliferation and in cyclic adenosine monophosphate and calcium ion levels were identified and recorded. Results We found that as the concentration of PTHrP increased, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT, a tetrazolium salt) colorimetric absorbance values (A values) decreased. These values in the PTHrP groups were significantly lower than those in the control group. MTT colorimetric A values and 3H-thymidine deoxyribose intake were lower in the VPL group, low-dose CAL group, and the PTHrP 10−7 mol/L group compared with the control group. However, MTT colorimetric A values and 3H-thymidine deoxyribose intake were higher in the high-dose CAL group than in the PTHrP 10−7 mol/L group. As PTHrP concentrations increased, intracellular cyclic adenosine monophosphate concentrations also increased. Conclusion PTHrp, VPL, and low-dose CAL inhibit proliferation of CFs, while high-dose CAL promotes proliferation of CFs.

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Maruno, K., A. Absood i S. I. Said. "VIP inhibits basal and histamine-stimulated proliferation of human airway smooth muscle cells". American Journal of Physiology-Lung Cellular and Molecular Physiology 268, nr 6 (1.06.1995): L1047—L1051. http://dx.doi.org/10.1152/ajplung.1995.268.6.l1047.

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Airway smooth muscle (ASM) cell proliferation contributes to increased airway resistance in bronchial asthma. We have examined the modulation of ASM proliferation by vasoactive intestinal peptide (VIP), a cotransmitter of airway relaxation. Human ASM cells were grown in culture as a monolayer. VIP (1.0 nM-1.0 microM) inhibited proliferation in a dose-dependent manner by up to 82% on day 2, but the related peptide glucagon had no effect. Histamine (100 nM-100 microM) increased cell counts by 66%, but in the presence of VIP, cell counts and [3H]thymidine incorporation were reduced by up to 55%. Adenosine 3',5'-cyclic monophosphate (cAMP)-promoting agents, including 3-isobutyl-1-methylxanthine, forskolin, and 8-bromo-adenosine 3',5'-cyclic monophosphate, alone and especially combined with VIP, reduced cell counts and [3H]thymidine incorporation, in correlation with cAMP levels. KT-5720 (1.0 nM-1.0 microM), a selective inhibitor of cAMP-dependent protein kinase A (PKA), abolished the inhibitory effect of VIP. The results show that VIP selectively and potently inhibits human ASM cell growth and multiplication, and nullifies the mitogenic effect of histamine, by a PKA-mediated mechanism. A deficiency of VIP may lead to ASM hyperplasia due to unopposed stimulation by endogenous mitogens.

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Riegel, J. A., S. H. P. Maddrell, R. W. Farndale i F. M. Caldwell. "Stimulation of fluid secretion of malpighian tubules of drosophila melanogaster meig. by cyclic nucleotides of inosine, cytidine, thymidine and uridine". Journal of Experimental Biology 201, nr 24 (15.12.1998): 3411–18. http://dx.doi.org/10.1242/jeb.201.24.3411.

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External application of the 3',5'-cyclic monophosphates of inosine,cytidine, uridine and thymidine stimulated the fluid secretion rate (FSR)of Malpighian tubules isolated from Drosophila melanogaster. The evidence suggested that the cyclic nucleotides acted intracellularly in some capacity. Receptors of the 'purinergic' type appeared not to be major contributors to fluid secretion; of three purinergic agonists tried,adenosine, adenosine 5'-monophosphate (AMP) and adenosine 5'-triphosphate(ATP), only adenosine had an effect, but this was not observed consistently. None of the purinergic agonists interfered with the stimulation of the FSR by adenosine 3',5'-cyclic monophosphate (cAMP). The maximum stimulation of the fluid-secretion rate by any cyclic nucleotide was approximately double the unstimulated (control) rate. Tubules stimulated to less than maximal FSR by one cyclic nucleotide could be stimulated maximally by an appropriate concentration of another cyclic nucleotide. Malpighian tubules bathed in solutions that contained either[3H]cAMP or [3H]cGMP accumulated radioactivity to a level many times that in the medium. Accumulation of radioactivity by tubules bathed in 430 nmol l-1 [3H]cAMP was suppressed by 1 mmol l-1 non-radioactive cyclic nucleotides in the order cAMP>>cGMP>cIMP>cCMP; neither cTMP nor cUMP suppressed the accumulation of [3H]cAMP. Approximately 35 % of the[3H]cAMP and 80 % of the [3H]cGMP that entered the Malpighian tubule cells was metabolised to compounds that were not identified. It was concluded that cyclic nucleotides enter the Malpighian tubule cells by at least one transport mechanism which is particularly sensitive to purine-based nucleotides.

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39

Aldritt, S. M., P. Tien i C. C. Wang. "Pyrimidine salvage in Giardia lamblia." Journal of Experimental Medicine 161, nr 3 (1.03.1985): 437–45. http://dx.doi.org/10.1084/jem.161.3.437.

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We have found that the anaerobic protozoan parasite Giardia lamblia is incapable of de novo pyrimidine metabolism, as shown by its inability to incorporate orotate, bicarbonate, and aspartate into the pyrimidine nucleotide pool. Results from high performance liquid chromatography of pyrimidine and pyrimidine nucleoside pulse-labeled nucleotide pools and enzyme assays suggest that the parasite satisfies its pyrimidine nucleotide needs predominantly through salvage of uracil by a cytoplasmic uracil phosphoribosyltransferase. Exogenous uridine and cytidine are primarily converted to uracil by the action of uridine hydrolase and cytidine deaminase before incorporation into nucleotide pools. Direct salvage of cytosine occurs to a relatively limited extent via cytosine phosphoribosyltransferase. G. lamblia relies on salvage of exogenous thymidine for ribosylthymine monophosphate (TMP) synthesis, accomplished primarily through the action of a 100,000 g-pelletable thymidine phosphotransferase.

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40

Kitten, A. M., J. C. Lee i M. S. Olson. "Osteogenic protein-1 enhances phenotypic expression in ROS 17/2.8 cells". American Journal of Physiology-Endocrinology and Metabolism 269, nr 5 (1.11.1995): E918—E926. http://dx.doi.org/10.1152/ajpendo.1995.269.5.e918.

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Osteogenic protein-1 (OP-1) stimulates bone morphogenesis in vivo and modulates osteoblast growth and differentiation in vitro. Treatment of ROS 17/2.8 cells with OP-1 resulted in a time- and concentration-dependent inhibition of [3H]thymidine incorporation. In contrast, OP-1 treatment stimulated phenotypic differentiation in ROS 17/2.8 cells, as indicated by enhanced 1) alkaline phosphatase activity (4-fold); 2) alkaline phosphatase mRNA (5-fold); 3) parathyroid hormone receptor mRNA (2-fold), and 4) parathyroid hormone-stimulated adenosine 3',5'-cyclic monophosphate accumulation (2-fold). OP-1-induced changes in cell growth and gene expression were sensitive to cycloheximide and actinomycin D. Measurement of [3H]thymidine incorporation and alkaline phosphatase activity in situ revealed heterogeneity in the cellular responses to OP-1. Proliferating cells exhibited less alkaline phosphatase activity than nonproliferating cells, whereas cells expressing high levels of alkaline phosphatase incorporated little [3H]thymidine. Our data delineating the responses of mature differentiated osteoblasts to OP-1 suggest that potentiation of osteoblast differentiated function is an important component of bone morphogenesis in vivo.

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41

Ikeda, U., K. Okada, S. Ishikawa, T. Saito, T. Kasahara i K. Shimada. "Monocyte chemoattractant protein 1 inhibits growth of rat vascular smooth muscle cells". American Journal of Physiology-Heart and Circulatory Physiology 268, nr 3 (1.03.1995): H1021—H1026. http://dx.doi.org/10.1152/ajpheart.1995.268.3.h1021.

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The early atherosclerotic lesion is characterized by the migration of inflammatory cells, including monocytes, which may serve as a source of cytokines such as monocyte chemoattractant protein 1 (MCP-1), a homologue of mouse JE. We investigated the effect of MCP-1 on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortae. In Northern blot analysis, MCP-1/JE transcripts were not observed in unstimulated VSMC, but its expression was clearly observed by exposure to lipopolysaccharide (1 micrograms/ml) for 6 h. Human recombinant MCP-1 inhibited the uptake of [3H]thymidine by VSMC cultured in 0.5% fetal bovine serum (FBS) containing Dulbecco's modified Eagle's medium (DMEM) in a dose-dependent manner. The inhibitory effect of MCP-1 on the growth of VSMC was also confirmed by a change in cell counts. The antiproliferative effect of MCP-1 was significantly blocked in the presence of an anti-MCP-1 antibody. MCP-1-induced inhibition of [3H]thymidine uptake was not affected in the presence of indomethacin (1 micrograms/ml) or NG-monomethyl-L-arginine (0.1 mM), and MCP-1 showed no effect on 6-ketoprostaglandin F1 alpha, guanosine 3',5'-cyclic monophosphate, and adenosine 3',5'-cyclic monophosphate syntheses in VSMC. These results indicate that MCP-1 inhibits the proliferation of VSMC in vitro and that its effect is independent of prostaglandin or nitric oxide generation.

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Gustafson, Erik A., Raymond F. Schinazi i Joyce D. Fingeroth. "Human Herpesvirus 8 Open Reading Frame 21 Is a Thymidine and Thymidylate Kinase of Narrow Substrate Specificity That Efficiently Phosphorylates Zidovudine but Not Ganciclovir". Journal of Virology 74, nr 2 (15.01.2000): 684–92. http://dx.doi.org/10.1128/jvi.74.2.684-692.2000.

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ABSTRACT Human herpesvirus 8 (HHV8) open reading frame (ORF) 21 is predicted to encode a protein similar to the thymidine kinase (TK) enzyme of other herpesviruses. Expressed in mammalian cells, ORF 21 was found to have low TK activity, based on poor growth in media containing hypoxanthine-aminopterin-thymidine (HAT) and low incorporation of [3H]thymidine into high-molecular-weight DNA. Kinetic analysis using HHV8 TK as a purified glutathioneS-transferase (GST) fusion protein showed that the enzyme has a comparatively high Km for thymidine (dThd) of ∼33.2 μM. Nearly 50% of the phosphorylated product of the reaction with dThd was thymidylate. This monophosphate kinase activity was more pronounced with 3′-azido-3′-deoxythymidine (AZT), in which 78% of the reaction product was AZT diphosphate. Thymidine analogs competitively inhibited dThd phosphorylation by HHV8 TK, while 2′-deoxyguanosine, 2′-deoxyadenosine, 2′-deoxycytidine, and corresponding analogs did not. Further competition experiments revealed that the nucleoside analog ganciclovir (GCV), at up to 1,000-fold molar excess, could not significantly inhibit dThd phosphorylation by the enzyme. In support of these data, 143B TK− cells expressing HHV8 TK phosphorylated GCV very poorly and were not susceptible to GCV toxicity compared to parental cells. Phosphorylation of [3H]GCV by a purified GST-HHV8 TK fusion protein was not detected by high-pressure liquid chromatography analysis. Structural features of HHV8 TK substrate recognition were investigated. Therapeutic implications of these findings are discussed.

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Sameer Chitre, Trupti, Kalyani Dhirendra Asgaonkar, Shital Manoj Patil, Muthu Kumaradoss Kathiravan i Subhash Balkrishna Padhye. "Exploring Pyrimidine Pharmacophore as Thymidine Monophosphate Kinase Inhibitors for Antitubercular Activity: A Review". Current Topics in Medicinal Chemistry 16, nr 28 (26.09.2016): 3211–23. http://dx.doi.org/10.2174/1568026616666160506130914.

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Van Calenbergh, S., S. Pochet i H. Munier-Lehmann. "Drug Design and Identification of Potent Leads Against Mycobacterium tuberculosis Thymidine Monophosphate Kinase". Current Topics in Medicinal Chemistry 12, nr 7 (1.03.2012): 694–705. http://dx.doi.org/10.2174/156802612799984580.

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Byun, Youngjoo, Susan R. Vogel, Andrew J. Phipps, Cecilia Carnrot, Staffan Eriksson, Rohit Tiwari i Werner Tjarks. "Synthesis and Biological Evaluation of Inhibitors of Thymidine Monophosphate Kinase from Bacillus Anthracis". Nucleosides, Nucleotides and Nucleic Acids 27, nr 3 (8.02.2008): 244–60. http://dx.doi.org/10.1080/15257770701845238.

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Ogawa, Aoba, Gen-ichi Sampei i Gota Kawai. "Crystal structure of the flavin-dependent thymidylate synthase Thy1 from Thermus thermophilus with an extra C-terminal domain". Acta Crystallographica Section F Structural Biology Communications 75, nr 6 (1.06.2019): 450–54. http://dx.doi.org/10.1107/s2053230x19007192.

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The thymidylate synthases ThyA and Thy1 are enzymes that catalyse the formation of thymidine monophosphate from 2′-deoxyuridine monophosphate. Thy1 (or ThyX) requires flavin for catalytic reactions, while ThyA does not. In the present study, the crystal structure of the flavin-dependent thymidylate synthase Thy1 from Thermus thermophilus HB8 (TtThy1, TTHA1096) was determined in complex with FAD and phosphate at 2.5 Å resolution. TtThy1 is a tetrameric molecule like other Thy1 proteins, to which four FAD molecules are bound. In the crystal of TtThy1, two phosphate ions were bound to each dUMP-binding site. The characteristic feature of TtThy1 is the existence of an extra C-terminal domain (CTD) consisting of three α-helices and a β-strand. The function of the CTD is unknown and database analysis showed that this CTD is only shared by part of the Deinococcus–Thermus phylum.

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Weinfeld, Michael, Norman E. Gentner, Lyle D. Johnson i Malcolm C. Paterson. "Photoreversal: dependent release of thymidine and thymidine monophosphate from pyrimidine dimer containing DNA excision fragments isolated from ultraviolet-damaged human fibroblasts". Biochemistry 25, nr 9 (maj 1986): 2656–64. http://dx.doi.org/10.1021/bi00357a055.

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Zheng, Yuxiang, i Lewis C. Cantley. "Toward a better understanding of folate metabolism in health and disease". Journal of Experimental Medicine 216, nr 2 (26.12.2018): 253–66. http://dx.doi.org/10.1084/jem.20181965.

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Folate metabolism is crucial for many biochemical processes, including purine and thymidine monophosphate (dTMP) biosynthesis, mitochondrial protein translation, and methionine regeneration. These biochemical processes in turn support critical cellular functions such as cell proliferation, mitochondrial respiration, and epigenetic regulation. Not surprisingly, abnormal folate metabolism has been causally linked with a myriad of diseases. In this review, we provide a historical perspective, delve into folate chemistry that is often overlooked, and point out various missing links and underdeveloped areas in folate metabolism for future exploration.

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Xue, Ying, Wei Jin, Xian-Shun Xu, Li Yong, Bin Hu, Jing Xiong, Xue-Mei Hu, Lin-Sen Qing i Jing Xie. "Quality Evaluation of Tricholoma matsutake based on the Nucleic Acid Compounds by UPLC-TOF/MS and UPLC-QqQ/MS". Molecules 24, nr 1 (21.12.2018): 34. http://dx.doi.org/10.3390/molecules24010034.

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So far, there has been no quality evaluation of Tricholoma matsutake. Nucleic acid compounds are a kind of functional ingredient in T. matsutake that is beneficial to human health. In this study, a UPLC-TOF/MS method was first used to scan and identify the potential nucleic acid compounds in T. matsutake. Based on the calculation of the molecular formula and subsequent confirmation by authentic standards, 15 nucleic acid compounds were unambiguously identified: adenosine, cytidine, guanosine, inosine, thymidine, uridine, xanthosine dehydrate, 2′-deoxyadenosine, 2′-deoxycytidine, 2′-deoxyguanosine, 2′-deoxyuridine, adenosine 5′-monophosphate, cytidine 5′-monophosphate, guanosine 5′-monophosphate, and uridine 5′-monophosphate. Then, a UPLC-QqQ/MS method was developed for the subsequent quantitative analysis. After validating the limits of quantification, detection, precision, repeatability, and recovery through a calibration curve, the content of 15 nucleic acid compounds was determined by the proposed UPLC-QqQ/MS method in 80 T. matsutake samples collected from different regions in Sichuan province, Southwest China. After the statistical analysis, we suggest that the total content of nucleic acid compounds in the qualified T. matsutake should be higher than 24.49 mg/100 g. The results indicated that the combined use of UPLC-TOF/MS and UPLC-QqQ/MS is efficient for fast identification and determination of nucleic acid compounds to comprehensively evaluate the quality of T. matsutake.

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Ko, In Ok, Ki-Hye Jung, Mi Hyun Kim, Kyeung Jun Kang, Kyo Chul Lee, Kyeong Min Kim, Insup Noh i in. "Preliminary19F-MRS Study of Tumor Cell Proliferation with 3′-deoxy-3′-fluorothymidine and Its Metabolite (FLT-MP)". Contrast Media & Molecular Imaging 2017 (2017): 1–7. http://dx.doi.org/10.1155/2017/3981358.

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The thymidine analogue 3′-deoxy-3′-[18F]fluorothymidine, or [18F]fluorothymidine ([18F]FLT), is used to measure tumor cell proliferation with positron emission tomography (PET) imaging technology in nuclear medicine. FLT is phosphorylated by thymidine kinase 1 (TK1) and then trapped inside cells; it is not incorporated into DNA. Imaging with18F-radiolabeled FLT is a noninvasive technique to visualize cellular proliferation in tumors. However, it is difficult to distinguish between [18F]FLT and its metabolites by PET imaging, and quantification has not been attempted using current imaging methods. In this study, we successfully acquiredin vivoF19spectra of natural or nonradioactive 3′-deoxy-3′-fluorothymidine ([19F]FLT) and its monophosphate metabolite (FLT-MP) in a tumor xenograft mouse model using 9.4T magnetic resonance imaging (MRI). This preliminary result demonstrates that19F magnetic resonance spectroscopy (MRS) with FLT is suitable for thein vivoassessment of tumor aggressiveness and for early prediction of treatment response.

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