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Inosine induces acute hyperuricaemia in rhesus monkey (Macaca mulatta) as a potential disease animal model.

Dong-Hong Tang, Chen-Yun Wang, Xi Huang, Hong-Kun Yi, Zhe-Li Li, Kai-Li Ma, You-Song Ye, Jian-Wen Zhang,

<h4>Context</h4>The uric acid metabolism pathway is more similar in primates and humans than in rodents. However, there are no reports of using primates to establish animal models of hyperuricaemia (HUA).<h4>Objectives</h4>To establish an animal model highly related to HUA in humans.<h4>Materials and methods</h4>Inosine (75, 100 and 200 mg/kg) was intraperitoneally administered to ... Read more >>

Pharm Biol (Pharmaceutical biology)
[2021, 59(1):175-182]

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Mechanism of DNA Interaction and Translocation by the Replicase of a Circular Rep-Encoding Single-Stranded DNA Virus.

Elvira Tarasova, Sonali Dhindwal, Matthew Popp, Sakeenah Hussain, Reza Khayat,

Circular Rep-encoding single-stranded DNA (CRESS-DNA) viruses infect members from all three domains of life (<i>Archaea</i>, <i>Prokarya</i>, and <i>Eukarya</i>). The replicase (Rep) from these viruses is responsible for initiating rolling circle replication (RCR) of their genomes. Rep is a multifunctional enzyme responsible for nicking and ligating ssDNA and unwinding double-stranded DNA ... Read more >>

mBio (mBio)
[2021, :e0076321]

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Concordance of human equilibrative nucleoside transporter-1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trial.

Yukiyasu Okamura, Narikazu Boku, Paula Ghaneh, William Greenhalf, Satoru Yasukawa, Hiroto Narimatsu, Akira Fukutomi, Masaru Konishi, Soichiro Morinaga, Hirochika Toyama, Atsuyuki Maeda, Yasuhiro Shimizu, Shoji Nakamori, Naohiro Sata, Keisuke Yamakita, Amane Takahashi, Wataru Takayama, Ryuzo Yamaguchi, Moriaki Tomikawa, Akio Yanagisawa, John P Neoptolemos, Katsuhiko Uesaka,

<h4>Background</h4>Expression of human equilibrative nucleoside transporter-1 (hENT1) is reported to predict survival of gemcitabine (GEM)-treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120.<h4>Aim</h4>We aimed to investigate the concordance of immunohistochemical hENT1 expression between the two antibodies and prognosis.<h4>Methods</h4>The subjects of this ... Read more >>

Cancer Rep (Hoboken) (Cancer reports (Hoboken, N.J.))
[2021, :e1507]

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In silico strategies for modeling RNA aptamers and predicting binding sites of their molecular targets.

Alejandro Escamilla-Gutiérrez, Rosa María Ribas-Aparicio, María Guadalupe Córdova-Espinoza, Juan Arturo Castelán-Vega,

RNA aptamers are single-stranded nucleic acids of 20-100 nucleotides, with high sensitivity and specificity against particular molecular targets. <i>In vitro</i> production and selection of aptamers can be performed using the SELEX method. However, this procedure requires considerable time and cost. In this sense, bioinformatics tools play an important role in ... Read more >>

Nucleosides Nucleotides Nucleic Acids (Nucleosides, nucleotides & nucleic acids)
[2021, :1-10]

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Differential Inhibition of Equilibrative Nucleoside Transporter 1 (ENT1) Activity by Tyrosine Kinase Inhibitors.

Elodie Jouan, Amélie Moreau, Arnaud Bruyere, Karima Alim, Claire Denizot, Yannick Parmentier, Olivier Fardel,

<h4>Background and objectives</h4>Equilibrative nucleoside transporter (ENT) 1 is a widely-expressed drug transporter, handling nucleoside analogues as well as endogenous nucleosides. ENT1 has been postulated to be inhibited by some marketed tyrosine kinase inhibitors (TKIs). To obtain insights into this point, the interactions of 24 TKIs with ENT1 activity have been ... Read more >>

Eur J Drug Metab Pharmacokinet (European journal of drug metabolism and pharmacokinetics)
[2021, :]

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Long non-coding RNA AGAP2-AS1 is up regulated in colorectal cancer.

Tayyebeh Ghasemi, Mohammad Khalaj-Kondori, Mohammad Ali Hosseinpour Feizi, Parviz Asadi,

Accumulating evidence has indicated that, aberrant lncRNA expression plays essential roles in the colorectal cancer (CRC) tumorigenesis. <i>AGAP2-AS1</i> is upregulated in some cancers, however, its involvement in the CRC tumorigenesis in the population of North-West of Iran has remained unknown. In this study, we evaluated its deregulation in CRC microarray ... Read more >>

Nucleosides Nucleotides Nucleic Acids (Nucleosides, nucleotides & nucleic acids)
[2021, :1-16]

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rs73092672 allele T is significantly associated with the higher risk of breast cancer incidence.

Andisheh Oroujalian, Maryam Peymani, Kamran Ghaedi,

Breast cancer is the most common cancer in women worldwide with remarkable proportion of the patients in advanced stage. Recently the importance of genetic mutations in cancers are well established and also the role of tumor suppressor genes such as <i>FHIT</i> gene in both heritable and non-heritable cancer. MicroRNAs are ... Read more >>

Nucleosides Nucleotides Nucleic Acids (Nucleosides, nucleotides & nucleic acids)
[2021, :1-11]

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Human microRNA hsa-miR-15b-5p targets the RNA template component of the RNA-dependent RNA polymerase structure in severe acute respiratory syndrome coronavirus 2.

Akira Sato, Yoko Ogino, Sei-Ichi Tanuma, Fumiaki Uchiumi,

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic of the coronavirus disease in 2019. RNA-dependent RNA polymerase (RdRp) plays an essential role in RNA replication and transcription in SARS-CoV-2. In this study, we focused on the RNA template component of viral RdRp structure and analyzed human microRNAs (miRNAs) ... Read more >>

Nucleosides Nucleotides Nucleic Acids (Nucleosides, nucleotides & nucleic acids)
[2021, :1-8]

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HMGA2 rs968697 T > C polymorphism is associated with the risk of colorectal cancer.

Xueren Gao, Xiaoting Wang,

A genetic polymorphism (rs968697 T > C) in the <i>HMGA2</i> gene has recently been linked to an increased risk of hepatoblastoma. However, no studies have been conducted to investigate the effect of the polymorphism on the risk of colorectal cancer (CRC). The study aimed to explore whether the rs968697 polymorphism had a ... Read more >>

Nucleosides Nucleotides Nucleic Acids (Nucleosides, nucleotides & nucleic acids)
[2021, :1-8]

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Novel fleximer pyrazole-containing adenosine analogues: chemical, enzymatic and highly efficient biotechnological synthesis.

Anastasia Khandazhinskaya, Barbara Eletskaya, Ilja Fateev, Maria Kharitonova, Irina Konstantinova, Vladimir Barai, Alex Azhayev, Mervi T Hyvonen, Tuomo A Keinanen, Sergey Kochetkov, Katherine Seley-Radtke, Alex Khomutov, Elena Matyugina,

Nucleoside analogues have long served as key chemotherapeutic drugs for the treatment of viral infections and cancers. Problems associated with the development of drug resistance have led to a search for the design of nucleosides capable of bypassing point mutations in the target enzyme's binding site. As a possible answer ... Read more >>

Org Biomol Chem (Organic & biomolecular chemistry)
[2021, :]

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Large-scale ratcheting in a bacterial DEAH/RHA-type RNA helicase that modulates antibiotics susceptibility.

Lena M Grass, Jan Wollenhaupt, Tatjana Barthel, Iwan Parfentev, Henning Urlaub, Bernhard Loll, Eberhard Klauck, Haike Antelmann, Markus C Wahl,

Many bacteria harbor RNA-dependent nucleoside-triphosphatases of the DEAH/RHA family, whose molecular mechanisms and cellular functions are poorly understood. Here, we show that the <i>Escherichia coli</i> DEAH/RHA protein, HrpA, is an ATP-dependent 3 to 5' RNA helicase and that the RNA helicase activity of HrpA influences bacterial survival under antibiotics treatment. ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2021, 118(30):]

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Biochemical profiling of anti-HIV prodrug Elsulfavirine (Elpida®) and its active form VM1500A against a panel of twelve human carbonic anhydrase isoforms.

Claudiu T Supuran, Alessio Nocentini, Elena Yakubova, Nikolay Savchuk, Stanislav Kalinin, Mikhail Krasavin,

The non-nucleoside reverse transcriptase inhibitor VM1500A is approved for the treatment of HIV/AIDS in its <i>N</i>-acyl sulphonamide prodrug form elsulfavirine (Elpida<sup>®</sup>). Biochemical profiling against twelve human carbonic anhydrase (CA, EC 4.2.1.1) isoforms showed that while elsulfavirine was a weak inhibitor of all isoforms, VM1500A potently and selectively inhibited human (h) ... Read more >>

J Enzyme Inhib Med Chem (Journal of enzyme inhibition and medicinal chemistry)
[2021, 36(1):1056-1060]

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Design and synthesis of novel 5-alkynyl pyrimidine nucleosides derivatives: Influence of C-6-substituent on antituberculosis activity.

Alexander N Volov, Nikolai A Volov, Yana B Platonova,

We herein report new 5-substituted uridine derivatives as potent inhibitors of mycobacteria - causative agents of tuberculosis. A series of new 5-alkynyl-substituted uridine derivatives were synthesised via palladium-catalysed Sonogashira cross-coupling reaction of 5-iodo-6-methylpyrimidine base with terminal acetylenes with good yields in DMF at room temperature. It was found that methyl ... Read more >>

Bioorg Med Chem Lett (Bioorganic & medicinal chemistry letters)
[2021, 48:128261]

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The ribosome epitranscriptome: Inert - or a platform for functional plasticity?

Joseph M Georgeson, Schraga Schwartz,

A universal property of all rRNAs explored to date is the prevalence of post-transcriptional ('epitranscriptional') modifications, which expand the chemical and topological properties of the four standard nucleosides. Are these modifications an inert, constitutive part of the ribosome? Or could they, in part, also regulate the structure or function of ... Read more >>

RNA (RNA (New York, N.Y.))
[2021, :]

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Synthesis and Structure Elucidation of the Human tRNA Nucleoside Mannosyl-Queuosine

Markus Hillmeier, Mirko Wagner, Timm Ensfelder, Eva Korytiakova, Peter Thumbs, Markus Müller, Thomas Carell,

Queuosine (Q) is a structurally complex, non-canonical RNA nucleoside. It is present in many eukaryotic and bacterial species, where it is part of the anticodon loop of certain tRNAs. In higher vertebrates, including humans, two further modified queuosine-derivatives exist - galactosyl-(galQ) and mannosyl-queuosine (manQ). The function of these low abundant ... Read more >>

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An active RNA transport mechanism into plant vacuoles

BE Floyd, Kazibwe, SC Morriss, Mugume, AY Liu, Ridout, Luo, GC MacIntosh, DC Bassham,

RNA degradation inside the plant vacuole by the ribonuclease RNS2 is essential for maintaining nucleotide concentrations and cellular homeostasis via the nucleotide salvage pathway. However, the mechanisms by which RNA is transported into the vacuole are not well understood. While selective macroautophagy may contribute to this transport, macroautophagy-independent transport pathways ... Read more >>

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Advancement of prodrug approaches for nucleotide antiviral agents.

Yanping Li, Bo Yang, Yanni Quan, Zhuorong Li,

Synthetic nucleoside or nucleotide analogues played a key role to the development of antiviral agents in past decades. However, low membrane permeability and insufficient cellular phosphorylation impaired the biological activity of polar nucleoside drugs because they have to penetrate the cell membrane and be phosphorylated to active metabolite in stepwise ... Read more >>

Curr Top Med Chem (Current topics in medicinal chemistry)
[2021, :]

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A review of the effects of ticagrelor on adenosine concentration and its clinical significance.

Mohammed Ahmed Akkaif, Mei Li Ng, Muhamad Ali Sk Abdul Kader, Nur Aizati Athirah Daud, Abubakar Sha'aban, Baharudin Ibrahim,

<h4>Background</h4>Ticagrelor is an oral antiplatelet drug that can reversibly bind to the platelet P2Y12 receptor. Ticagrelor is metabolized mainly by CYP3A4 and produces a rapid blood concentration-dependent platelet inhibitory effect. Unlike other P2Y12 receptor antagonists, many clinical features of ticagrelor are not related to P2Y12 receptor antagonism.<h4>Purpose</h4>This review aims to ... Read more >>

Pharmacol Rep (Pharmacological reports : PR)
[2021, :]

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Synthesis of Oligonucleotides Containing trans Mitomycin C DNA Adducts at N6 of Adenine and N2 of Guanine.

Elise Champeil, Owen Zacarias, Ana G Petrovic, Rinat Abzalimov, Padmanava Pradhan,

Mitomycin C, (MC), an antitumor drug, is a DNA alkylating agent currently used in the clinics. Inert in its native form, MC is reduced to reactive mitosenes which undergo nucleophilic attack by guanine or adenine bases in DNA to form monoadducts as well as interstrand crosslinks (ICLs). Although ICLs are ... Read more >>

Chemistry (Chemistry (Weinheim an der Bergstrasse, Germany))
[2021, :]

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Effect of Genistein Supplementation on the Progression of Neoplasms and the Level of the Modified Nucleosides in Rats With Mammary Cancer.

Karolina Banys, Joanna Giebultowicz, Marcin Sobczak, Rafal Wyrebiak, Wojciech Bielecki, Robert Wrzesien, Barbara Bobrowska-Korczak,

<h4>Background/aim</h4>The aim of the study was to assess the impact of nano-, micro-, and macro-sized-genistein on the growth and development of neoplasms in rats with mammary cancer. Additionally, the effect on the kinetics of changes (9-11-17-20 week of a rat's life) in the levels of methyl derivatives: 1-methyladenine, 3-methyladenine, 7-methylguanine, ... Read more >>

In Vivo (In vivo (Athens, Greece))
[2021, 35(4):2059-2072]

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Ribose Alters the Photochemical Properties of the Nucleobase in Thionated Nucleosides.

Mikołaj J Janicki, Corinna L Kufner, Zoe R Todd, Seohyun C Kim, Derek K O'Flaherty, Jack W Szostak, Jiří Šponer, Robert W Góra, Dimitar D Sasselov, Rafał Szabla,

Substitution of exocyclic oxygen with sulfur was shown to substantially influence the properties of RNA/DNA bases, which are crucial for prebiotic chemistry and photodynamic therapies. Upon UV irradiation, thionucleobases were shown to efficiently populate triplet excited states and can be involved in characteristic photochemistry or generation of singlet oxygen. Here, ... Read more >>

J Phys Chem Lett (The journal of physical chemistry letters)
[2021, 12(28):6707-6713]

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Pyrimidine biosynthesis inhibitors synergize with nucleoside analogs to block SARS-CoV-2 infection

David Schultz, Robert Johnson, Kasirajan Ayyanathan, Jesse Miller, Kanupriya Whig, Brinda Kamalia, Mark Dittmar, Stuart Weston, Holly Hammond, Carly Dillen, Lauren Castellana, Jae Seung Lee, Minghua Li, Emily Lee, Samuel Constant, Marc Ferrer, Christoph Thaiss, Matthew Frieman, Sara Cherry,

The ongoing COVID-19 pandemic has highlighted the dearth of approved drugs to treat viral infections, with only ∼90 FDA approved drugs against human viral pathogens. To identify drugs that can block SARS-CoV-2 replication, extensive drug screening to repurpose approved drugs is underway. Here, we screened ∼18,000 drugs for antiviral activity ... Read more >>

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Micro-flow hydrophilic interaction liquid chromatography coupled with triple quadrupole mass spectrometry detects modified nucleosides in the transfer RNA pool of cyanobacteria.

Yichao Qin, Qisheng Zhong, Ying Zhang, Xiuying Lin, Pengcheng Fu, Huan Lin,

Post-transcriptional modification of nucleosides is observed in almost all elements of RNA. Modified nucleosides finely tune the structure of RNA molecules and affect vital functions, such as the modified wobble position 34 of transfer RNAs expanding the reading preference of anticodons to codons. Recent investigations have revealed that the modification ... Read more >>

J Sep Sci (Journal of separation science)
[2021, :]

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Crystal structure and characterization of nucleoside diphosphate kinase from Vibrio cholerae.

Pragati Agnihotri, Anil Kumar Shakya, Arjun K Mishra, J Venkatesh Pratap,

Nucleoside diphosphate kinases (NDK) are ubiquitous enzymes that catalyse the transfer of the γ phosphate from nucleoside triphosphates (NTPs) to nucleoside diphosphate (NDPs), to maintain appropriate NTP levels in cells. NDKs are associated with signal transduction, cell development, proliferation, differentiation, tumor metastasis, apoptosis and motility. The critical role of NDK ... Read more >>

Biochimie (Biochimie)
[2021, 190:57-69]

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Differences between intrinsic and acquired nucleoside analogue resistance in acute myeloid leukaemia cells

Tamara Rothenburger, Dominique Thomas, Yannick Schreiber, Paul Wratil, Tamara Pflantz, Kirsten Knecht, Katie Digianantonio, Joshua Temple, Constanze Schneider, Hanna-Mari Baldauf, Katie-May McLaughlin, Florian Rothweiler, Berna Bilen, Samira Farmand, Denisa Bojkova, Rui Costa, Nerea Ferreirós, Gerd Geisslinger, Thomas Oellerich, Yong Xiong, Oliver Keppler, Mark Wass, Martin Michaelis, Jindrich Cinatl,

<h4>Summary</h4> <h4>Background</h4> SAMHD1 mediates resistance to anti-cancer nucleoside analogues, including cytarabine, decitabine, and nelarabine that are commonly used for the treatment of leukaemia, through cleavage of their triphosphorylated forms. Hence, SAMHD1 inhibitors are promising candidates for the sensitisation of leukaemia cells to nucleoside analogue-based therapy. Here, we investigated the effects ... Read more >>

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