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Nucleosides, Nucleotides & Nucleic Acids

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https://www.readbyqxmd.com/read/27846376/substrate-specificity-of-e-coli-uridine-phosphorylase-further-evidences-of-high-syn-conformation-of-the-substrate-in-uridine-phosphorolysis
#1
C S Alexeev, G G Sivets, T N Safonova, S N Mikhailov
Twenty five uridine analogues have been tested and compared with uridine with respect to their potency to bind to E. coli uridine phosphorylase. The kinetic constants of the phosphorolysis reaction of uridine derivatives modified at 2'-, 3'- and 5'-positions of the sugar moiety and 2-, 4-, 5- and 6-positions of the heterocyclic base were determined. The absence of the 2'- or 5'-hydroxyl group is not crucial for the successful binding and phosphorolysis. On the other hand, the absence of both the 2'- and 5'-hydroxyl groups leads to the loss of substrate binding to the enzyme...
November 15, 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27835056/multispectroscopic-studies-on-the-interaction-of-a-copper-ii-complex-of-ibuprofen-drug-with-calf-thymus-dna
#2
Nahid Shahabadi, Farshad Shiri
The interaction of copper(II)-ibuprofenato complex with calf thymus DNA (ct-DNA) has been explored following, UV-visible spectrophotometry, fluorescence measurement, dynamic viscosity measurements, and circular dichroism spectroscopy. In spectrophotometric studies of ct-DNA it was found that [Cu(ibp)2]2 can form a complex with double-helical DNA. The association constant of [Cu(ibp)2]2 with DNA from UV-Vis study was found to be 6.19 × 10(4) L mol(-1). The values of Kf from fluorescence measurement clearly underscore the high affinity of [Cu(ibp)2]2 to DNA...
November 11, 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27831822/intermolecular-interaction-of-nickel-ii-phthalocyanine-tetrasulfonic-acid-tetrasodium-salt-with-bovine-serum-albumin-a-multi-technique-study
#3
Hamid Dezhampanah, Roghaye Firouzi, Leila Hasani
The interaction of nickel (II) phthalocyanine tetrasulfonic acid tetrasodium salt with bovine serum albumin (BSA) has been investigated by combination of fluorescence, UV-vis absorption, Fourier transform infrared (FT-IR), and circular dichorism (CD) spectroscopies as well as through molecular docking. Fluorescence quenching and absorption spectra were investigated as a mean for estimating the binding parameters. Analysis of fluorescence quenching data at different temperatures was performed in order to specify the thermodynamics parameters for interactions of phthalocyanine complex with BSA...
November 10, 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27759493/experimental-and-computational-studies-on-the-effects-of-valganciclovir-as-an-antiviral-drug-on-calf-thymus-dna
#4
Nahid Shahabadi, Mehdi Pourfoulad, Neda Hosseinpour Moghadam
DNA-binding properties of an antiviral drug, valganciclovir (valcyte) was studied by using emission, absorption, circular dichroism, viscosity, differential pulse voltammetry, fluorescence techniques, and computational studies. The drug bound to calf thymus DNA (ct-DNA) in a groove-binding mode. The calculated binding constant of UV-vis, Ka, is comparable to groove-binding drugs. Competitive fluorimetric studies with Hoechst 33258 showed that valcyte could displace the DNA-bound Hoechst 33258. The drug could not displace intercalated methylene blue from DNA double helix...
October 19, 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27759491/dna-binding-study-of-anticancer-drug-cytarabine-by-spectroscopic-and-molecular-docking-techniques
#5
Nahid Shahabadi, Monireh Falsafi, Maryam Maghsudi
The interaction of anticancer drug cytarabine with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multispectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove-binding mode, while the binding constant of UV-vis and the number of binding sites were 4.0 ± 0.2 × 10(4) L mol(-1) and 1.39, respectively. The fluorimetric studies showed that the reaction between the drugs with CT-DNA is exothermic...
October 19, 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27759481/synthesis-and-antiviral-evaluation-of-fluorinated-acyclo-nucleosides-and-their-phosphoramidates
#6
Sawsan Mahmoud, Hao Li, Tamara R McBrayer, Leda Bassit, Sherif F Hammad, Steven J Coats, Franck Amblard, Raymond F Schinazi
A novel series of tetrafluoro and hexafluoro acyclic nucleosides and their phosphoramidates were successfully prepared from commercially available 2,2,3,3-tetrafluoro-1,4-butanediol and 2,2,3,3,4,4-hexafluoro-1,5-pentanediol in four to six steps. Their ability to block HIV, HCV, HSV-1, and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte, CEM, and Vero cells was assessed.
October 19, 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27759477/equilibrative-nucleoside-transporters-a-review
#7
Rebba C Boswell-Casteel, Franklin A Hays
Equilibrative nucleoside transporters (ENTs) are polytopic integral membrane proteins that mediate the transport of nucleosides, nucleobases, and therapeutic analogs. The best-characterized ENTs are the human transporters hENT1 and hENT2. However, non-mammalian eukaryotic ENTs have also been studied (e.g., yeast, parasitic protozoa). ENTs are major pharmaceutical targets responsible for modulating the efficacy of more than 30 approved drugs. However, the molecular mechanisms and chemical determinants of ENT-mediated substrate recognition, binding, inhibition, and transport are poorly understood...
October 19, 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27754763/novel-mutation-in-hprt1-causing-a-splicing-error-with-multiple-variations
#8
Shimpei Baba, Takashi Saito, Yasukazu Yamada, Eri Takeshita, Noriko Nomura, Kenichiro Yamada, Nobuaki Wakamatsu, Masayuki Sasaki
Lesch-Nyhan disease (LND) is a rare X-linked recessive disorder caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT), encoded by the HPRT1. To date, nearly all types of mutations have been reported in the whole gene; however, duplication mutations are rare. We here report the case of a 9-month-old boy with LND. He showed developmental delay, athetosis, and dystonic posture from early infancy, but no self-injurious behaviors. Hyperuricemia was detected, and his HPRT enzyme activity in erythrocytes was completely deficient...
October 18, 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906640/a-review-of-the-implication-of-hypoxanthine-excess-in-the-physiopathology-of-lesch-nyhan-disease
#9
R J Torres, C Prior, M G Garcia, J G Puig
Lesch-Nyhan disease is caused by HGprt deficiency, however, the mechanism by which enzyme deficiency leads to the severe neurological manifestations is still unknown. We hypothesized that hypoxanthine excess leads, directly or indirectly, through its action in adenosine transport, to aberrations in neuronal development. We found that hypoxanthine diminishes adenosine transport and enhances stimulation of adenosine receptors. These effects cause an imbalance between adenosine, dopamine, and serotonin receptors in HGprt deficient cells, and cells differentiated with hypoxanthine showed an increase in dopamine, adenosine and serotonin receptors expression...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906639/ultrasonography-in-the-diagnosis-of-asymptomatic-hyperuricemia-and-gout
#10
J G Puig, L M Beltrán, C Mejía-Chew, D Tevar, R J Torres
Sonography has detected urate deposits in 34%-42% of the patients with asymptomatic hyperuricemia. This may prompt reclassification of asymptomatic hyperuricemia into "asymptomatic gout" and consideration of urate lowering therapy (ULT) to resolve urate deposits. In patients with gout and no visible tophi, sonography has detected urate deposits in half of the patients. This may allow diagnosing "tophaceous gout" and influencing the serum urate target level, prophylaxis to avoid acute gout flares during ULT, and clinical follow-up...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906638/gene-duplications-and-losses-among-vertebrate-deoxyribonucleoside-kinases-of-the-non-tk1-family
#11
Zeeshan Mutahir, Louise Slot Christiansen, Anders R Clausen, Martin W Berchtold, Zoran Gojkovic, Birgitte Munch-Petersen, Wolfgang Knecht, Jure Piškur
Deoxyribonucleoside kinases (dNKs) salvage deoxyribonucleosides (dNs) and catalyze the rate limiting step of this salvage pathway by converting dNs into corresponding monophosphate forms. These enzymes serve as an excellent model to study duplicated genes and their evolutionary history. So far, among vertebrates only four mammalian dNKs have been studied for their substrate specificity and kinetic properties. However, some vertebrates, such as fish, frogs, and birds, apparently possess a duplicated homolog of deoxycytidine kinase (dCK)...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906637/prevalence-of-urat1-allelic-variants-in-the-roma-population
#12
Blanka Stiburkova, Dana Gabrikova, Pavel Čepek, Pavel Šimek, Pavol Kristian, Elizabeth Cordoba-Lanus, Felix Claverie-Martin
The Roma represents a transnational ethnic group, with a current European population of 8-10 million. The evolutionary process that had the greatest impact on the gene pool of the Roma population is called the founder effect. Renal hypouricemia (RHUC) is a rare heterogenous inherited disorder characterized by impaired renal urate reabsorption. The affected individuals are predisposed to recurrent episodes of exercise-induced nonmyoglobinuric acute kidney injury and nephrolithiasis. To date, more than 150 patients with a loss-of-function mutation for the SLC22A12 (URAT1) gene have been found, most of whom are Asians...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906636/urat1-uox-double-knockout-mice-are-experimental-animal-models-of-renal-hypouricemia-and-exercise-induced-acute-kidney-injury
#13
Makoto Hosoyamada, Yu Tsurumi, Hidenori Hirano, Naoko H Tomioka, Yuko Sekine, Takayuki Morisaki, Shunya Uchida
Renal hypouricemia (RHUC) is a hereditary disease characterized by a low level of plasma urate but with normal urinary urate excretion. RHUC type 1 is caused by mutations of the urate transporter URAT1 gene (SLC22A12). However, the plasma urate levels of URAT1 knockout mice are no different from those of wild-type mice. In the present study, a double knockout mouse, in which the URAT1 and uricase (Uox) genes were deleted (Urat1-Uox-DKO), were used as an experimental animal model of RHUC type 1 to investigate RHUC and excise-induced acute kidney injury (EIAKI)...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906635/a-specific-inhibitor-of-lactate-dehydrogenase-overcame-the-resistance-toward-gemcitabine-in-hypoxic-mesothelioma-cells-and-modulated-the-expression-of-the-human-equilibrative-transporter-1
#14
Elisa Giovannetti, Leticia G Leon, Valentina E Gómez, Paolo A Zucali, Filippo Minutolo, Godefridus J Peters
Malignant pleural mesothelioma (MPM) is a very hypoxic malignancy, and hypoxia has been associated with resistance towards gemcitabine. The muscle-isoform of lactate dehydrogenase (LDH-A) constitutes a major checkpoint for the switch to anaerobic glycolysis. Therefore we investigated the combination of a new LDH-A inhibitor (NHI-1) with gemcitabine in MPM cell lines. Under hypoxia (O2 tension of 1%) the cell growth inhibitory effects of gemcitabine, were reduced, as demonstrated by a 5- to 10-fold increase in IC50s...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906634/extended-exposure-to-substrate-regulates-the-human-equilibrative-nucleoside-transporter-1-hent1
#15
Maliha Zafar, Zlatina Naydenova, Imogen R Coe
Human equilibrative nucleoside transporter 1 (hENT1) is a major route of entry of nucleosides and nucleoside analog drugs. The regulation of hENT1 is poorly understood in spite of its clinical importance as a drug transporter. Immunofluorescence microscopy and fluorescence-activated cell sorting suggested that cytidine pre-treatment (40 μM, 6 h) promotes hENT1 internalization in a way that does not affect either hENT1-mediated nucleoside uptake or gemcitabine-induced cytotoxicity. The Scatchard plot analyses of our NBTI binding data support previous speculations that hENT1 proteins exist as two sub-populations, and suggest that cytidine pre-treatment leads to the internalization of one population...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906633/summary-of-the-2015-purine-and-pyrimidine-society-purine-metabolic-patients-association-h-anne-simmonds-memorial-lecture
#16
Michael A Becker
No abstract text is available yet for this article.
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906632/changes-in-cardiac-nucleotide-metabolism-in-huntington-s-disease
#17
Marta Toczek, Barbara Kutryb-Zajac, Paulina Zukowska, Ewa M Slominska, Mark Isalan, Michal Mielcarek, Ryszard T Smolenski
Huntington's disease (HD) is a monogenic neurodegenerative disorder with a significant peripheral component to the disease pathology. This includes an HD-related cardiomyopathy, with an unknown pathological mechanism. In this study, we aimed to define changes in the metabolism of cardiac nucleotides using the well-established R6/2 mouse model. In particular, we focused on measuring the activity of enzymes that control ATP and other adenine nucleotides in the cardiac pool, including eNTPD, AMPD, e5'NT, ADA, and PNP...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906631/mitochondrial-purine-and-pyrimidine-metabolism-and-beyond
#18
Liya Wang
Carefully balanced deoxynucleoside triphosphate (dNTP) pools are essential for both nuclear and mitochondrial genome replication and repair. Two synthetic pathways operate in cells to produce dNTPs, e.g., the de novo and the salvage pathways. The key regulatory enzymes for de novo synthesis are ribonucleotide reductase (RNR) and thymidylate synthase (TS), and this process is considered to be cytosolic. The salvage pathway operates both in the cytosol (TK1 and dCK) and the mitochondria (TK2 and dGK). Mitochondrial dNTP pools are separated from the cytosolic ones owing to the double membrane structure of the mitochondria, and are formed by the salvage enzymes TK2 and dGK together with NMPKs and NDPK in postmitotic tissues, while in proliferating cells the mitochondrial dNTPs are mainly imported from the cytosol produced by the cytosolic pathways...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906630/evaluation-of-purine-utilization-by-lactobacillus-gasseri-strains-with-potential-to-decrease-the-absorption-of-food-derived-purines-in-the-human-intestine
#19
N Yamada, C Iwamoto, H Kano, N Yamaoka, T Fukuuchi, K Kaneko, Y Asami
It is well accepted that frequent and heavy intake of purine-rich foods causes elevation of serum uric acid levels, which is a risk factor of hyperuricemia. Reducing intestinal absorption of dietary purines may attenuate the elevation of serum uric acid levels and exacerbation of hyperuricemia. This reduction may be achieved by the ingestion of lactic acid bacteria that take up purines in the intestine. In this study, we investigated the degree of uptake and utilization of purines of three lactobacilli strains...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906629/purification-activity-and-expression-levels-of-two-uridine-cytidine-kinase-isoforms-in-neuroblastoma-cell-lines
#20
R Meinsma, A B P van Kuilenburg
Uridine-cytidine kinase (UCK) catalyzes the phosphorylation of uridine, cytidine, and several pyrimidine ribonucleoside analogs. We overexpressed and purified the two known isoforms of human UCK in Escherichia coli, produced a specific antibody against UCK1 and characterized the kinetic properties of UCK1 and 2. The Vmax of purified recombinant UCK2 was 22- and 8-fold higher with uridine and cytidine, respectively, compared to those observed for the purified recombinant UCK1 enzyme. The Km of UCK1 was 39- and 40-fold higher with uridine and cytidine, respectively, compared to those observed for the purified recombinant UCK2 enzyme...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
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