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https://www.readbyqxmd.com/read/28813597/synthesis-of-4-azido-n-acetylhexosamine-uridine-diphosphate-donors-clickable-glycosaminoglycans
#1
Xing Zhang, Dixy E Green, Victor L Schultz, Lei Lin, Xiaorui Han, Ruitong Wang, Alexander Yaksic, So Young Kim, Paul L DeAngelis, Robert J Linhardt
Unnatural chemically modified, nucleotide sugars, UDP-4-N3-GlcNAc and UDP-4-N3-GalNAc were synthesized for the first time. These unnatural UDP-sugar products were then tested for incorporation into hyaluronan, heparosan or chondroitin using polysaccharide synthases. The UDP-4-N3-GlcNAc served as a chain termination substrate for hyaluronan or heparosan synthases; a single analog was added to the non-reducing end of the sugar chain and no subsequent elongation was detected. Compared to chemical method to introduce azido groups into polysaccharides, this enzymatic technique provided a "green" approach to access regioselectively azide-functionalized GAGs, which would bring better control of the final structure and composition of these macromolecules...
August 16, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28808386/in-vitro-inhibitory-effects-of-andrographis-paniculata-gynura-procumbens-ficus-deltoidea-and-curcuma-xanthorrhiza-extracts-and-constituents-on-human-liver-glucuronidation-activity
#2
Zulhilmi Husni, Sabariah Ismail, Mohd Halimhilmi Zulkiffli, Atiqah Afandi, Munirah Haron
BACKGROUND: Andrographis paniculata, Gynura procumbens, Ficus deltoidea and Curcuma xanthorrhiza are commonly consumed as herbal medicines. However their effects on human liver glucuronidation activity are not yet evaluated. OBJECTIVE: In this study, we evaluate the inhibitory Effects of Andrographis paniculata, Gynura procumbens, Ficus deltoidea and Curcuma xanthorrhiza extracts and their constituents on human liver glucuronidation activity. MATERIALS AND METHODS: Herbal extracts (aqueous, methanolic and ethanolic extracts) and their constituents were incubated with human liver microsomes with the addition of UDPGA to initiate the reaction...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28807888/spectroscopic-and-calorimetric-assays-reveal-dependence-on-dctp-and-two-metals-zn-2-mg-2-for-enzymatic-activity-of-schistosoma-mansoni-deoxycytidylate-dcmp-deaminase
#3
Jéssica Fernandes Scortecci, Vitor Hugo Balasco Serrão, Juliana Cheleski, Juliana Roberta Torini, Larissa Romanello, Ricardo DeMarco, Humberto D'Muniz Pereira
The parasite Schistosoma mansoni possess all pathways for pyrimidine biosynthesis, whereby deaminases play an essential role in the thymidylate cycle, a crucial step to controlling the ratio between cytidine and uridine nucleotides. In this study, we heterologously expressed and purified the deoxycytidylate (dCMP) deaminase from S. mansoni to obtain structural, biochemical and kinetic information. Small-angle X-ray scattering of this enzyme showed that it is organized as a hexamer in solution. Isothermal titration calorimetry was used to determine the kinetic constants for dCMP-dUMP conversion and the role of dCTP and dTTP in enzymatic regulation...
August 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28802260/the-essential-functions-of-krepb4-are-developmentally-distinct-and-required-for-endonuclease-association-with-editosomes
#4
Suzanne M McDermott, Kenneth Stuart
Uridine insertion and deletion RNA editing generates functional mitochondrial mRNAs in Trypanosoma brucei, and several transcripts are differentially edited in bloodstream (BF) and procyclic form (PF) cells correlating with changes in mitochondrial function. Editing is catalyzed by three ∼20S editosomes that have a common set of 12 proteins, but are typified by mutually exclusive RNase III KREN1, N2, and N3 endonucleases with distinct cleavage specificities. KREPB4 is a common editosome protein that has a degenerate RNase III domain lacking conserved catalytic residues, in addition to zinc-finger and Pumilio/fem-3 mRNA binding factor (PUF) motifs...
August 11, 2017: RNA
https://www.readbyqxmd.com/read/28798140/the-hemoglobin-homolog-cytoglobin-in-smooth-muscle-inhibits-apoptosis-and-regulates-vascular-remodeling
#5
Frances L Jourd'heuil, Haiyan Xu, Timothy Reilly, Keneta McKellar, Chaymae El Alaoui, Julia Steppich, Yong Feng Liu, Wen Zhao, Roman Ginnan, David Conti, Reynold Lopez-Soler, Arif Asif, Rebecca K Keller, John J Schwarz, Le Thi Thanh Thuy, Norifumi Kawada, Xiaochun Long, Harold A Singer, David Jourd'heuil
OBJECTIVE: The role of hemoglobin and myoglobin in the cardiovascular system is well established, yet other globins in this context are poorly characterized. Here, we examined the expression and function of cytoglobin (CYGB) during vascular injury. APPROACH AND RESULTS: We characterized CYGB content in intact vessels and primary vascular smooth muscle (VSM) cells and used 2 different vascular injury models to examine the functional significance of CYGB in vivo. We found that CYGB was strongly expressed in medial arterial VSM and human veins...
August 10, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28791744/assessment-of-the-imprinting-efficiency-of-an-imide-with-a-stoichiometric-pyridine-based-functional-monomer-in-precipitation-polymerisation
#6
K Fremielle Lim, Andrew J Hall, Stefania Lettieri, Clovia I Holdsworth
The efficiency of the stoichiometric non-covalent imprinting of the imide 2,3,5-tri-O-acetyluridine (TAU) with 2,6-bis(acrylamido)pyridine (BAAPy) as functional monomer due to their strong donor-acceptor-donor/acceptor-donor-acceptor (DAD/ADA) hydrogen bond array interaction has been evaluated by bulk imprinting. This study is the first to investigate the imprinting and template rebinding efficiencies of the TAU/BAAPy molecularly imprinted polymeric (MIP) system prepared by precipitation polymerisation. We found that the stoichiometric 1:1 T:FM ratio has not been maintained in precipitation polymerisation and an optimal TAU:BAAPy ratio of 1:2...
August 9, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28790862/hyperbilirubinemia-in-atazanavir-treated-hiv-infected-patients-the-impact-of-the-ugt1a1-28-allele
#7
REVIEW
Periklis Panagopoulos, Efstathios Maltezos, Angelos Hatzakis, Dimitrios Paraskevis
Combination antiretroviral treatment (cART) has significantly improved the life expectancy of people living with HIV. The life-long nature of cART increases the risk of side effects, which in some cases may have been caused by specific genetic characteristics. Patients treated with atazanavir (ATV) boosted with ritonavir (rit), which is a protease inhibitor used for the treatment of HIV, present with elevated bilirubin levels, at high proportions. ATV/rit-related hyperbilirubinemia has been previously associated with genetic characteristics in uridine diphosphate glucuronosyltransferase (UGT) enzyme...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28790841/relationship-between-ugt1a1-6-28-gene-polymorphisms-and-the-efficacy-and-toxicity-of-irinotecan-based-chemotherapy
#8
Yu Bai, Hai-Wei Wu, Xu Ma, Ying Liu, Yan-Hua Zhang
PURPOSE: A retrospective study was performed to analyze the relationship between uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) *6/*28 gene polymorphisms and adverse reactions associated with irinotecan (CPT-11)-based chemotherapy. The correlation between UGT1A1 polymorphisms and the clinical efficacy of CPT-11 was also analyzed, along with the influence of age and tumor type. PATIENTS AND METHODS: Patients administered a CPT-11-based regimen in the Beijing Cancer Hospital from April 2015 to September 2016 were included in our study (n=81)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28782017/generation-of-blue-chrysanthemums-by-anthocyanin-b-ring-hydroxylation-and-glucosylation-and-its-coloration-mechanism
#9
Naonobu Noda, Satoshi Yoshioka, Sanae Kishimoto, Masayoshi Nakayama, Mitsuru Douzono, Yoshikazu Tanaka, Ryutaro Aida
Various colored cultivars of ornamental flowers have been bred by hybridization and mutation breeding; however, the generation of blue flowers for major cut flower plants, such as roses, chrysanthemums, and carnations, has not been achieved by conventional breeding or genetic engineering. Most blue-hued flowers contain delphinidin-based anthocyanins; therefore, delphinidin-producing carnation, rose, and chrysanthemum flowers have been generated by overexpression of the gene encoding flavonoid 3',5'-hydroxylase (F3'5'H), the key enzyme for delphinidin biosynthesis...
July 2017: Science Advances
https://www.readbyqxmd.com/read/28780317/enzymatic-synthesis-of-ribo-and-2-deoxyribonucleosides-from-glycofuranosyl-phosphates-an-approach-to-facilitate-isotopic-labeling
#10
Wenhui Zhang, Toby Turney, Ivana Surjancev, Anthony S Serianni
Milligram quantities of α-D-ribofuranosyl 1-phosphate (sodium salt) (αR1P) were prepared by the phosphorolysis of inosine, catalyzed by purine nucleoside phosphorylase (PNPase). The αR1P was isolated by chromatography in >95% purity and characterized by (1)H and (13)C NMR spectroscopy. Aqueous solutions of αR1P were stable at pH 6.4 and 4 °C for several months. The isolated αR1P was N-glycosylated with different nitrogen bases (adenine, guanine and uracil) using PNPase or uridine phosphorylase (UPase) to give the corresponding ribonucleosides in high yield based on the glycosyl phosphate...
July 20, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28777309/biological-evaluation-of-uridine-derivatives-of-2-deoxy-sugars-as-potential-antiviral-compounds-against-influenza-a-virus
#11
Ewelina Krol, Ilona Wandzik, Martyna Krejmer-Rabalska, Boguslaw Szewczyk
Influenza virus infection is a major cause of morbidity and mortality worldwide. Due to the limited ability of currently available treatments, there is an urgent need for new anti-influenza drugs with broad spectrum protection. We have previously shown that two 2-deoxy sugar derivatives of uridine (designated IW3 and IW7) targeting the glycan processing steps during maturation of viral glycoproteins show good anti-influenza virus activity and may be a promising alternative approach for the development of new anti-influenza therapy...
August 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28775288/a-polypeptide-from-the-junction-region-sequence-of-ews-fli1-inhibits-ewing-s-sarcoma-cells-interacts-with-the-ews-fli1-and-partner-proteins
#12
Krishna Priya Thangaretnam, Gopal Gopisetty, Priya Ramanathan, Thangarajan Rajkumar
The EWS-FLI1 chimeric protein uniquely expressed in Ewing's sarcoma has an obligate role in its aetiology. In our previous report we showed that ectopic expression of the DNA sequences form the junction region (a.a 251-280) can inhibit Ewing's sarcoma cell growth. In the present report, we introduced a peptide (TAT/NLS/EWS-PEP) comprising of thirty amino acids spanning the junction in conjunction with HIV-1-trans-activating (TAT) and nuclear localization signal sequence (NLS). Peptide uptake and localization studies revealed presence of peptide in ~99% of transduced cells and in the nucleus...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28775286/elp3-and-dph3-of-schizosaccharomyces-pombe-mediate-cellular-stress-responses-through-trna-lys-uuu-modifications
#13
Desirée Villahermosa, Oliver Fleck
Efficient protein synthesis in eukaryotes requires diphthamide modification of translation elongation factor eEF2 and wobble uridine modifications of tRNAs. In higher eukaryotes, these processes are important for preventing neurological and developmental defects and cancer. In this study, we used Schizosaccharomyces pombe as a model to analyse mutants defective in eEF2 modification (dph1Δ), in tRNA modifications (elp3Δ), or both (dph3Δ) for sensitivity to cytotoxic agents and thermal stress. The dph3Δ and elp3Δ mutants were sensitive to a range of drugs and had growth defects at low temperature...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768728/extracellular-micrornas-induce-potent-innate-immune-responses-via-tlr7-myd88-dependent-mechanisms
#14
Yan Feng, Lin Zou, Dan Yan, Hongliang Chen, Ganqiong Xu, Wenling Jian, Ping Cui, Wei Chao
Tissue ischemia, such as transient myocardial ischemia, leads to release of cellular RNA including microRNA(miRNA) into the circulation and extracellular (ex-) space, but the biological function of the ex-RNA is poorly understood. We recently reported that cardiac RNA of both human and rodent origins induced cytokine production and immune cell activation. However, the identity of the ex-RNA responsible for the proinflammatory effect remains unclear. In the current study, using an miRNA array, we profiled the plasma miRNAs 4 h after transient myocardial ischemia (45 min) or sham procedure...
August 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28762967/multi-temperature-study-of-potassium-uridine-5-monophosphate-electron-density-distribution-and-anharmonic-motion-modelling
#15
Katarzyna N Jarzembska, Katarzyna Řlepokura, Radosław Kamiński, Matthias J Gutmann, Paulina M Dominiak, Krzysztof Woźniak
Uridine, a nucleoside formed of a uracil fragment attached to a ribose ring via a β-N1-glycosidic bond, is one of the four basic components of ribonucleic acid. Here a new anhydrous structure and experimental charge density distribution analysis of a uridine-5'-monophosphate potassium salt, K(UMPH), is reported. The studied case constitutes the very first structure of a 5'-nucleotide potassium salt according to the Cambridge Structural Database. The excellent crystal quality allowed the collection of charge density data at various temperatures, i...
August 1, 2017: Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials
https://www.readbyqxmd.com/read/28760958/two-interacting-ppr-proteins-are-major-arabidopsis-editing-factors-in-plastid-and-mitochondria
#16
Damien Guillaumot, Mauricio Lopez-Obando, Kevin Baudry, Alexandra Avon, Guillem Rigaill, Andéol Falcon de Longevialle, Benjamin Broche, Mizuki Takenaka, Richard Berthomé, Geert De Jaeger, Etienne Delannoy, Claire Lurin
RNA editing is converting hundreds of cytosines into uridines during organelle gene expression of land plants. The pentatricopeptide repeat (PPR) proteins are at the core of this posttranscriptional RNA modification. Even if a PPR protein defines the editing site, a DYW domain of the same or another PPR protein is believed to catalyze the deamination. To give insight into the organelle RNA editosome, we performed tandem affinity purification of the plastidial CHLOROPLAST BIOGENESIS 19 (CLB19) PPR editing factor...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28759864/characterization-of-the-phase-i-and-phase-ii-metabolic-profile-of-tolvaptan-by-in-vitro-studies-and-liquid-chromatography-mass-spectrometry-profiling-relevance-to-doping-control-analysis
#17
Monica Mazzarino, Valeria Buccilli, Xavier de la Torre, Ilaria Fiacco, Amelia Palermo, Daniele Ughi, Francesco Botrè
Phase I and phase II biochemical reactions involved in the biotransformation pathways of tolvaptan were characterized by LC-MS-based techniques and in vitro models to identify the most appropriate marker(s) of intake. The effects of physiological and non-physiological factors on the metabolic profile of tolvaptan were also evaluated. In vitro approaches were based on the use of pooled human liver microsomes and recombinant isoforms of cytochrome P450 and uridine diphospho glucuronosyl-transferase. Sample preparation included liquid/liquid extraction at neutral pH with tert-butyl methyl-ether...
July 14, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28756861/immobilization-stabilization-of-a-complex-multimeric-sucrose-synthase-from-nitrosomonas-europaea-synthesis-of-udp-glucose
#18
Alejandro H Orrego, Lara Trobo-Maseda, Javier Rocha-Martin, Jose M Guisan
Sucrose synthases (SuSys) can be used to synthesize cost-effective uridine 5'-diphosphate glucose (UDP-glc) or can be coupled to glycosyltransferases (GTs) for the continuous recycling of UDP-glc. In this study, we present the first report of the immobilization-stabilization of a SuSy by multipoint covalent attachment. This stabilization strategy is very complex for multimeric enzymes because a very intense multipoint attachment can promote a dramatic loss of activity and/or stability. The homotetrameric SuSy from Nitrosomonas europaea (SuSyNe) was immobilized on a glyoxyl agarose support through two different orientations...
October 2017: Enzyme and Microbial Technology
https://www.readbyqxmd.com/read/28751862/utp-gated-signaling-pathways-of-5-ht-release-from-bon-cells-as-a-model-of-human-enterochromaffin-cells
#19
Andromeda Liñán-Rico, Fernando Ochoa-Cortes, Alix Zuleta-Alarcon, Mazin Alhaj, Esmerina Tili, Josh Enneking, Alan Harzman, Iveta Grants, Sergio Bergese, Fievos L Christofi
Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to trigger or modulate gut neural reflexes and transmit information about visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms modulating Ca(2+)-dependent 5-HT release are not understood. Previous studies indicated that purinergic signaling via ATP and ADP is an important mechanism in modulation of 5-HT release. However, EC cells also respond to UTP and UDP suggesting uridine triphosphate receptor and signaling pathways are involved as well...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28746172/a-genetic-variant-in-the-catechol-o-methyl-transferase-comt-gene-is-related-to-age-dependent-differences-in-the-therapeutic-effect-of-calcium-channel-blockers
#20
Jiayue Xu, Adrian E Boström, Mohamed Saeed, Raghvendra K Dubey, Gérard Waeber, Peter Vollenweider, Pedro Marques-Vidal, Jessica Mwinyi, Helgi B Schiöth
Hypertension is the leading risk factor for cardiovascular disease and one of the major health concerns worldwide. Genetic factors impact both the risk for hypertension and the therapeutic effect of antihypertensive drugs. Sex- and age-specific variances in the prevalence of hypertension are partly induced by estrogen. We investigated 6 single nucleotide polymorphisms in genes encoding enzymes involved in estrogen metabolism in relation to sex- and age-specific differences in the systolic and diastolic blood pressure (SBP and DBP) outcome under the treatment of diuretics, calcium-channel blockers (CCBs), angiotensin-converting-enzyme inhibitors, and angiotensin-receptor blockers (ARBs)...
July 2017: Medicine (Baltimore)
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