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- Almer, Sven
(författare)
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Novel Strategies in the Thiopurine Treatment of Inflammatory Bowel Disease
- 2010
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Ingår i: Nucleosides, Nucleotides & Nucleic Acids. - : Taylor and Francis. - 1525-7770 .- 1532-2335. ; 29:04-Jun, s. 267-277
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Tidskriftsartikel (refereegranskat)abstract
- Thiopurine drugs are widely used as immunomodulatory and corticosteroid-sparing agents in inflammatory bowel disease. Despite being old drugs, a renewed research and clinical interest in their application has emerged during the last decade. The application of pharmacogenetic insights and metabolic monitoring, together with treatment strategies in combination with anti-TNF-antibodies and possibilities to modulate their metabolism, has paved the way to a omoderno use of the thiopurines. These aspects are briefly overviewed herein.
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- Andersen, Gorm, et al.
(författare)
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Catabolism of pyrimidines in yeast: A tool to understand degradation of anticancer drugs
- 2006
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Ingår i: Nucleosides, Nucleotides & Nucleic Acids. - : Informa UK Limited. - 1525-7770 .- 1532-2335. ; 25:9-11, s. 991-996
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Tidskriftsartikel (refereegranskat)abstract
- The pyrimidine catabolic pathway is of crucial importance in cancer patients because it is involved in degradation of several chemotherapeutic drugs, such as 5-fluorouracil; it also is important in plants, unicellular eukaryotes, and bacteria for the degradation of pyrimidine-based biocides/antibiotics. During the last decade we have developed a yeast species, Saccharomyces kluyveri, as a model and tool to study the genes and enzymes of the pyrimidine catabolic pathway. In this report, we studied degradation of uracil and its putative degradation products in 38 yeasts and showed that this pathway was present in the ancient yeasts but was lost approximately 100 million years ago in the S. cerevisiae lineage.
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- Björnberg, Olof, et al.
(författare)
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Ribosylurea accumulates in yeast urc4 mutants
- 2010
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Ingår i: Nucleosides, Nucleotides & Nucleic Acids. - : Informa UK Limited. - 1525-7770 .- 1532-2335. ; 29:4-6, s. 433-437
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Tidskriftsartikel (refereegranskat)abstract
- Yeast Saccharomyces (Lachancea) kluyveri urc4 mutants, unable to grow on uracil, biotransformed (14)C(2)-uracil into two labeled compounds, as detected by high performance liquid chromatography (HPLC). These two compounds could also be obtained following organic synthesis of ribosylurea. This finding demonstrates that in the URC pyrimidine degradation pathway, the opening of the uracil ring takes place when uracil is attached to the ribose moiety. Ribosylurea has not been reported in the cell metabolism before and the two observed compounds likely represent an equilibrium mixture of the pyranosyl and furanosyl forms.
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- Christoffersen, Stig, et al.
(författare)
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Nucleoside phosphorylases from clostridium perfringens in the synthesis of 2',3'-dideoxyinosine.
- 2010
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Ingår i: Nucleosides, Nucleotides & Nucleic Acids. - : Informa UK Limited. - 1525-7770 .- 1532-2335. ; 29:4-6, s. 445-448
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Tidskriftsartikel (refereegranskat)abstract
- Four Clostridium perfringens phosphorylases were subcloned, overexpressed and analyzed for their substrate specificity. DeoD(1) and PunA could use a variety of purine substrates, including an antiviral drug 2',3'-dideoxyinosine (ddI). In one-pot synthesis using Clostridium phosphorylases, 2',3'-dideoxyuridine and hypoxanthine were converted to ddI at yield of about 30%.
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- Clausen, Anders Ranegaard, et al.
(författare)
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Pasteurella multocida thymidine kinase 1 efficiently activates pyrimidine nucleoside analogs.
- 2010
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Ingår i: Nucleosides, Nucleotides & Nucleic Acids. - : Informa UK Limited. - 1525-7770 .- 1532-2335. ; 29:4-6, s. 359-362
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Tidskriftsartikel (refereegranskat)abstract
- In the Pasteurella multocida genome only one putative deoxyribonucleoside kinase encoding gene, for thymidine kinase 1 (PmTK1), was identified. The PmTK1 gene was sub-cloned into Escherichia coli KY895 and it sensitized the host towards 2',2'-difluoro-deoxycytidine (gemcitabine, dFdC), 3'-azido-thymidine (AZT) and 5-fluoro-deoxyuridine (5F-dU). PmTK1 was over-expressed and purified with two different tags. Apparently, deoxyuridine (dU), and not thymidine (dT), is the preferred substrate. We suggest that PmTK1s could be employed as a species-specific activator of uracil-based nucleoside antibiotics.
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- Clausen, Anders Ranegaard, et al.
(författare)
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Plants salvage deoxyribonucleosides in mitochondria.
- 2014
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Ingår i: Nucleosides, Nucleotides & Nucleic Acids. - : Informa UK Limited. - 1525-7770 .- 1532-2335. ; 33:4-6, s. 291-295
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Tidskriftsartikel (refereegranskat)abstract
- Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides into the corresponding 5'-monophosphate deoxyribonucleosides to supply the cell with nucleic acid precursors. In mitochondrial fractions of the model plant Arabidopsis thaliana, we detected deoxyadenosine and thymidine kinase activities, while the cytosol fraction contained six-fold lower activity and chloroplasts contained no measurable activities. In addition, a mitochondrial fraction isolated from the potato Solanum tuberosum contained thymidine kinase and deoxyadenosine kinase activities. We conclude that an active salvage of deoxyribonucleosides in plants takes place in their mitochondria. In general, the observed localization of the plant dNK activities in the mitochondrion suggests that plants have a different organization of the deoxyribonucleoside salvage compared to mammals.
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