- Alkene-tetrazine ligation for imaging cellular DNA
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5-Vinyl-2′-deoxyuridine (VdU) is the first reported metabolic probe for cellular DNA synthesis that can be visualized by using an inverse electron demand Diels-Alder reaction with a fluorescent tetrazine. VdU is incorporated by endogenous enzymes into the genomes of replicating cells, where it exhibits reduced genotoxicity compared to 5-ethynyl-2′-deoxyuridine (EdU). The VdU-tetrazine ligation reaction is rapid (k≈0.02 M-1 s -1) and chemically orthogonal to the alkyne-azide "click" reaction of EdU-modified DNA. Alkene-tetrazine ligation reactions provide the first alternative to azide-alkyne click reactions for the bioorthogonal chemical labeling of nucleic acids in cells and facilitate time-resolved, multicolor labeling of DNA synthesis. Diels-Alder on DNA: 5-Vinyl-2′-deoxyuridine (VdU) is metabolically incorporated into cellular DNA where it can be visualized by using inverse electron demand Diels-Alder reactions with fluorescent tetrazines. VdU-tetrazine ligation reactions are rapid (k≈0.02 M-1 s-1) and chemically orthogonal to alkyne-azide "click" reactions, thereby enabling time-resolved, multicolor labeling of DNA synthesis in individual cells.
- Rieder, Ulrike,Luedtke, Nathan W.
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- Synthesis of 5-[3,6-di(pyridin-2-yl)pyridazine-4-yl]-2′-deoxyuridine-5′-O-triphosphate - A potential probe for fluorescence detection and imaging DNA
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Efficient synthesis of 5-[3,6-di(pyridin-2-yl)pyridazine-4-yl]-2′-deoxyuridine-5′-O-triphosphate, a potential substrate for fluorescence detection and imaging of DNA is reported. Inverse electron demand Diels-Alder (invDA) reaction between the electron-rich 5-vinyl-2′-deoxyuridine-5′-O-triphosphate and electron-deficient tetrazine dienophile 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine resulted in the formation of 5-[3,6-di(pyridin-2-yl)pyridazine-4-yl]-2′-deoxyuridine-5′-O-triphosphate in 80% yield. This class of molecules will find applications in polymerase chain reactions for fluorescence detection and imaging applications of cellular DNA.
- Kore, Anilkumar R.,Yang, Bo,Srinivasan, Balasubramanian
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- One-pot approach to functional nucleosides possessing a fluorescent group using nucleobase-exchange reaction by thymidine phosphorylase
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Herein, we describe β-selective coupling between a modified uracil and a deoxyribose to produce functionalized nucleosides catalyzed by thymidine phosphorylase derived from Escherichia coli. This enzyme mediates nucleobase-exchange reactions to convert unnatural nucleosides possessing a large functional group such as a fluorescent molecule, coumarin or pyrene, linked via an alkyl chain at the C5 position of uracil. 5-(Coumarin-7-oxyhex-5- yn)uracil (C4U) displayed 57.2% conversion at 40% DMSO concentration in 1.0 mM phosphate buffer pH 6.8 to transfer thymidine to an unnatural nucleoside with C4U as the base. In the case of using 5-(pyren-1-methyloxyhex-5-yn)uracil (P4U) as the substrate, TP also could catalyse the reaction to generate a product with a very large functional group at 50% DMSO concentration (21.6% conversion). We carried out docking simulations using MF myPrest for the modified uracil bound to the active site of TP. The uracil moiety of the substrate binds to the active site of TP, with the fluorescent moiety linked to the C5 position of the nucleobase located outside the surface of the enzyme. As a consequence, the bulky fluorescent moiety binding to uracil has little influence on the coupling reaction.
- Hatano, Akihiko,Kurosu, Masayuki,Yonaha, Susumu,Okada, Munehiro,Uehara, Sanae
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p. 6900 - 6905
(2013/10/08)
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- PHOTORESPONSIVE NUCLEIC ACID MANUFACTURING METHOD
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The present invention provides a manufacturing method that can easily manufacture a compound known as photoresponsive (photocoupling) nucleic acids at high yield in a shorter period of time than that of the conventional technology. The present invention relates to a method of manufacturing a photoresponsive nucleic acid which includes a step of reacting a nucleic acid having groups represented by the Formula I, the Formula III, the Formula IV, or the Formula V and a compound represented by the Formula II, or reacting a nucleic acid having groups represented by the Formula VI, the Formula VIII, the Formula IX, or the Formula X and a compound represented by the Formula VII by heating them by microwaves in the presence of a metal catalyst, a basic substance, and a solvent.
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Page/Page column 20-21
(2010/12/17)
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- Detection of methylcytosine by DNA photoligation via hydrophobic interaction of the alkyl group
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We report the nonenzymatic detection of 5-methylcytosine by using template-directed photoligation through 5-vinyl-2′-deoxyuridine derivatives with high selectivity. In this paper, we propose a new detection method by using hydrophobic interaction. The photoligation yield of the 5-methylcytosine case was approximately 5.6-fold higher than that in the case of cytosine.
- Ogino, Masayuki,Taya, Yuuta,Fujimoto, Kenzo
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supporting information; experimental part
p. 3163 - 3167
(2011/02/25)
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- PALLADIUM-CATALYZED CROSS-COUPLING REACTION OF ORGANOSTANNANES WITH NUCLEOSIDE HALIDES
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A general reaction is described for the synthesis of C-5 substituted nucleosides through the coupling of organostannanes with nucleoside-palladium intermediate derived in situ from 5-iodouridine (or 5-iodo-2'-deoxyuridine) and .The reaction was used for the synthesis of C-5 aryl, heteroaryl, vinyl, allyl and alkyl substituted nucleosides.
- Hassan, Mohamed Ezeldin
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p. 1944 - 1948
(2007/10/02)
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- Synthesis of thymidine from 5-iodo-2'-deoxyuridine
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A simple, high yield synthesis of thymidine from 5-iodo-2'-deoxyuridine is described, using tetramethyltin and tetrakis(triphenylphosphine)palladium(0) in hexamethylphosphoric triamide. Likewise, 5-phenyl- and 5-vinyl-2'-deoxyuridine can be obtained, and through reduction of the latter the 5-ethyl analogue is also at hand.
- Herdewijn,Kerremans,Wigerinck,Vandendriessche,Van Aerschot
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p. 4397 - 4400
(2007/10/02)
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- Synthesis and Antiviral Activity of Phosphonoacetic and Phosphonoformic Acid Esters of 5-Bromo-2'-deoxyuridine and Related Pyrimidine Nucleosides and Acyclonucleosides
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Phosphonoacetic acid (PAA, 1) was coupled with various acyclonucleosides, 2'-deoxyuridines, cytidines, and arabinosyluracils, with 2,4,6-triisopropylbenzenesulfonyl chloride (TPS) or dicyclohexylcarbodiimide (DCCI) as condensing agents, to give a range of phosphonate esters.The carboxylic ester linkage of PAA to the 5'-position of 5-bromo-2'-deoxyuridine (BUdR, 3) was achieved via the mixed anhydride formed from (diethylphosphono)acetic acid and trifluoroacetic anhydride.Phosphonoformic acid (PFA, 2) was coupled with BUdR by using the DCCI method to give the phosphonate ester (59).Of these compounds only phosphonate esters in the 2'-deoxyuridine series showed significant activity against herpes simplex virus types 1 and 2.The BUdR-PAA derivative (7) and the BUdR-PFA derivative (59) were highly active, especially the latter, which was more active than the parent nucleoside BUdR (3) against the type 2 virus.The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agents, but an intrinsic component of antiviral activity may also be involved.
- Lambert, Robert W.,Martin, Joseph A.,Thomas, Gareth J.,Duncan, Ian B.,Hall, Michael J.,Heimer, Edgar P.
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p. 367 - 374
(2007/10/02)
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- Synthesis of 5-(1-Substituted Ethyl)uracil Derivatives and Some of their Chemical and Biological Properties
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In order to obtain compounds which give 2'-deoxy-5-vinyluridine (VdUrd) by elimination under basic conditions, a series of 5-(1-substituted ethyl)uracil derivatives has been made.Attemps to obtain 5-(1-alkyl- or -aryl-sulphonyloxy) derivatives were unsuccessful because elimination to give the 5-vinyl derivatives was extremely easy. 5-(1-acyloxyethyl) derivatives did not eliminate, but with aqueous alkali gave 5-(1-hydroxymethyl)uracil derivatives.Reaction of VdUrd with a series of arenethiols gave 5-(1-arylthioethyl)-2'-deoxyuridines.In the absence of radical inhibitors 5-(2-arylthioethyl)-2'-deoxyuridines were the major products.The arylthio compounds were oxidized to the corresponding sulphoxides and sulphones.Treatment of these 5-(1-substituted) derivatives with potassium t-butoxide in dimethylformamide gave VdUrd.As expected the reaction rate was greatest with the compound which had the best leaving group.However, with aqueous alkali the compounds gave 2'-deoxy-5-(1-hydroxyethyl)uridine and at pH 7.6 at 37 degC they were stable.When N-3 of the uracil ring was alkylated the elimination was faster.The implication of this result for the mechanism of the elimination is discussed.Two of the compounds synthesized, namely 2'-deoxy-5-uridine and 2'-deoxy-3-methyl-5-uridine showed activity against vaccinia virus and murine L1210 leukaemia cells at a concentration of 30-40 μg/ml, and 2'-deoxy-5-uridine, had activity against different strains of herpes simplex viruses types 1 and 2 at a concentration of 20 μg/ml.
- Jones, A. Stanley,McClean, Michael J.,Slater, Martin J.,Walker, Richard T.
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p. 457 - 464
(2007/10/02)
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- (E)-ALCENYL-5 DESOXY-2' URIDINES PAR COUPLAGES D'ORGANOZIRCONIENS EHTYLENIQUES AVEC L'IODO-5 O-3',5'-BIS (TRIMETHYL) DESOXYURIDINE, CATALYSES PAR COMPLEXES ORGANOPALLADIES
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(E) 5-Alkenyl 2'-deoxyuridines are obtained with moderate to high yields by the palladium catalyzed reaction of alkenylzirconium reagents with O-3',5'-bis(trimethylsilyl) deoxyuridine in T.H.F.
- Vincent, Patrice,Beaucourt, Jean-Pierre,Pichat, Louis
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