- Synthesis and characterization of Se-adenosyl-L-selenohomocysteine selenoxide
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Selenium is an essential micronutrient in humans due to the important roles of the selenocysteine-containing selenoproteins. Organoselenium metabolites are generally found to be substrates for the biochemical pathways of their sulfur analogs, and the redox chemistry of selenomethionine and some other metabolites have been previously reported. We now report the first synthesis and characterization of Se-adenosylselenohomocysteine selenoxide (SeAHO) prepared via hydrogen peroxide oxidation of Se-adenosylselenohomocysteine. The selenoxide SeAHO, in contrast to its corresponding sulfoxide S-adenosylhomocysteine (SAHO), can form hydrate, has an electrostatic interaction between the α-amino acid moiety and the highly polar selenoxide functional group, and readily oxidizes glutathione (GSH) and cysteine thiols.
- Duclos, Richard I.,Cleary, Dillon C.,Catcott, Kalli C.,Zhou, Zhaohui Sunny
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Read Online
- Discovery of a dual PRMT5-PRMT7 inhibitor
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The protein arginine methyltransferases PRMT7 and PRMT5, respectively, monomethylate and symmetrically dimethylate arginine side-chains of proteins involved in diverse cellular mechanisms, including chromatin-mediated control of gene transcription, splicing, and the RAS to ERK transduction cascade. It is believed that PRMT5 and PRMT7 act in conjunction to methylate their substrates, and genetic deletions support the notion that these enzymes derepress cell proliferation and migration in cancer. Using available structures of PRMT5, we designed DS-437, a PRMT5 inhibitor with an IC50 value of 6 μM against both PRMT5 and PRMT7 that is inactive against 29 other human protein-, DNA-, and RNA-methyltransferases and inhibits symmetrical dimethylation of PRMT5 substrates in cells. This compound behaves as a cofactor competitor and represents a valid scaffold to interrogate the potential of the PRMT5-PRMT7 axis as a target for therapy.
- Smil, David,Eram, Mohammad S.,Li, Fengling,Kennedy, Steven,Szewczyk, Magdalena M.,Brown, Peter J.,Barsyte-Lovejoy, Dalia,Arrowsmith, Cheryl H.,Vedadi, Masoud,Schapira, Matthieu
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Read Online
- Directed Evolution of a Fluorinase for Improved Fluorination Efficiency with a Non-native Substrate
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Fluorinases offer an environmentally friendly alternative for selective fluorination under mild conditions. However, their diversity is limited in nature and they have yet to be engineered through directed evolution. Herein, we report the directed evolution of the fluorinase FlA1 for improved conversion of the non-native substrate 5′-chloro-5′-deoxyadenosine (5′-ClDA) into 5′-fluoro-5′-deoxyadenosine (5′-FDA). The evolved variants, fah2081 (A279Y) and fah2114 (F213Y, A279L), were successfully applied in the radiosynthesis of 5′-[18F]FDA, with overall radiochemical conversion (RCC) more than 3-fold higher than wild-type FlA1. Kinetic studies of the two-step reaction revealed that the variants show a significantly improved kcatvalue in the conversion of 5′-ClDA into S-adenosyl-l-methionine (SAM) but a reduced kcatvalue in the conversion of SAM into 5′-FDA.
- Sun, Huihua,Yeo, Wan Lin,Lim, Yee Hwee,Chew, Xinying,Smith, Derek John,Xue, Bo,Chan, Kok Ping,Robinson, Robert C.,Robins, Edward G.,Zhao, Huimin,Ang, Ee Lui
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Read Online
- Potent SARS-CoV-2 mRNA Cap Methyltransferase Inhibitors by Bioisosteric Replacement of Methionine in SAM Cosubstrate
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Viral mRNA cap methyltransferases (MTases) are emerging targets for the development of broad-spectrum antiviral agents. In this work, we designed potential SARS-CoV-2 MTase Nsp14 and Nsp16 inhibitors by using bioisosteric substitution of the sulfonium and amino acid substructures of the cosubstrate S-adenosylmethionine (SAM), which serves as the methyl donor in the enzymatic reaction. The synthetically accessible target structures were prioritized using molecular docking. Testing of the inhibitory activity of the synthesized compounds showed nanomolar to submicromolar IC50 values for five compounds. To evaluate selectivity, enzymatic inhibition of the human glycine N-methyltransferase involved in cellular SAM/SAH ratio regulation was also determined, which indicated that the discovered compounds are nonselective inhibitors of the studied MTases with slight selectivity for Nsp16. No cytotoxic effects were observed; however, this is most likely a result of the poor cell permeability of all evaluated compounds.
- Bobi?eva, Olga,Bobrovs, Raitis,Ka?epe, Iveta,Patetko, Liene,Kalni??, Gints,?i?ovs, Mihails,Bula, Anna L.,Grī Nberga, Solveiga,Borodu??is, Mā Rti??,Ramata-Stunda, Anna,Rostoks, Nils,Jirgensons, Aigars,Tā Rs, Kaspars,Jaudzems, Kristaps
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supporting information
p. 1102 - 1107
(2021/06/30)
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- Synthesis of triazole-linked SAM-adenosine conjugates: Functionalization of adenosine at N-1 or N-6 position without protecting groups
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More than 150 RNA chemical modifications have been identified to date. Among them, methylation of adenosine at the N-6 position (m6A) is crucial for RNA metabolism, stability and other important biological events. In particular, this is the most abundant
- Atdjian, Colette,Braud, Emmanuelle,Coelho, Dylan,Ethève-Quelquejeu, Mélanie,Iannazzo, Laura
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- 5'-Deoxidation-5'-isopropyl-substituted-amino nucleoside compound and preparing method and application thereof
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The invention discloses a 5'-deoxidation-5'-isopropyl-substituted-amino nucleoside compound shown in a formula 7, a preparing method of the compound shown in the formula 7 and application of the compound shown in the formula 7 to preparing a 5'-deoxidation-5'-polysubstitution amino nucleoside compound 1 as a midbody. The formula is defined in the description.
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Paragraph 0325-0329
(2019/05/28)
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- S-Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C-Alkylation
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A tandem enzymatic strategy to enhance the scope of C-alkylation of small molecules via the in situ formation of S-adenosyl methionine (SAM) cofactor analogues is described. A solvent-exposed channel present in the SAM-forming enzyme SalL tolerates 5′-chloro-5′-deoxyadenosine (ClDA) analogues modified at the 2-position of the adenine nucleobase. Coupling SalL-catalyzed cofactor production with C-(m)ethyl transfer to coumarin substrates catalyzed by the methyltransferase (MTase) NovO forms C-(m)ethylated coumarins in superior yield and greater substrate scope relative to that obtained using cofactors lacking nucleobase modifications. Establishing the molecular determinants that influence C-alkylation provides the basis to develop a late-stage enzymatic platform for the preparation of high value small molecules.
- McKean, Iain J. W.,Sadler, Joanna C.,Cuetos, Anibal,Frese, Amina,Humphreys, Luke D.,Grogan, Gideon,Hoskisson, Paul A.,Burley, Glenn A.
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supporting information
p. 17583 - 17588
(2019/11/11)
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- Purine compound containing bicyclic group, and preparation method thereof
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The invention provides a purine compound containing a bicyclic group which is shown as a formula (I) and a formula (II) and a pharmaceutically acceptable salt, and a preparation method thereof. The compound is an inhibitor of histone methyltransferase DOT1L, and can be used for treating diseases caused by the abnormity of enzyme activity, such as tumor.
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Paragraph 0208; 0212
(2019/10/01)
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- Convenient preparation of pinometostat and related 5′-deoxy-5′-amino adenosine derivatives as well as their activity against DOT1L
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From adenosine and 2′-C-Me adenosine, a 3-step route towards nucleoside DOT1L inhibitors, including pinometostat, EPZ5677, and FED1, was established. With useful structural-activity relationship information, the newly prepared 2′-C-Me adenosine derivative
- Liu, Tongchao,Ren, Huanming,Li, Cong,Chen, Guohua,Cheng, Maosheng,Zhao, Dongmei,Shen, Jingkang,Li, Jia,Zhou, Yubo,Xiong, Bing,Chen, Yue-Lei
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p. 415 - 417
(2018/01/10)
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- SELECTIVE INHIBITORS OF PROTEIN ARGININE METHYLTRANSFERASE 5 (PRMT5)
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The disclosure is directed to compounds of Formula (I) and Formula (II). Methods of their use and preparation is other described.
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- COMPOSITIONS OF SELENOORGANIC COMPOUNDS AND METHODS OF USE THEREOF
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The present application relates to compositions comprising selenium compounds, such as 5'-Methylselenoadenosine, Se-Adenosyl-L-homocysteine, Gamma-glutamyl-methylseleno-cysteine, a compound of Formula (I), Formula (II), or Formula (III), and combinations thereof, and methods of using the same for modulating glucose metabolism in a subject.
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Paragraph 0252; 0254; 0255
(2017/04/04)
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- Se-Adenosyl-L-Selenohomocysteine Selenoxide As A Modulator Of Methyltransferase And Other Activities
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The invention relates to a compound of the structural formula or a hydrate or an isotope thereof. The invention also relates to a preparation method thereof and methods of providing dietary organoselenium, inactivating an enzyme, modulating the activity of a protein (e.g., methyltransferase) or nucleic acid, identifying a methyltransferase that reacts with compound, and oxidizing a methyltransferase-reactive substrate.
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Paragraph 0056
(2016/04/26)
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- Modification of the length and structure of the linker of N6-benzyladenosine modulates its selective antiviral activity against enterovirus 71
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Very recently, we demonstrated that N6-isopentenyladenosine, a cytokinin nucleoside, exerts a potent and selective antiviral effect on the replication of human enterovirus 71. The present study is devoted to the structure optimization of another natural compound: N6-benzyladenosine. We mainly focused on the exploration of the size and nature of the linker between the adenine and the phenyl ring, as well as on the necessity of the D-ribose residue. More than 30 analogues of N6-benzyladenosine were prepared and their antiviral properties were evaluated. Two main methodologies were used for preparation: N6-acetyl-2′,3′,5′-tri-O-acetyladenosine can be regioselectively alkylated either by alkyl halides under base promoted conditions or by alcohols in Mitsunobu reactions. After deacylation with 4 M PrNH2 in MeOH at room temperature for one day, the desired products were obtained in overall high yields. Analysis of the structure-activity relationship clearly shows that the optimal size of the linker is limited to 2 or 3 atoms (compounds 4-7). 2′-Deoxyadenosine derivatives did not elicit any inhibitory or cytotoxic effect, while 5′-deoxynucleosides still induced some cell protective antiviral activity. Based on these observations, it can be hypothesized that there may be another mechanism that is at the base of the antiviral activity of these compounds against enterovirus 71 besides a possible 5′-triphosphorylation followed by a putative inhibitory effect on RNA synthesis.
- Drenichev, Mikhail S.,Oslovsky, Vladimir E.,Sun, Liang,Tijsma, Aloys,Kurochkin, Nikolay N.,Tararov, Vitali I.,Chizhov, Alexander O.,Neyts, Johan,Pannecouque, Christophe,Leyssen, Pieter,Mikhailov, Sergey N.
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- COMPOSITIONS COMPRISING SELENIUM AND USE OF SAME FOR THE TREATMENT AND PREVENTION OF DISEASE OR CONDITIONS ASSOCIATED WITH MITOCHONDRIAL DYSFUNCTION
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The present application relates to compositions comprising selenium (e.g., selenium enriched yeast and selenium containing compounds obtained or derived therefrom) and methods of using the same to treat and inhibit obesity, diabetes and related conditions
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Page/Page column 125-126
(2014/09/29)
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- Structure-guided design of fluorescent S-adenosylmethionine analogs for a high-throughput screen to target SAM-I riboswitch RNAs
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Many classes of S-adenosylmethionine (SAM)-binding RNAs and proteins are of interest as potential drug targets in diverse therapeutic areas, from infectious diseases to cancer. In the former case, the SAM-I riboswitch is an attractive target because this structured RNA element is found only in bacterial mRNAs and regulates multiple genes in several human pathogens. Here, we describe the synthesis of stable and fluorescent analogs of SAM in which the fluorophore is introduced through a functionalizable linker to the ribose. A Cy5-labeled SAM analog was shown to bind several SAM-I riboswitches via in-line probing and fluorescence polarization assays, including one from Staphylococcus aureus that controls the expression of SAM synthetase in this organism. A fluorescent ligand displacement assay was developed and validated for high-throughput screening of compounds to target the SAM-I riboswitch class.
- Hickey, Scott F.,Hammond, Ming C.
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p. 345 - 356
(2014/04/03)
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- Supramolecular assemblies of nucleoside functionalized carbon nanotubes: Synthesis, film preparation, and properties
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Nucleoside-functionalized multi-walled carbon nanotubes (N-MWCNTs) were synthesized and characterized. A self-organization process using hydrogen bonding interactions was then used for the fabrication of self-assembled N-MWCNTs films free of stabilizing agents, polymers, or surfactants. Membranes were produced by using a simple water-dispersion-based vacuum-filtration method. Hydrogen-bond recognition was confirmed by analysis with IR spectroscopy and TEM images. Restoration of the electronic conduction properties in the N-MWCNTs membranes was performed by removing the organic portion by thermal treatment under an argon atmosphere to give d-N-MWCNTs. Electrical conductivity and thermal gravimetric analysis (TGA) measurements confirmed the efficiency of the annealing process. Finally, oxidative biodegradation of the films N-MWCNTs and d-N-MWCNTs was performed by using horseradish peroxidase (HRP) and low concentrations of H2O2. Our results confirm that functional groups play an important role in the biodegradation of CNT by HRP: N-MWCNTs films were completely biodegraded, whereas for d-N-MWCNTs films no degradation was observed, showing that the pristine CNT undergoes minimal enzyme-catalyzed oxidation This novel methodology offers a straightforward supramolecular strategy for the construction of conductive and biodegradable carbon nanotube films. Conductive and biodegradable films: A self-organization process using hydrogen-bond interactions (see scheme, MWCNT=multiwalled carbon nanotube) is used for the fabrication of conductive and biodegradable carbon nanotube films totally free of stabilizing agents, polymers, or surfactants.
- Micoli, Alessandra,Turco, Antonio,Araujo-Palomo, Elsie,Encinas, Armando,Quintana, Mildred,Prato, Maurizio
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supporting information
p. 5397 - 5402
(2014/05/20)
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- Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L
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Histone3-lysine79 (H3K79) methyltransferase DOT1L has been found to be a drug target for acute leukemia with MLL (mixed lineage leukemia) gene translocations. A total of 55 adenosine-containing compounds were designed and synthesized, among which several potent DOT1L inhibitors were identified with Ki values as low as 0.5 nM. These compounds also show high selectivity (>4500-fold) over three other histone methyltransferases. Structure-activity relationships (SAR) of these compounds for their inhibitory activities against DOT1L are discussed. Potent DOT1L inhibitors exhibit selective activity against the proliferation of MLL-translocated leukemia cell lines MV4;11 and THP1 with EC50 values of 4-11 μM. Isothermal titration calorimetry studies showed that two representative inhibitors bind with a high affinity to the DOT1L:nucleosome complex and only compete with the enzyme cofactor SAM (S-adenosyl-l-methionine) but not the substrate nucleosome.
- Anglin, Justin L.,Deng, Lisheng,Yao, Yuan,Cai, Guobin,Liu, Zhen,Jiang, Hong,Cheng, Gang,Chen, Pinhong,Song, Yongcheng,Dong, Shuo
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supporting information
p. 8066 - 8074,9
(2020/09/15)
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- MODULATORS OF HISTONE METHYLTRANSFERASE, AND METHODS OF USE THEREOF
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Disclosed are compounds, pharmaceutical compositions containing the compounds, and the uses of the compounds and compositions as modulators of histone methyltransferases, and for treating diseases influenced by modulation of histone methyltransferase activity.
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Page/Page column 179-180
(2012/06/30)
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- A Selenium-Based Click AdoMet Analogue for Versatile Substrate Labeling with Wild-Type Protein Methyltransferases
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Protein methylation is catalyzed by S-adenosyl-L-methionine-dependent protein methyltransferases (MTases), and this posttranslational modification serves diverse cellular functions. Some MTases seem to exhibit broad substrate specificities and comprehensive methods for target profiling are needed. Here we report the synthesis of a new AdoMet analogue for enzymatic transfer of a small propargyl group and labeling of modified proteins through copper-catalyzed azide-alkyne cycloaddition (CuAAC). Replacement of sulfur by selenium strongly enhanced the stability of the progargylic cofactor, leading, in combination with better activation by the selenonium center, to higher enzymatic reactivity. A broad spectrum of wild-type protein MTases acting on lysine, arginine, and glutamine residues accept this cofactor and modified substrates can be efficiently labeled by CuAAC click chemistry.
- Willnow, Sophie,Martin, Michael,Luescher, Bernhard,Weinhold, Elmar
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experimental part
p. 1167 - 1173
(2012/08/13)
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- Structure-guided design of a methyl donor cofactor that controls a viral histone H3 lysine 27 methyltransferase activity
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vSET (a viral SET domain protein) is an attractive polycomb repressive complex 2 (PRC2) surrogate to study the effect of histone H3 lysine 27 (H3K27) methylation on gene transcription, as both catalyze histone H3K27 trimethylation. To control the enzymatic activity of vSET in vivo with an engineered S-adenosyl-l-methionine (SAM) analogue as methyl donor cofactor, we have carried out structure-guided design, synthesis, and characterization of orthogonal vSET methyltransferase mutant/SAM analogue pairs using a "bump-and-hole" strategy.
- Li, Jiaojie,Wei, Hua,Zhou, Ming-Ming
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supporting information; experimental part
p. 7734 - 7738
(2012/01/13)
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- A broad spectrum anticancer nucleoside with selective toxicity against human colon cells in vitro
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2′,3′-Bis-O-tert-butyldimethylsilyl-5′-deoxy-5′-[N- (methylcarbamoyl)amino]-N6-(N-phenylcarbamoyl)adenosine, a new member of the N6,5′-bis-ureidoadenosine class of anticancer nucleosides, is found to exhibit broad spectrum antiproliferative activity. A majority of the cell lines in the NCI-60 are inhibited with an average GI 50 = 3.13 μM. Selective toxicity against human colon cancer cell lines (COLO 205, HCC-2998, HCT-116, HT29, KM12) was also exhibited (LC 50's = 6-10 μM).
- Shelton, Jadd R.,Burt, Scott R.,Peterson, Matt A.
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scheme or table
p. 1484 - 1487
(2011/04/23)
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- Synthesis and antimicrobial activity of some novel nucleoside analogues of adenosine and 1,3-dideazaadenosine
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A number of nucleoside analogues have been synthesized and evaluated for their antibacterial and antifungal activities against Staphylococcus aureus, Group D Streptococcus, Pseudomonas aeruginosa, Proteus spp., Salmonella spp., Aspergillus fumigatus, Penicillium marneffei, Candida albicans, Cryptococcus neoformans, and Mucor spp. The compounds 1, 4, and 6 emerged as potent antibacterial agents with MIC values of 0.75, 0.38, and 0.19 μM, respectively, against group D Streptococcus. Further, the results suggest that the molecules 4, 6, and 7 would be potent antifungal agents as they show substantial degree of inhibition toward the growth of pathogenic fungi with MICs of 0.75, 0.38, and 0.38 μM, respectively.
- Srivastava, Richa,Bhargava, Anudita,Singh, Ramendra K.
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p. 6239 - 6244
(2008/03/18)
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- Adenylate Deaminase (5′-Adenylic Acid Deaminase, AMPDA)-Catalyzed Deamination of 5′-Deoxy-5′-Substituted and 5′-Protected Adenosines: A Comparison with the Catalytic Activity of Adenosine Deaminase (ADA)
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The enzyme adenylate deaminase (AMPDA) is able to catalyze the hydrolytic deamination of 5′-substituted and 5′-protected 5′ -deoxyadenosines, whereas limited or no activity is shown by adenosine deaminase (ADA) towards the same substrates. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Ciuffreda, Pierangela,Loseto, Angela,Alessandrini, Laura,Terraneo, Giancarlo,Santaniello, Enzo
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p. 4748 - 4751
(2007/10/03)
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- A CONVENIENT METHOD FOR THE SYNTHESIS AND RANEY NICKEL DESULFURIZATION OF 5'-DEOXY-5'-METHYLTHIOADENOSINE
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A convenient procedure for the preparation of 5'-deoxy-5'-methylthioadenosine is reported.Chlorination of adenosine with thionyl chloride yielded 5'-chloro-5'-deoxyadenosine.Reaction of 5'-chloro-5'deoxyadenosine with aqueous methylmercaptide anion yielded 5'-deoxy-5'-methylthioadenosine.Hydrogenolysis of 5'-deoxy-5'-methylthioadenosine over Raney nickel in water produced 5'-deoxyadenosine.This procedure affords a high yield of readily purified 5'-deoxyadenosine while avoiding the use of anhydrous solvents and pyrophoric reagents.The procedure illustrates the utility of sulfur reagents to accomplish high value added transformations in nucleoside chemistry.Key words: 5'-Deoxyadenosine; 5'-deoxy-5'methylthioadenosine; 5'-chloro-5'-deoxyadenosine; Raney nickel desulfurization.
- Scovill, John P.,Thigpen, Don L.,Lemley, Paul V.
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p. 149 - 152
(2007/10/02)
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- Arsenic Compounds from the Kidney of the Giant Clam Tridacna maxima: Isolation and Identification of an Arsenic-containing Nucleoside
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The kidney of the giant clam Tridacna maxima contains algal arsenic compounds, probably as a consequence of the clam's symbiotic relationship with unicellular algae (zooxanthallae).Extraction of Tridacna kidneys yielded three novel arsenic compounds, N-(5'-deoxy-5'-dimethylarsinoyl-β-D-ribosyloxycarbonyl)glycine 5, (2S)-3-(5'-deoxy-5'-dimethylarsinoyl-β-D-ribosyloxy)-2-hydroxypropanoic acid 4a, and (2R)-3-(5'-deoxy-5'-dimethylarsinoyl-β-D-ribosyloxy)-2-hydroxypropanoic acid 4b, in addition to four previously reported dimethylarsinoylribosides.The structures of the three new compounds were assigned chiefly from NMR data, and those for compounds 4a and 4b were confirmed by synthesis.Extraction of a second batch of Tridacna kidneys gave, in addition to compounds identified in the first extraction, (2S)-3-sulfate 18 and two novel compounds: an arsenic-containing nucleoside, 9-(5'-deoxy-5'-dimethylarsinoyl)-9H-adenosine 16 and N-taurine 21.Syntheses of compounds 16 and 21 are reported.The presence of the nucleoside 16 in Tridacna, as a consequence of algal metabolism, supports a proposed pathway for the biogenesis of arsenic-containig ribosides by algae involving methylation and adenosylation by S-adenosylmethionine.A biogenetic pathway for compound 21 involving donation of the 3-amino-3-carboxypropyl moiety of S-adenosylmethionine is also proposed.The presence of both compounds 16 and 21 in Tridacna may represent the first example of donation, by S-adenosylmethionine, of all three of its groups to a single acceptor (arsenic) within one organism.
- Francesconi, Kevin A.,Edmonds, John S.,Stick, Robert V.
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p. 1349 - 1358
(2007/10/02)
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- 9-(4-METHOXYPHENYL)XANTHEN-9-THIOL: A USEFUL REAGENT FOR THE PREPARATION OF THIOLS
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Treatment of 5'-chloro-5'-deoxynucleosides (5) with the conjugate base of 9-(4-methoxyphenyl)xanthen-9-thiol (3b), followed by acid-promoted removal of the 5'-S- group in the presence of pyrrole gives the corresponding 5'-deoxy-5'-mercaptonucleosides (7) in good yields.
- Marriott, Jonathan H.,Mottahedeh, Mina,Reese, Colin B.
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p. 7485 - 7488
(2007/10/02)
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- Methylthioribose analogs, their preparation and use as medicinal agents and biocides
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Compounds of the formula: STR1 wherein R is H, Cl, F, Br, I or R1 S--, in which R1 is C1 -C10 linear or branched chain alkyl or halogenated linear or branched chain alkyl, and wherein R2, R3 and R4 are the same or different and each is H-- or --OH, with the proviso that at least one of R2, R3 and R4 is hydroxy and the further proviso that when R2, R3 and R4 are all OH, R1 is other than methyl, are useful in inhibiting the growth of MTR kinase-dependent microorganisms and parasitic protazoans. The compounds wherein R is R1 S are novel, except those wherein R1 is methyl or isobutyl when R2, R3 and R4 are all OH.
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- AN IMPROVED SYNTHESIS OF S-ADENOSYL-L-HOMOCYSTEINE AND RELATED COMPOUNDS
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5'-Chloro-5'-deoxy-2',3'-O-isopropylideneadenosine reacts with disodium salts of L-homocysteine, L-cysteine or 3-mercaptopropanoic acid in liquid ammonia to afford 2',3'-O-isopropylidene derivatives which are easily desalted by chromatography on octadecyl-silica column.On acid treatment, the high purity preparations of S-adenosyl-L-homocysteine, S-adenosyl-L-cysteine, and 5'-carboxyethylthio-5'-deoxyadenosine are obtained in respectable yield.
- Holy, Antonin,Rosenberg, Ivan
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p. 1514 - 1518
(2007/10/02)
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- Process for preparing adenosine derivatives of anti-inflammatory and analgesic activity
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Therapeutic composition of antiinflammatory, analgesic and antipyretic activity comprising as its active principle at least one component of general formula: STR1 in which: R is a linear or branched alkyl radical of 1-18 C atoms, or phenylalkylene in which the alkylene chain has 1-6 C atoms R1 is H, an aliphatic acyl radical of 1-6 C atoms or an aromatic acyl radical R2 is H, an aliphatic acyl radical of 1-6 C atoms, or an aromatic acyl radical, or alternatively the radicals R2 together form an isopropylidene chain n is 0 or 1.
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- The Base-sugar Conformation of Certain Derivatives of Adenosine
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Base-sugar conformations of a range of adenosine derivatives have been confirmed by n.m.r. and c.d. measurements.The implications of the conformations for certain chemical properties, such as the formation of 5',8-cycloderivatives, are discussed.
- Gani, David,Johnson, Alan W.
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p. 1197 - 1204
(2007/10/02)
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- REACTION OF NUCLEOSIDES WITH THIONYL CHLORIDE; PREPARATION OF THE DEOXY DERIVATIVES OF CYTIDINE AND ADENOSINE
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On reaction of thionyl chloride with cytidine and adenosine in refluxing acetonitrile, the 5'-chloro-2',3'-sulphinyl derivatives I and VII are formed in a quantitative yield.On heating in dimethylformamide, compound I affords 5'-chloro-5'-deoxycyclocytidine (II) which is hydrolyzed in alkali to the arabinosyl derivative III; reduction of III with tributyltin hydride gives the 5'-deoxyarabinosyl derivative IV.The sulphinyl derivative I is hydrolyzed to 5'-chloro-5'-deoxycytidine (V) which is reduced to 5'-deoxycytidine (VI).Analogously, the sulphinyl derivative VII affords 5'-chloro-5'-deoxyadenosine (VIII) and the reduction of VIII gives 5'-deoxyadenosine (IX).Of these compounds, the 5'-chloro-5'-deoxyarabinosyl derivative as the only one shows an inhibitory effect towards the L1210 cell growth.
- Hrebabecky, Hubert,Brokes, Josef,Beranek, Jiri
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p. 599 - 605
(2007/10/02)
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