- The supramolecular helical architecture of 8-oxoinosine and 8-oxoguanosine derivatives
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The 8-oxoguanosine derivative 1 and the 8-oxoinosine derivative 2b, with appropriate substituents on their ribose moieties, form hexagonal lyotropic mesophases in hydrocarbon solvents. Small-angle X-ray scattering analysis of a film of 1 and of the mesophase of 2b, and NMR and CD spectra of isotropic solutions of 2b, indicate that in both cases the supramolecular structures adopted are continuous helices formed by a hydrogen-bond network between the heterocyclic bases. Notably, while derivative 2b, which bears large substituents on its ribose moiety, undergoes self-assembly and mesophase formation, oxoinosine 2a, with only decanoyl groups on its ribose moiety, does not. This may be ascribed to the reduced amphiphilic properties of the latter and the absence of aromatic groups.
- Lena, Stefano,Cremonini, Mauro A.,Federiconi, Francesco,Gottarelli, Giovanni,Graziano, Carla,Laghi, Luca,Mariani, Paolo,Masiero, Stefano,Pieraccini, Silvia,Spada, Gian Piero
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- Salvadenosine, a 5β-deoxy-5β-(methylthio) nucleoside from the Bahamian tunicate Didemnum sp.
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Salvadenosine, (1) a rare 5β-deoxy-5β-(methylthio) nucleoside, was isolated from the deep-water Bahaman tunicate Didemnum sp. The structure was solved by integrated analysis of MS and 1D and 2D NMR data. We revise the structure of the known natural product, hamiguanosinol, which is a constitutional isomer of 1, to 5 by interpretation of the spectroscopic data and comparison with synthesized nucleosides.
- Jamison, Matthew T.,Boddy, Christopher N.,Molinski, Tadeusz F.
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- Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD+ analogues
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ADP-ribosyl transferases with diphtheria toxin homology (ARTDs) catalyse the covalent addition of ADP-ribose onto different acceptors forming mono- or poly(ADP-ribos)ylated proteins. Out of the 18 members identified, only four are known to synthesise the complex poly(ADP-ribose) biopolymer. The investigation of this posttranslational modification is important due to its involvement in cancer and other diseases. Lately, metabolic labelling approaches comprising different reporter-modified NAD+ building blocks have stimulated and enriched proteomic studies and imaging applications of ADP-ribosylation processes. Herein, we compare the substrate scope and applicability of different NAD+ analogues for the investigation of the polymer-synthesising enzymes ARTD1, ARTD2, ARTD5 and ARTD6. By varying the site and size of the NAD+ modification, suitable probes were identified for each enzyme. This report provides guidelines for choosing analogues for studying poly(ADP-ribose)-synthesising enzymes.
- Wallrodt, Sarah,Simpson, Edward L.,Marx, Andreas
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- Changing nucleotide specificity of the DEAD-box helicase Hera abrogates communication between the Q-motif and the P-loop
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DEAD-box proteins disrupt or remodel RNA and protein/ RNA complexes at the expense of ATP. The catalytic core is composed of two flexibly connected RecA-like domains.The N-terminal domain contains most of the motifs involved in nucleotide binding and serves as a minimalistic model for helicase/nucleotide interactions. A single conserved glutamine in the so-called Q-motif has been suggested as a conformational sensor for the nucleotide state. To reprogram the Thermus thermophilus RNA helicase Hera for use of oxo- ATP instead of ATP and to investigate the sensor function of the Q-motif, we analyzed helicase activity of Hera Q28E. Crystal structures of the Hera N-terminal domain Q28E mutant (TthDEAD-Q28E) in apo- and ligand-bound forms show that Q28E does change specificity from adenine to 8- oxoadenine. However, significant structural changes accompany the Q28E mutation, which prevent the P-loop from adopting its catalytically active conformation and explain the lack of helicase activity of Hera-Q28E with either ATP or 8-oxo-ATP as energy sources. 8-Oxo-adenosine, 8-oxo-AMP, and 8-oxo-ADP weakly bind to TthDEAD-Q28E but in noncanonical modes. These results indicate that the Q-motif not only senses the nucleotide state of the helicase but could also stabilize a catalytically competent conformation of the Ploop and other helicase signature motifs. Copyright by Walter de Gruyter.
- Strohmeier, Julian,Hertel, Ines,Diederichsen, Ulf,Rudolph, Markus G.,Klostermeier, Dagmar
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- Coumarin-purine ribofuranoside conjugates as new agents against hepatitis c virus
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About 3% of world's population is infected by the hepatitis C virus (HCV), for which prophylactic vaccine is not available yet. Nowadays, pegylated interferon-α and ribavirin are commonly used to treat HCV; unfortunately these drugs often produce significant side effects. Upon the desperate need of anti-HCV drugs, a plan to establish a new compound library was set that included leads with high antiviral activity, good hydrophilicity, yet low toxicity. Accordingly, 26 new conjugated compounds were synthesized through the chemical coupling of various 9-(β-d-ribofuranosyl)purine-8-thiones with 3-(chloromethyl)coumarins bearing various substituents. A SCH2 unit was used to link the coumarin and the purine moieties. The three hydroxyl groups at the 2′-, 3′-, and 5′-positions were selectively protected with an acyl or acetal group in these coumarin-purine ribofuranosides. Their anti-HCV and cytostatic determination assays were performed, and the structure-activity relationship was established. Three conjugates in the family of 8-(coumarin-3′-yl)methylthio-9-(β-d-ribofuranos-1′-yl)purine possessed an appealing ability to inhibit HCV replication with EC50 between 5.5 and 6.6 μM and EC90 of 20 μM. These data in the new compound library provide clues for the future in the development of anti-HCV leads for viral eradication.
- Hwu, Jih Ru,Lin, Shu-Yu,Tsay, Shwu-Chen,De Clercq, Erik,Leyssen, Pieter,Neyts, Johan
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Read Online
- An Irreversible Inhibitor of HSP72 that Unexpectedly Targets Lysine-56
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The stress-inducible molecular chaperone, HSP72, is an important therapeutic target in oncology, but inhibiting this protein with small molecules has proven particularly challenging. Validating HSP72 inhibitors in cells is difficult owing to competition with the high affinity and abundance of its endogenous nucleotide substrates. We hypothesized this could be overcome using a cysteine-targeted irreversible inhibitor. Using rational design, we adapted a validated 8-N-benzyladenosine ligand for covalent bond formation and confirmed targeted irreversible inhibition. However, no cysteine in the protein was modified; instead, we demonstrate that lysine-56 is the key nucleophilic residue. Targeting this lysine could lead to a new design paradigm for HSP72 chemical probes and drugs.
- Pettinger, Jonathan,Le Bihan, Yann-Va?,Widya, Marcella,van Montfort, Rob L. M.,Jones, Keith,Cheeseman, Matthew D.
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- Cyclic dinucleotide analogues, pharmaceutical composition of analogues and applications of analogues and pharmaceutical composition
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The invention discloses cyclic dinucleotide analogues, a pharmaceutical composition of the analogues and applications of the analogues and the pharmaceutical composition. The cyclic dinucleotide analogs (I), an isomer, prodrug, stable isotope derivative or pharmaceutically acceptable salt of the analogs have a structure shown in the specification. The cyclic dinucleotide analogs provided by the invention can be used as regulators of stimulator of interferon genes (STIG) and related signaling pathways, and can effectively treat and/or alleviate multiple types of diseases, including but not limited to malignant tumors, inflammation, autoimmune diseases and infectious diseases; and in addition, the STING regulators can also be used as vaccine adjuvants.
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Paragraph 0380; 0381; 0382; 0383
(2020/04/17)
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- Production process of arabinoside
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The invention discloses a production process of arabinoside, relates to the technical field of arabinoside synthesis, and solves the technical problems that in the existing production process of arabinoside, after-treatment of an acetic acid buffer agent reaction solution is difficult, a 1, 2-dichloroethane solvent is difficult to recover, potassium permanganate is slow to charge, and the reactiontime is too long. The production process of arabinoside comprises the following steps: synthesis of 8-bromoadenosine, synthesis of 8-bromo-2'-O-p-toluenesulfonyl adenosine, synthesis of 8-hydroxy-4'-acetoxy-5'-acetoxymethyl-3'-p-toluenesulfonyl adenosine and synthesis of arabinoside. In the production process of arabinoside, after-treatment of wastewater is convenient, hazardous waste is convenient to treat, the process cost is low, and the reaction time is short.
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Paragraph 0026; 0028; 0033; 0035; 0040; 0042
(2020/12/31)
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- Synthetic method for 8-bromoadenosine
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The invention discloses a synthetic method for 8-bromoadenosine, belonging to the field of chemical synthesis. The product namely 8-bromoadenosine is obtained with adenosine as a raw material through8-bromo substitution. According to the invention, the usage amount of a substrate Br2 and the concentration and pH range of an acetic acid-sodium acetate buffer solution are controlled, and the usageamount of a quenching agent NaHSO3 is reduced at the same time, so process cost is comprehensively reduced, and the index of COD in wastewater is decreased; and directed at the problem of returning ofa product to a raw material due to a quenching reaction of NaHSO3, quenching time is shortened, so the yield of the product is improved.
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Paragraph 0017-0028
(2018/07/06)
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- Selective C8-Metalation of Purine Nucleosides via Oxidative Addition
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8-Bromo-2′-deoxy-3′,5′-di-O-acetylguanosine (1), 8-bromo-2′,3′,5′-tri-O-acetylguanosine (2), 8-bromo-2′-deoxy-3′,5′-di-O-acetyladenosine (3), and 8-bromo-2′,3′,5′-tri-O-acetyladenosine (4) react with [Pd(PPh3)4] via a C8-Br oxidative addition to give the C8-palladated azolato complexes [5]-[8] featuring an unprotonated N7 ring nitrogen atom. The complexes feature diastereotopic trans-disposed triphenylphosphine ligands, which allowed the determination of 2JPP for complexes of the type trans-[PdL2(PPh3)2] (2JPP = 442 Hz for [7]). In addition, two complex molecules of [7] form a trans-Watson-Crick/Hoogsteen AA base pair in the solid state. N7-protonation of the guanosine-derived complexes [5] and [6] with HBF4·Et2O and of adenosine-derived complexes [7] and [8] using lutidinium triflate yields complexes [9]BF4 and [10]BF4 and complexes [11]OTf and [12]OTf bearing protic NH,NR-NHC ligands derived from guanosine and adenosine, respectively.
- Kampert, Florian,Brackemeyer, Dirk,Tan, Tristan Tsai Yuan,Ekkehardt Hahn
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p. 4181 - 4185
(2018/11/23)
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- 6,8-DISUBSTITUTED PURINE COMPOSITIONS
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6,8-Disubstituted purines which can be used in drug and cosmetic compositions and/or applications are provided. These 6,8-disubstituted purines have a wide range of biological activities, including for example anti-inflammatory, anti-senescent, as well as well as other activities which are especially useful in pharmaceutical and cosmetic applications. The 6,8-disubstituted purine compounds and compositions containing such 6,8-disubstituted purines provide growth-regulatory, differentiating, antisenescent and antiaging properties with improved selectivities and efficiencies and lower toxicities than analogues known heretofore.
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Paragraph 0128
(2013/03/28)
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- An efficient and facile methodology for bromination of pyrimidine and purine nucleosides with sodium monobromoisocyanurate (SMBI)
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An efficient and facile strategy has been developed for bromination of nucleosides using sodium monobromoisocyanurate (SMBI). Our methodology demonstrates bromination at the C-5 position of pyrimidine nucleosides and the C-8 position of purine nucleosides. Unprotected and also several protected nucleosides were brominated in moderate to high yields following this procedure.
- Maity, Jyotirmoy,Stromberg, Roger
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p. 12740 - 12750
(2013/11/06)
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- Oxidation of adenosine and inosine: The chemistry of 8-Oxo-7,8- dihydropurines, purine iminoquinones, and purine quinones as observed by ultrafast spectroscopy
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Oxidative damage to purine nucleic acid bases proceeds through quinoidal intermediates derived from their corresponding 8-oxo-7,8-dihydropurine bases. Oxidation studies of 8-oxo-7,8-dihyroadenosine and 8-oxo-7,8-dihydroinosine indicate that these quinoidal species can produce stable cross-links with a wide variety of nucleophiles in the 2-positions of the purines. An azide precursor for the adenosine iminoquinone has been synthesized and applied in ultrafast transient absorption spectroscopic studies. Thus, the adenosine iminoquinone can be observed directly, and its susceptibility to nucleophilic attack with various nucleophiles as well as the stability of the resulting cross-linked species have been evaluated. Finally, these observations indicate that this azide might be a very useful photoaffinity labeling agent, because the reactive intermediate, adenosine iminoquinone, is such a good mimic for the universal purine base adenosine.
- Nilov, Denis I.,Komarov, Dmitry Y.,Panov, Maxim S.,Karabaeva, Kanykey E.,Mereshchenko, Andrey S.,Tarnovsky, Alexander N.,Wilson, R. Marshall
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supporting information
p. 3423 - 3438
(2013/05/08)
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- Synthesis and fluorescence properties of a full set of extended RNA base analogues
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The synthesis and photophysical characterization of a complete set of fluorescent RNA base analogues derived by conjugating benzofuran moiety at the 5- and 8-positions of pyrimidine and purine bases, respectively, are described. Benzofuran-modified pyrimidine and purine ribonucleoside analogues exhibit contrasting fluorescence properties. Pyrimidine analogues are moderately emissive with emission maximum in the visible region, and importantly, are highly sensitive to solvent polarity and viscosity changes. On the other hand, purine analogues are highly emissive and are minimally affected by solvation and viscosity effects. Thorough photophysical analysis reveals that the pyrimidine and purine ribonucleosides displaying distinct and probe-like fluorescence properties could be useful in designing nucleic acid based biophysical tools to study nucleic acid structure and function.
- Sabale, Pramod M,Nuthanakanti, Ashok,Srivatsan, Seergazhi G
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p. 1004 - 1013
(2013/09/12)
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- Promiscuous 8-alkoxyadenosines in the guide strand of an SiRNA: Modulation of silencing efficacy and off-pathway protein binding
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8-Alkoxyadenosines have the potential to exist in anti or syn conformations around the glycosidic bond when paired opposite to U or G in the complementary strands, thereby placing the sterically demanding 8-alkoxy groups in the major or minor groove, respectively, of duplex RNA. These modified bases were used as "base switches" in the guide strands of an siRNA to prevent off-pathway protein binding during delivery via placement of the alkoxy group in the minor groove, while maintaining significant RNAi efficacy by orienting the alkoxy group in the major groove. 8-Alkoxyadenosine phosphoramidites were synthesized and incorporated into the guide strand of caspase 2 siRNA at four different positions: two in the seed region, one at the cleavage junction, and another nearer to the 3'-end of the guide strand. Thermal stabilities of the corresponding siRNA duplexes showed that U is preferred over G as the base-pairing partner in the complementary strand. When compared to the unmodified positive control siRNAs, singly modified siRNAs knocked down the target mRNA efficiently and with little or no loss of efficacy. Doubly modified siRNAs were found to be less effective and lose their efficacy at low nanomolar concentrations. SiRNAs singly modified at positions 6 and 10 of the guide strand were found to be effective in blocking binding to the RNA-dependent protein kinase PKR, a cytoplasmic dsRNA-binding protein implicated in sequence-independent off-target effects.
- Ghanty, Uday,Fostvedt, Erik,Valenzuela, Rachel,Beal, Peter A.,Burrows, Cynthia J.
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supporting information
p. 17643 - 17652
(2013/01/15)
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- Synthesis and in vitro stability of nucleoside 5′-phosphonate derivatives
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Nucleoside derivatives are largely synthesized and tested to investigate their influence on platelet aggregation. It's well known that P2Y receptors play an important role in the regulation of platelet function and, as consequence, in controlling atherothrombotic events. The research of compounds that antagonize P2Y1 and, in particular, P2Y12 receptors is of great interest in the aim to obtain platelet aggregation inhibitors that are effective in the prevention and treatment of arterial thrombosis. In this study we present the synthesis and in vitro metabolic stability in human blood and rat liver homogenate of a new class of nucleoside derivatives, in particular 5′-phosphonate adenosine, inosine, guanosine and thioadenosine analogues also modified at the ribose moiety. On the basis of the results obtained we can hypothesize compounds 4 and 18 to have in vivo a relatively high stability.
- Vertuani, Silvia,Baldisserotto, Anna,Varani, Katia,Borea, Pier Andrea,De Marcos Maria Cruz, Bonache,Ferraro, Luca,Manfredini, Stefano,Dalpiaz, Alessandro
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supporting information; experimental part
p. 202 - 209
(2012/09/07)
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- Bromination at C-5 of pyrimidine and C-8 of purine nucleosides with 1,3-dibromo-5,5-dimethylhydantoin
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Treatment of the protected and unprotected nucleosides with 1,3-dibromo-5,5-dimethylhydantoin in aprotic solvents such as CH 2Cl2, CH3CN, or DMF effected smooth bromination of uridine and cytidine derivatives at C-5 of pyrimidine rings as well as adenosine and guanosine derivatives at C-8 of purine rings. Addition of Lewis acids such as trimethylsilyl trifluoromethanesulfonate enhanced the efficiency of bromination.
- Rayala, Ramanjaneyulu,Wnuk, Stanislaw F.
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experimental part
p. 3333 - 3336
(2012/07/30)
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- METHODS AND COMPOSITIONS RELATED TO MODIFIED ADENOSINES FOR CONTROLLING OFF-TARGET EFFECTS IN RNA INTERFERENCE
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Disclosed are compositions and methods related to modified nucleobases. Also disclosed are compositions and methods related to modified interfering RNAs. Also disclosed are compositions and methods related to modified adenonsine for controlling off-target effects in RNA interference.
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Page/Page column 50-51
(2011/10/13)
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- Two-step synthesis of novel, bioactive derivatives of the ubiquitous cofactor nicotinamide adenine dinucleotide (NAD)
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We report the design and concise synthesis, in two steps from commercially available material, of novel, bioactive derivatives of the enzyme cofactor nicotinamide adenine dinucleotide (NAD). The new synthetic dinucleotides act as sirtuin (SIRT) inhibitors and show isoform selectivity for SIRT2 over SIRT1. An NMR-based conformational analysis suggests that the conformational preferences of individual analogues may contribute to their isoform selectivity.
- Pesnot, Thomas,Kempter, Julia,Schemies, J?rg,Pergolizzi, Giulia,Uciechowska, Urszula,Rumpf, Tobias,Sippl, Wolfgang,Jung, Manfred,Wagner, Gerd K.
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supporting information; experimental part
p. 3492 - 3499
(2011/07/30)
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- X-ray crystal structures of halogen containing nucleobase derivatives in unsolvated and DMSO solvated forms
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A series of halogenated nucleobase derivatives 1-4 is reported to yield solvent-free (2) and DMSO solvated crystals (1, 3, 4) on the crystallization from DMSO with one of them (4) containing an additional molecule of water. The molecular and crystal structures are described and comparatively discussed with reference to previous results on related compounds. The molecule of 1 is planar, molecules of 2 and 3 show syn alignment with reference to the heterocyclic ring and common C2′-endo conformation of the ribose residue, while 4 is also syn aligned but C4′-exo in the sugar conformation. The packing structures reveal typical aggregations created via networks of hydrogen bonds. These involve conventional N-H···N, N-H···O and O-H···O interactions between nucleobase and ribose units as well as solvent molecules, additionally supported by weak C-H···O contacts but excluding the participation of halogen···halogen interactions as well as halogen···heteroatom contacts in the supramolecular structure formation. Springer Science+Business Media, LLC 2009.
- Eissmann, Frank,Schindler, Diana,Weber, Edwin
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experimental part
p. 245 - 254
(2011/01/03)
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- Bicyclic Compounds and Their Use
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The present invention provides fluorescent bicyclic compounds of the formula (I); wherein ring A, the broken lines -----, C1----C2, R4 and R1 are as defined herein. The invention also relates to nucleoside and nucleotide analogues of said compounds, and their use as biological markers.
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Page/Page column 22
(2009/12/23)
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- Synthesis and photophysical characterisation of fluorescent 8-(1 H-1,2,3-triazol-4-yl)adenosine derivatives
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A series of 8-(1-H-1,2,3-triazol-4-yl)-substituted adenosine derivatives have been symthesised by using Sonogashira cross-coupling and click chemistry. The use of click chemistry enables an easy access to different substituents in the 4- posilion of the triazole ring. The modified nucleosides show high absorptivities due to a single strongly allowed electronic transition and, for some of the derivatives, high quantum yields in organic as well as in water solution making them promising as fluorescent probes in nucleic acid contexts. Furthermore, the different substituents of the 1,2,3-triazole makes the wavelength of emission tunable without changing the absorption properties substantially. Wiley-VCH Verlag GmbH & Co. KGaA.
- Dyrager, Christine,Boerjesson, Karl,Diner, Peter,Elf, Annelie,Albinsson, Bo,Wilhelmsson, L. Marcus,Grotli, Morten
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scheme or table
p. 1515 - 1521
(2009/07/11)
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- The elusive 8-fluoroadenosine: a simple non-enzymatic synthesis and characterization
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The only successful synthesis of 8-fluoroadenosine reported until now relied on an enzymatic removal of the acetate protecting groups using thermally resistant hydrolases. In the present communication we describe the first non-enzymatic synthesis of 8-fluoroadenosine. According to this, the C8-fluorine atom was introduced in a halogen-exchange process performed at elevated temperature. The chief obstacle in the synthesis of 8-fluoroadenosine, the removal of the protecting groups in the presence of the labile C8-F bond, was addressed by judicious choice of acid-labile protecting groups. Their deprotection in the presence of C8-F is described. Using this newly developed procedure, significant quantities of 8-fluoroadenosine were synthesized and, for the first time, its physicochemical properties including pH-dependent stability, examined in detail. The intermediate generation of 8-fluoroadenosines as a tool to increase the reaction rates of nucleophilic substitutions was briefly examined and successfully demonstrated with the example of 8-cyanoadenosine. The presented procedure is applicable to the synthesis of various adenosine analogs with potential pharmacological significance.
- Butora, Gabor,Schmitt, Christoph,Levorse, Dorothy A.,Streckfuss, Eric,Doss, George A.,MacCoss, Malcolm
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p. 3782 - 3789
(2008/02/01)
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- Synthesis of 8-aminoadenosine 5′-(aminoalkyl phosphates), analogues of aminoacyl adenylates
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A short and efficient route for the synthesis of aminoalkyl 8-aminoadenylates, potential aminoacyl-tRNA synthetase inhibitors, is presented. Aminoalkyl 8-aminoadenylates were synthesized using a 5′-H-phosphonate strategy involving minimal protecting group manipulations and a single final deprotection step.
- Yousefi-Salakdeh, Esmail,Murtola, Merita,Zetterberg, Anders,Yeheskiely, Esther,Stroemberg, Roger
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p. 2653 - 2659
(2007/10/03)
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- N3,5′-Cycloxanthosine, the first natural occurrence of a cyclonucleoside
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An Eryus sp. of marine sponge from the Great Australian Bight has yielded the first reported natural occurrence of a cyclonucleoside, N 3,5'-cycloxanthosine. The structure of N3,5'- cycloxanthosine was confirmed by detailed spectroscopic analysis and total synthesis. 2005 American Chemical Society and American Society of Pharmacognosy.
- Capon, Robert J.,Trotter, Nicholas S.
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p. 1689 - 1691
(2008/09/17)
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- Synthesis of novel 2-aryl AICAR derivatives
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Novel 2-aryl AICAR (5-Amino-1-β-D-ribofuranosylimidazole-4- carboxamide) derivatives 8 were synthesized via the Suzuki-Miyaura cross-coupling reactions of 8-bromoadenosine. Following conversion of the adenine moiety of 4 to hypoxanthine (5) and the introduction of a MEM group, hydrolysis of 7 gave desired 2-aryl AICAR derivatives 8.
- Kohyama, Naoki,Katashima, Tomoyuki,Yamamoto, Yukio
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p. 2799 - 2804
(2007/10/03)
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- Anti-HCV nucleoside derivatives
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The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.
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- Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase
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The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.
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- Synthesis and conformational studies of d(TpA) and r(UpA) conjugated with histamine and ethylenediamine
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Dinucleotides (Figure 1b-d) possessing histamino/ethylenediamino substituents at C8 of adenine have been synthesised for modelling the molecular interactions that occur at catalytic site of nucleases. These compounds have been designed for putative molecular recognition of internucleotide phosphate by a complementary group (imidazole/-NH2) in the pendant C-8 side chains. 1H NMR spectroscopic analysis of synthesised model compounds indicate that C-8 modification leads to increase in percentage of S conformation of modified sugar while still maintaining an anti glycosyl torsion as in unmodified analog d(TpA). The C-8 side chain functionality (histamine/ethylenediamine) is probably involved in intramolecular interaction (electrostatic/ hydrogen bond) with the phosphate and/or 2′OH in (14). Such predisposition of side chain catalytic groups is important in developing appropriate models for active site of nucleases.
- Prakash,Krishna Kumar,Ganesh
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p. 4035 - 4050
(2007/10/02)
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- Synthesis of the nucleosides of uronic acids. I. Methods for the synthesis of 8-substituted adenosine-5'-carboxylic acid and its esters
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Various methods for the synthesis of 8-substituted adenosine-5'-carboxylic acid and its esters were studied. 8-Bromo-2',3'-O-isopropylideneadenosine-5'-carboxylic acid was synthesized by the oxidation of 8-bromo-2',3'-O-isopropylideneadenosine with potassium permanganate in an alkaline medium. 8-Bromoadenosine-5'-carboxylic acid was obtained under the conditions of controlled acid hydrolysis of the 2',3'-O-isopropylidene protection.Esterification of the acids with alcohols in the presence of thionyl chloride gave the corresponding esters.
- Akhrem, A. A.,Ermolenko, T. M.,Timoshchuk, V. A.
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p. 1639 - 1644
(2007/10/02)
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