- Oxidative conversion of N-dimethylformamidine nucleosides to N-cyano nucleosides
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Reaction of the N-dimethylformamidine (dmf) derivatives of 2'-deoxyguanosine, guanosine, and 2'-deoxyadenosine with iodine and aqueous ammonia gives the corresponding N-cyano nucleosides. This reaction occurs in oligonucleotides under conditions where iodine is retained on the solid support, or in the synthesis column, prior to cleavage with aqueous ammonia. This base modification can be eliminated with lower iodine concentration in the oxidation reagent.
- Mullah,Mullah, Bashar,Andrus,Andrus, Alex,Zhao,Zhao, Hong,Jones,Jones, Roger A.
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Read Online
- Chemical composition and toxicity of Taiwanese betel quid extract
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In this genotoxic study, the Ames Salmonella microsome test showed that an aqueous extract of betel quid did not induce mutagenicity in Salmonella typhimurium strains TA98 and TA100. Mammalian cell studies (Chinese hamster ovary K1 cell; CHO-K1 cell) revealed that only higher concentrations (100 and 1000μg/ml) of aqueous extract weekly increased the frequencies of sister-chromatid exchange (SCE) in the absence of S9. Animal (male Sprague-Dawley rat) studies showed that low-dose feeding (0.53g dry aqueous extract/kg diet) significantly increased the activities of glutathione (GSH) peroxidase and cytoplasmic glutathione S-transferase (cGST) of liver, high-dose feeding (26.5g dry aqueous extract/kg diet) lowered the contents of GSH and total glutathione. The effect of an aqueous extract of betel quid on the oxidation of 2'-deoxyguanosine (2'-dG) to 8-hydroxy-2'-deoxyguanosine (8-OH-dG) evaluated that this aqueous extract may act as a pro-oxidant at lower dosage and may be dependent on the iron ions in the model system. However, the aqueous extract of betel quid showed antioxidant activity at higher doses by the ability of the scavenging effect of the hydroxyl radicals. Copyright (C) 1999 Elsevier Science B.V.
- Wang,Su,Lii
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Read Online
- Independent Generation and Time-Resolved Detection of 2′-Deoxyguanosin-N2-yl Radicals
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Guanine radicals are important reactive intermediates in DNA damage. Hydroxyl radical (HO.) has long been believed to react with 2′-deoxyguanosine (dG) generating 2′-deoxyguanosin-N1-yl radical (dG(N1-H).) via addition to the nucleob
- Dai, Xiaojuan,Greenberg, Marc M.,Su, Hongmei,Zheng, Liwei
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Read Online
- Independent Generation and Reactivity of 2′-Deoxyguanosin- N1-yl Radical
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2′-Deoxyguanosin-N1-yl radical (dG(N1-H)?) is the thermodynamically favored one-electron oxidation product of 2′-deoxyguanosine (dG), the most readily oxidized native nucleoside. dG(N1-H)? is produced by the formal dehydration of a hydroxyl radical adduct of dG as well as by deprotonation of the corresponding radical cation. dG(N1-H)? were formed as a result of the indirect and direct effects of ionizing radiation, among other DNA damaging agents. dG(N1-H)? was generated photochemically (λmax = 350 nm) from an N-aryloxy-naphthalimide precursor (3). The quantum yield for photochemical conversion of 3 is ～0.03 and decreases significantly in the presence O2, suggesting that bond scission occurs from a triplet excited state. dG is formed quantitatively in the presence of excess β-mercaptoethanol. In the absence of a reducing agent, dG(N1-H)? oxidizes 3, decreasing the dG yield to ～50%. Addition of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) as a sacrificial reductant results in a quantitative yield of dG and two-electron oxidation products of 8-oxodGuo. N-Aryloxy-naphthalimide 3 is an efficient and high-yielding photochemical precursor of dG(N1-H)? that will facilitate mechanistic studies on the reactivity of this important reactive intermediate involved in DNA damage.
- Zheng, Liwei,Greenberg, Marc M.
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p. 8665 - 8672
(2020/07/03)
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- Thermodynamic Reaction Control of Nucleoside Phosphorolysis
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Nucleoside analogs represent a class of important drugs for cancer and antiviral treatments. Nucleoside phosphorylases (NPases) catalyze the phosphorolysis of nucleosides and are widely employed for the synthesis of pentose-1-phosphates and nucleoside analogs, which are difficult to access via conventional synthetic methods. However, for the vast majority of nucleosides, it has been observed that either no or incomplete conversion of the starting materials is achieved in NPase-catalyzed reactions. For some substrates, it has been shown that these reactions are reversible equilibrium reactions that adhere to the law of mass action. In this contribution, we broadly demonstrate that nucleoside phosphorolysis is a thermodynamically controlled endothermic reaction that proceeds to a reaction equilibrium dictated by the substrate-specific equilibrium constant of phosphorolysis, irrespective of the type or amount of NPase used, as shown by several examples. Furthermore, we explored the temperature-dependency of nucleoside phosphorolysis equilibrium states and provide the apparent transformed reaction enthalpy and apparent transformed reaction entropy for 24 nucleosides, confirming that these conversions are thermodynamically controlled endothermic reactions. This data allows calculation of the Gibbs free energy and, consequently, the equilibrium constant of phosphorolysis at any given reaction temperature. Overall, our investigations revealed that pyrimidine nucleosides are generally more susceptible to phosphorolysis than purine nucleosides. The data disclosed in this work allow the accurate prediction of phosphorolysis or transglycosylation yields for a range of pyrimidine and purine nucleosides and thus serve to empower further research in the field of nucleoside biocatalysis. (Figure presented.).
- Kaspar, Felix,Giessmann, Robert T.,Neubauer, Peter,Wagner, Anke,Gimpel, Matthias
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supporting information
p. 867 - 876
(2020/01/24)
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- Solid-phase synthesis and structural characterisation of phosphoroselenolate-modified DNA: A backbone analogue which does not impose conformational bias and facilitates SAD X-ray crystallography
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Oligodeoxynucleotides incorporating internucleotide phosphoroselenolate linkages have been prepared under solid-phase synthesis conditions using dimer phosphoramidites. These dimers were constructed following the high yielding Michaelis-Arbuzov (M-A) reaction of nucleoside H-phosphonate derivatives with 5′-deoxythymidine-5′-selenocyanate and subsequent phosphitylation. Efficient coupling of the dimer phosphoramidites to solid-supported substrates was observed under both manual and automated conditions and required only minor modifications to the standard DNA synthesis cycle. In a further demonstration of the utility of M-A chemistry, the support-bound selenonucleoside was reacted with an H-phosphonate and then chain extended using phosphoramidite chemistry. Following initial unmasking of methyl-protected phosphoroselenolate diesters, pure oligodeoxynucleotides were isolated using standard deprotection and purification procedures and subsequently characterised by mass spectrometry and circular dichroism. The CD spectra of both modified and native duplexes derived from self-complementary sequences with A-form, B-form or mixed conformational preferences were essentially superimposable. These sequences were also used to study the effect of the modification upon duplex stability which showed context-dependent destabilisation (-0.4 to-3.1 °C per phosphoroselenolate) when introduced at the 5′-Termini of A-form or mixed duplexes or at juxtaposed central loci within a B-form duplex (-1.0 °C per modification). As found with other nucleic acids incorporating selenium, expeditious crystallisation of a modified decanucleotide A-form duplex was observed and the structure solved to a resolution of 1.45 ?. The DNA structure adjacent to the modification was not significantly perturbed. The phosphoroselenolate linkage was found to impart resistance to nuclease activity.
- Conlon, Patrick F.,Eguaogie, Olga,Wilson, Jordan J.,Sweet, Jamie S. T.,Steinhoegl, Julian,Englert, Klaudia,Hancox, Oliver G. A.,Law, Christopher J.,Allman, Sarah A.,Tucker, James H. R.,Hall, James P.,Vyle, Joseph S.
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p. 10948 - 10957
(2019/12/23)
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- Oxidation of 1-N2-etheno-2′-deoxyguanosine by singlet molecular oxygen results in 2′-deoxyguanosine: A pathway to remove exocyclic DNA damage?
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Exocyclic DNA adducts are considered as potential tools for the study of oxidative stress-related diseases, but an important aspect is their chemical reactivity towards oxidant species. We report here the oxidation of 1-N2-etheno-2′-deoxyguanosine (1,N2-?dGuo) by singlet molecular oxygen (1O2) generated by a non-ionic water-soluble endoperoxide [N,N′-di(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide endoperoxide (DHPNO2)] and its corresponding oxygen isotopically labeled [18O]-[N,N′-di(2,3-dihydroxypropyl)-1,4- naphthalenedipropanamide endoperoxide (DHPN18O2)], and by photosensitization with two different photosensitizers [methylene blue (MB) and Rose Bengal (RB)]. Products detection and characterization were achieved using high performance liquid chromatography (HPLC) coupled to ultraviolet and electrospray ionization (ESI) tandem mass spectrometry, and nuclear magnetic resonance (NMR) analyses. We found that dGuo is regenerated via reaction of 1O2 with the ?-linkage, and we propose a dioxetane as an intermediate, which cleaves and loses the aldehyde groups as formate residues, or alternatively, it generates a 1,2-ethanediol adduct. We also report herein the quenching rate constants of 1O2 by 1,N2-?dGuo and other etheno modified nucleosides. The rate constant (kt) values obtained for etheno nucleosides are comparable to the kt of dGuo. From these results, we suggest a possible role of 1O2 in the cleanup of etheno adducts by regenerating the normal base.
- Martinez, Glaucia Regina,Brum, Hulyana,Sassaki, Guilherme Lanzi,De Souza, Lauro Mera,Loureiro, Ana Paula De Melo,De Medeiros, Marisa Helena Gennari,Di Mascio, Paolo
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p. 859 - 867
(2018/05/04)
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- Hydrogen peroxide-Triggered gene silencing in mammalian cells through boronated antisense oligonucleotides
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Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) involved in various diseases, including neurodegeneration, diabetes, and cancer. Here, we introduce a new approach to use H2O2 to modulate specific gene expression in mammalian cells. H2O2-responsive nucleoside analogues, in which the Watson-Crick faces of the nucleobases are caged by arylboronate moieties, were synthesized. One of these analogues, boronated thymidine (dTB), was incorporated into oligodeoxynucleotides (ODNs) using an automated DNA synthesizer. The hybridization ability of this boronated ODN to complementary RNA was clearly switched in the off-To-on direction upon H2O2 addition. Furthermore, we demonstrated H2O2-Triggered gene silencing in mammalian cells using antisense oligonucleotides (ASOs) modified with dTB. Our approach can be used for the regulation of any gene of interest by the sequence design of boronated ASOs and will contribute to the development of targeted disease therapeutics.
- Mori, Shohei,Morihiro, Kunihiko,Okuda, Takumi,Kasahara, Yuuya,Obika, Satoshi
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p. 1112 - 1118
(2018/02/09)
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- Independent Photochemical Generation and Reactivity of Nitrogen-Centered Purine Nucleoside Radicals from Hydrazines
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Photochemical precursors that produce dA￠ and dG(N2-H)￠ are needed to investigate their reactivity. The synthesis of two 1,1-diphenylhydrazines (1, 2) and their use as photochemical sources of dA￠ and dG(N2-H)￠ is presented. Trapping studies indicate production of these radicals with good fidelity, and 1 was incorporated into an oligonucleotide via solid-phase synthesis. Cyclic voltammetric studies show that reduction potentials of 1 and 2 are lower than those of widely used "hole sinks", e.g., 8-oxodGuo and 7-deazadGuo, to investigate DNA-hole transfer processes. These molecules could be useful (a) as sources of dA￠ and dG(N2-H)￠ at specific sites in oligonucleotides and (b) as "hole sinks" for the study of DNA-hole transfer processes.
- Zheng, Liwei,Lin, Lu,Qu, Ke,Adhikary, Amitava,Sevilla, Michael D.,Greenberg, Marc M.
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supporting information
p. 6444 - 6447
(2017/12/08)
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- PRODUCTION METHOD OF NUCLEOSIDE COMPOUND
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PROBLEM TO BE SOLVED: To provide a production method of a nucleoside compound by which an isotopic labeled nucleoside compound can be produced efficiently. SOLUTION: A production method of a nucleoside compound comprises obtaining a target nucleoside compound by the base exchange reaction of a raw material nucleoside compound and a base in the solution containing a phosphoric acid ion by a nucleoside phosphorylase, wherein the target nucleoside compound is labeled with a stable isotope or a radioisotope. COPYRIGHT: (C)2015,JPOandINPIT
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Paragraph 0032-0033
(2017/03/24)
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- Cytotoxicity of guanine-based degradation products contributes to the antiproliferative activity of guanine-rich oligonucleotides
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Guanine-rich oligonucleotides (GROs) have attracted considerable attention as anticancer agents, because they exhibit cancer-selective antiproliferative activity and can form G-quadruplex structures with higher nuclease resistance and cellular uptake. Recently, a GRO, AS1411 has reached phase II clinical trials for acute myeloid leukemia and renal cell carcinoma. The antiproliferative activity of GROs has been associated with various protein targets; however the real mechanisms of action remain unclear. In this study, we showed evidence that antiproliferative activity of GROs (including AS1411) is mainly contributed by the cytotoxicity of their guanine-based degradation products, such as monophosphate deoxyguanosine (dGMP), deoxyguanosine (dG) and guanine. The GROs with lower nuclease resistance exhibited higher antiproliferative activity. Among nucleotides, nucleosides and nucleobases, only guanine-based compounds showed highly concentration-dependent cytotoxicity. Our results suggest that it is necessary to reconsider the cancer-selective antiproliferative activity of GROs. Since guanine-based compounds are endogenous substances in living organisms, systematic studies of the cytotoxicity of these compounds will provide new information for the understanding of certain diseases and offer useful information for drug design.
- Zhang, Nan,Bing, Tao,Liu, Xiangjun,Qi, Cui,Shen, Luyao,Wang, Linlin,Shangguan, Dihua
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p. 3831 - 3838
(2015/06/25)
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- Formation of 8-S-L-cysteinylguanosine from 8-bromoguanosine and cysteine
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When 8-bromoguanosine was incubated with cysteine at pH 7.4 and 37 C, a previously unidentified product was formed as a major product in addition to guanosine. The product was identified as a cysteine substitution derivative of guanosine at the 8 position, 8-S-l-cysteinylguanosine. The reaction was accelerated under mildly basic conditions. The cysteine adduct of guanosine was fairly stable and decomposed with a half-life of 193 h at pH 7.4 and 37 C. Similar results were observed for incubation of 8-bromo-2′-deoxyguanosine with cysteine. The results suggest that 8-bromoguanine in nucleosides, nucleotides, RNA, and DNA can react with thiols resulting in stable adducts.
- Suzuki, Toshinori,Kosaka, Aya,Inukai, Michiyo
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p. 3864 - 3867
(2013/07/27)
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- Developing a collection of immobilized nucleoside phosphorylases for the preparation of nucleoside analogues: Enzymatic synthesis of arabinosyladenine and 2',3'-dideoxyinosine
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The use of nucleoside phosphorylases (NPs; EC 2.4.2.n) represents a convenient alternative to the chemical route for the synthesis of natural and modified nucleosides. We purified four recombinantly expressed nucleoside phosphorylases from the bacterial pathogens Citrobacter koseri, Clostridium perfringens, and Streptococcus pyogenes (CkPNPI, CkPNPII, CpUP, SpUP) and their substrate specificity was investigated towards either natural pyrimidine or purine nucleosides and some analogues, namely, arabinosyladenine (araA) and 2',3'-dideoxyinosine (ddI). A 2-3 % activity towards these latter compounds (compared to the natural substrates) was observed. Enzyme activities were compared to the specificities obtained for the enzymes pyrimidine nucleoside phosphorylase from Bacillus subtilis (BsPyNP) and purine nucleoside phosphorylase from Aeromonas hydrophila (AhPNPII) previously reported by some of the authors. The enzymes displaying the suitable specificity for the synthesis of araA and ddI were immobilized on aldehyde-agarose. The immobilized preparations were highly stable at alkaline pH and in the presence of methanol or acetonitrile as cosolvent. They were used in the synthesis of araA and ddI by a one-pot, bienzymatic transglycosylation achieving 74 and 44 % conversion, respectively. Something different: Nucleoside phosphorylases are a convenient alternative to the chemical route for the synthesis of natural and modified nucleosides. Four new nucleoside phosphorylases have been prepared, characterized, and tested for their use in biocatalyzed syntheses of araA and ddI (see scheme). A generally applicable immobilization technique has been found to provide active and stable biocatalysts.
- Serra, Immacolata,Ubiali, Daniela,Piskur, Jure,Christoffersen, Stig,Lewkowicz, Elizabeth S.,Iribarren, Adolfo M.,Albertini, Alessandra M.,Terreni, Marco
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p. 157 - 165
(2013/04/24)
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- Phosphorylating reagent-free synthesis of 5′-phosphate oligonucleotides by controlled oxidative degradation of their 5′-end
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The 5′-phosphorylated oligonucleotides (5′-pONs) are currently synthesized using expensive and sensitive modified phosphoramidite reagents. In this work, a simple, cost-effective, efficient, and automatable method is presented, based on the controlled oxidation of the 5′-terminal alcohol followed by a β-elimination reaction. The latter reaction leads to the removal of the terminal 5′-nucleoside and subsequent formation of the 5′-phosphate moiety. Thus, chemical phosphorylation of oligonucleotides (DNA or RNA) is achieved without using modified phosphoramidites.
- Sallamand, Corinne,Miscioscia, Audrey,Lartia, Remy,Defrancq, Eric
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supporting information; body text
p. 2030 - 2033
(2012/06/18)
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- Radical-based alkylation of guanine derivatives in aqueous medium
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The radical-based alkylation of 8-bromoguanosine (1a) and 8-bromo-2′-deoxyguanosine (1b) at the C8 position has been investigated in aqueous solutions. Alkyl radicals were generated by scavenging of the primary species of γ-radiolysis by the alcohol substrate. These reactions result in the efficient formation of intermolecular C-C bonds in aqueous media, by using the reactivity of α-hydroxyalkyl radicals derived from alcohols with 1a and 1b. A mechanism for the formation of C8 guanine alkylated adducts has been proposed, based on the quantification of radiation chemical yields for the disappearance of starting material and the formation of all products. Two α-hydroxyalkyl radicals are needed to form an alkylated guanine, the first one adding to C8 followed by ejection of Br- with formation of guanyl adduct and the second one acting as reducing agent of the guanyl adduct.
- Chatgilialoglu, Chryssostomos,Caminal, Clara,Mulazzani, Quinto G.
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scheme or table
p. 3494 - 3498
(2011/06/25)
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- 5-Fluoro-4-thiouridine phosphoramidite: New synthon for introducing photoaffinity label into oligodeoxynucleotides
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The synthesis of phosphoramidite of 5-fluoro-4-thio-2′-O- methyluridine is described. An appropriate set of protecting groups was optimized including the 4-thio function introduced via 4-triazolyl as the 4-(2-cyanoethyl)thio derivative, and the t-butyldimethyl silyl for 2′ and 3′ hydroxyl protection, enabling efficient synthesis of the phosphoramidite. These protecting groups prevented unwanted side reactions during oligonucleotide synthesis. The utility of the proposed synthetic route was proven by the preparation of several oligonucleotides via automated synthesis. Photochemical experiments confirmed the utility of the synthon.
- Milecki, Jan,Nowak, Joanna,Skalski, Bohdan,Franzen, Stefan
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experimental part
p. 6098 - 6106
(2011/11/07)
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- Site-directed spin-labeling of DNA by the azide-alkyne 'Click' reaction: Nanometer distance measurements on 7-deaza-2′-deoxyadenosine and 2′-deoxyuridine nitroxide conjugates spatially separated or linked to a 'dA-dT' base pair
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Nucleobase-directed spin-labeling by the azide-alkyne 'click' (CuAAC) reaction has been performed for the first time with oligonucleotides. 7-Deaza-7-ethynyl-2′-deoxyadenosine (1) and 5-ethynyl-2′- deoxyuridine (2) were chosen to incorporate terminal triple bonds into DNA. Oligonucleotides containing 1 or 2 were synthesized on a solid phase and spin labeling with 4-azido-2,2,6,6-tetramethylpiperidine 1-oxyl (4-azido-TEMPO, 3) was performed by post-modification in solution. Two spin labels (3) were incorporated with high efficiency into the DNA duplex at spatially separated positions or into a 'dA-dT' base pair. Modification at the 5-position of the pyrimidine base or at the 7-position of the 7-deazapurine residue gave steric freedom to the spin label in the major groove of duplex DNA. By applying cw and pulse EPR spectroscopy, very accurate distances between spin labels, within the range of 1-2nm, were measured. The spin-spin distance was 1.8A±0. 2nm for DNA duplex 17(dA7,10)·11 containing two spin labels that are separated by two nucleotides within one individual strand. A distance of 1.4A±0.2nm was found for the spin-labeled 'dA-dT' base pair 15(dA7)·16(dT6). The 'click' approach has the potential to be applied to all four constituents of DNA, which indicates the universal applicability of the method. New insights into the structural changes of canonical or modified DNA are expected to provide additional information on novel DNA structures, protein interaction, DNA architecture, and synthetic biology. 'Clicked' DNA spin labels: Spin labels (spheres in the figure) have been incorporated by click chemistry into DNA duplexes at spatially separated positions or into a 'dA-dT' base pair with high efficiency. Very accurate distances between spin labels, within a range of 1-2nm, were measured by continuous wave and pulse EPR spectroscopy. Copyright
- Ding, Ping,Wunnicke, Dorith,Steinhoff, Heinz-Juergen,Seela, Frank
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supporting information; scheme or table
p. 14385 - 14396
(2011/03/22)
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- Synthesis of oligodeoxynucleotides using fully protected Deoxynucleoside 3c-Phosphoramidite building blocks and base recognition of Oligodeoxynucleotides incorporating N3-Cyano-Ethylthymine
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Oligodeoxynucleotide (ODN) synthesis, which avoids the formation of side products, is of great importance to biochemistry-based technology development. One side reaction of ODN synthesis is the cyanoethylation of the nucleobases. We suppressed this reaction by synthesizing ODNs using fully protected deoxynucleoside 3c-phosphoramidite building blocks, where the remaining reactive nucleobase residues were completely protected with acyl-, diacyl-, and acyl-oxyethylene-type groups. The detailed analysis of cyanoethylation at the nucleobase site showed that N3-protection of the thymine base efficiently suppressed the Michael addition of acrylonitrile. An ODN incorporating N3-cyanoethylthymine was synthesized using the phosphoramidite method, and primer extension reactions involving this ODN template were examined. As a result, the modified thymine produced has been proven to serve as a chain terminator.
- Tsunoda, Hirosuke,Kudo, Tomomi,Ohkubo, Akihiro,Seio, Kohji,Sekine, Mitsuo
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experimental part
p. 7509 - 7531
(2011/02/28)
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- Photolysis and thermolysis of platinum(IV) 2,2′-bipyridine complexes lead to identical platinum(II)-DNA adducts
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Two PtIV and two Pt11 complexes containing a 2,2′-bipyridine ligand were treated with a short DNA oligonucleotide under light irradiation at 37 °C or in the dark at 37 and 50 °C. Photolysis and thermolysis of the PtIV complexes led to spontaneous reduction of the PtIV to the corresponding PtII complexes and to binding of PtII 2,2′-bipyridine complexes to N7 of guanine. When the reduction product was [Pt(bpy)Cl2], formation of bis-oligonucleotide adducts was observed, whereas [Pt(bpy)(MeNH 2)Cl]+ gave monoad- ducts, with chloride ligands substituted in both cases. Neither in the dark nor under light irradiation was the reductive elimination process of these PtIV complexes accompanied by oxidative DNA damage. This work raises the question of the stability of photoacti- vatable PtIV complexes toward moderate heating conditions.
- Loup, Christophe,Tesouro Vallina, Ana,Coppel, Yannick,Letinois, Ulla,Nakabayashi, Yasuo,Meunier, Bernard,Lippert, Bernhard,Pratviel, Genevieve
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experimental part
p. 11420 - 11431
(2010/11/24)
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- Radiation-induced formation of purine 5′,8-cyclonucleosides in isolated and cellular DNA: High stereospecificity and modulating effect of oxygen
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The present work is aimed at gaining conclusive mechanistic insights into the radiation-induced formation of the 5′R and 5′S diastereomers of both adenine and guanine 5′,8-cyclo-2′-deoxyribonucleosides, with emphasis on the delineation of the inhibitory effect of O2 in isolated and cellular DNA. The levels of purine 5′,8-cyclo-2′- deoxyribonucleosides as assessed by HPLC-MS/MS were found to decrease steadily with the increase of O2 concentration, the 5′,8-cyclo-2′- deoxyguanosine being produced more efficiently than the 5′,8-cyclo- 2′-deoxyadenosine for low O2 concentrations. A high stereoselectivity was observed in the intramolecular addition of the C5′ radical to the C8 of the purine leading, after the creation of the C5′-C8 bond and a subsequent oxidation step, to the predominant formation of the 5′R diastereomer for both purine 5′,8-cyclonucleosides. The reduced formation yield of the 4 tandem lesions in the presence of O2 explains, at least partly, the low efficiency of radiation-induced yields of the purine 5′,8-cyclo-2′-deoxyribonucleosides in cellular DNA, which are about two orders of magnitude lower than the previously reported data obtained from HPLC-MS analysis. The Royal Society of Chemistry 2010.
- Belmadoui, Nourreddine,Boussicault, Fabien,Guerra, Maurizio,Ravanat, Jean-Luc,Chatgilialoglu, Chryssostomos,Cadet, Jean
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experimental part
p. 3211 - 3219
(2010/08/21)
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- Enzymatic transglycosylation of natural and modified nucleosides by immobilized thermostable nucleoside phosphorylases from Geobacillus stearothermophilus
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Natural and modified purine nucleosides have been synthesized using the recombinant thermostable enzymes purine nucleoside phosphorylase II (E. C. 2.4.2.1) and pyrimidine nucleoside phosphorylase (E. C. 2.4.2.2) from Geobacillus stearothermophilus B-2194. The enzymes were produced in recombinant E. coli strains and covalently immobilized on aminopropylsilochrom AP-CPG-170 after heating the cell lysates and the removal of coagulated thermolabile proteins. The resulting preparations of thermostable nucleoside phosphorylases retained a high activity after 20 reuses in nucleoside transglycosylation reactions at 70-75°C with a yield of the target products as high as 96%. Owing to the high catalytic activity, thermal stability, the ease of application, and the possibility of repeated use, the immobilized preparations of thermostable nucleoside phosphorylases are suitable for the production of pharmacologically important natural and modified nucleosides.
- Taran,Verevkina,Feofanov,Miroshnikov
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experimental part
p. 739 - 745
(2010/08/07)
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- A blocked diketo form of avobenzone: Photostability, photosensitizing properties and triplet quenching by a triazine-derived UVB-filter
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Novel sunscreens are required providing active protection in the UVA and UVB regions. On the other hand, there is an increasing concern about the photosafety of UV filters, as some of them are not sufficiently photostable. Avobenzone is one of the most fr
- Paris, Cecilia,Lhiaubet-Vallet, Virginie,Jimenez, Oscar,Trullas, Carles,Miranda, Miguel Angel
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experimental part
p. 178 - 184
(2009/04/10)
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- Photolabile N-hydroxypyrid-2(1H)-one derivatives of guanine nucleosides: A new method for independent guanine radical generation
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One-electron oxidized guanine is an important reactive intermediate in the formation of oxidatively generated damage in DNA and a variety of methods have been utilized for the abstraction of a single electron from the guanine moiety. In this study, an alt
- Kaloudis, Panagiotis,Paris, Cecilia,Vrantza, Despoina,Encinas, Susana,Perez-Ruiz, Raul,Miranda, Miguel A.,Gimisis, Thanasis
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supporting information; experimental part
p. 4965 - 4972
(2010/02/16)
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- DNA interstrand cross-link formation by the 1,4-dioxobutane abasic lesion
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The oxidized abasic lesion 5′-(2-phosphoryl-1,4-dioxobutane) (DOB) is produced concomitantly with a single-strand break by a variety of DNA-damaging agents that abstract a hydrogen atom from the C5′-position. Independent generation of the DOB lesion in DN
- Guan, Lirui,Greenberg, Marc M.
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supporting information; experimental part
p. 15225 - 15231
(2010/01/29)
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- A kinetic study of the rat liver adenosine kinase reverse reaction
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Adenosine kinase is an enzyme catalyzing the reaction: adenosine + ATP → AMP + ADP. We studied some biochemical properties not hitherto investigated and demonstrated that the reaction can be easily reversed when coupled with adenosine deaminase, which transforms adenosine into inosine and ammonia. The overall reaction is: AMP + ADP → ATP + inosine + NH3. The exoergonic ADA reaction shifts the equilibrium and fills the energy gap necessary for synthesis of ATP. This reaction could be used by cells under particular conditions of energy deficiency and, together with myokinase activity, may help to restore physiological ATP levels. Copyright Taylor & Francis Group, LLC.
- Vannoni,Giglioni,Santoro,Aceto,Marinello,Leoncini
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p. 872 - 875
(2008/12/21)
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- Flow injection amperometric detection of 2′-deoxyguanosine at a ruthenium oxide hexacyanoferrate modified electrode
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A ruthenium oxide hexacyanoferrate (RuOHCF) modified electrode was developed. Hydrodynamic voltammetry was employed to demonstrate the remarkable electrocatalytic activity toward the oxidation of 2′-deoxyguanosine. The RuOHCF modified electrode was used as amperometric detector for 2′-deoxyguanosine determination in a FIA apparatus. The influence of various experimental conditions was explored for optimum analytical performance, and at these experimental conditions, the method exhibited a linear response range to 2′-deoxyguanosine extending from 3.8 to 252 μmol L -1 with detection limit of 94 nmol L-1. Applications in DNA samples were examined, and the results for determination of 2′-deoxyguanosine were in good agreement with those obtained by HPLC analysis. Studies on the kinetics of the in vitro consumption of 2′-deoxyguanosine by acetaldehyde were also performed.
- Paixao, Thiago R. L. C.,Garcia, Camila C. M.,Medeiros, Marisa H. G.,Bertotti, Mauro
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p. 5392 - 5398
(2008/02/10)
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- Production method of 2'-deoxyguanosine compound
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The present invention provides a production method of a 2'-deoxyguanosine compound represented by the following formula (2), which includes a step of desulfurization reaction of an 8,2'-anhydro-8-mercapto-9-β-arabinofuranosylguanine compound represented by the following formula (1) in a solvent in the presence of a base using nickel or a nickel alloy. wherein R1, R2, R4 and R5 are each independently a hydrogen atom or a hydroxyl-protecting group, and R3 and R6 are hydrogen atoms or amino-protecting groups.
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- Process for producing 2'-deoxyguanosine
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The invention provides a process for producing 2′-deoxyguanosine, characterized in that the process includes reacting one compound selected from the group consisting of guanosine, guanosine 5′-monophosphate, and 2-amino-6-substituted purine with 2′-deoxynucleoside in the presence of nucleoside deoxyribosyl transferase and a hydrolase. According to the process of the present invention, 2′-deoxyguanosine can be synthesized efficiently from inexpensive and easily available starting materials. Since no guanosine, which disturbs purification, is virtually present in a reaction mixture, isolation and purification of 2′-deoxyguanosine can be performed in a very simple manner. Thus, the process for producing 2′-deoxyguanosine is practical.
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Page/Page column 7
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- A new protecting group for the exocyclic amino groups of nucleosides
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A new protecting group has been developed for the exocyclic amino groups of nucleosides that occur in DNA. 3-Phenyl-[{N-(2-trimethylsilyl-ethoxycarbonyl)- 2-amino}]-propanoic acid used as the protective agent.
- Varaprasad, Chamakura V.N.S.,Johnson, Francis
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p. 2163 - 2165
(2007/10/03)
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- Synthesis of 2′-deoxynucleosides by transglycosylation with new immobilized and stabilized uridine phosphorylase and purine nucleoside phosphorylase
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Multimeric uridine phosphorylase (UP) and purine nucleoside phosphorylase (PNP) of Bacillus subtilis have been expressed from genes cloned in Escherichia coli, purified, characterized, immobilized and stabilized on solid support. A new immobilization strategy has been developed for UP onto Sepabeads coated with polyethyleneamine followed by cross-linking with aldehyde-dextran. PNP has been immobilized onto glyoxyl-agarose. At pH 10 and 45°C these derivatives catalyzed the transglycosylation of 2′-deoxyuridine to 2′-deoxyguanosine in high yield (92%). Under the same conditions the not immobilized enzymes were promptly inactivated.
- Ubiali, Daniela,Rocchietti, Silvia,Scaramozzino, Francesca,Terreni, Marco,Albertini, Alessandra M.,Fernandez-Lafuente, Roberto,Guisan, Jose Manuel,Pregnolato, Massimo
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p. 1361 - 1366
(2007/10/03)
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- Enzymatic synthesis of 2'-deoxyguanosine with nucleoside deoxyribosyltransferase-II.
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Nucleoside deoxyribosyltransferase-II (NdRT-II) of Lactobacillus helveticus, which catalyzes the transfer of a glycosyl residue from a donor deoxyribonucleoside to an acceptor base, has a broad specificity for the acceptor bases. Six-substituted purines were found to be substrates as acceptor bases for NdRT-II. Using this property of the enzyme, we established a practical procedure for enzymatic synthesis of 2'-deoxyguanosine (dGuo), consisting of the transglycosylation from thymidine to 6-substituted purine (2-amino-6-chloropurine; ACP) instead of natural guanine and the conversion of 2-amino-6-chloropurine-2'-deoxyriboside (ACPdR) to dGuo with bacterial adenosine deaminase. Through the successive reactions, dGuo was synthesized in high yield.
- Okuyama, Kiyoshi,Shibuya, Susumu,Hamamoto, Tomoki,Noguchi, Toshitada
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p. 989 - 995
(2007/10/03)
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- Facile synthesis of oligonucleotides on solid support using pyridine derivatives for amino and phosphate protection
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The picolinoyl group has been used for amino protection in the case of all the three deoxynucleosides-dC, dA and dG, and good yields of N-protected nucleosides are obtained. This pyridine derivative along with another pyridine derivative, viz. (α-pyridyl) methyl, an autocatalytic phosphate protecting group, has been used successfully in the synthesis of two oligonucleotides, d(TACGTTTTGCT) and d(ACCGATATCGT) following solid phase methodology. The good yields of these 11-mers (48 and 45%, respectively) are attributed to the greater solubilising effect generated due to the combination of these two groups. The structures of these oligomers have been confirmed by enzymatic hydrolysis with snake venom phosphodiesterase followed by alkaline phosphatase.
- Sinha, Sarika,Singh, Ramendra K.
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p. 1696 - 1700
(2007/10/03)
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- Smooth and selective formation of the cyclic 1,N2-propano adducts in the reactions of guanine nucleosides and nucleotides with acetaldehyde
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The treatment of guanine nucleosides and nucleotides with excess acetaldehyde in pH 8.0 phosphate buffer containing a basic amino acid such as arginine and lysine resulted in the smooth and selective formation of the corresponding cyclic 1,N2-propano adducts even under mild conditions.
- Sako, Magoichi,Yaekura, Isamu,Deyashiki, Yoshihiro
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p. 6701 - 6703
(2007/10/03)
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- Reaction of malondialdehyde-DNA adducts with hydrazines - Development of a facile assay for quantification of malondialdehyde equivalents in DNA
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Malondialdehyde is a ubiquitous product of lipid peroxidation that reacts with DNA to form premutagenic lesions. Principal among them is pyrimido-[1,2-α]purin-10(3H)-one (M1G). M1G has recently been found to be a reactive electrophile in DNA that couples with amines at basic pH or hydroxylamines at neutral pH. We explored the reaction of M1G with hydrazines because of the possibility that the latter could act as bifunctional nucleophiles to strip the malondialdehyde equivalent from DNA. Pentafluorophenylhydrazine reacted rapidly with M1G to form a hydrazone conjugate. This hydrazone was stable at room temperature and did not cyclize to form the corresponding pyrazole. In contrast, phenylhydrazine and benzylhydrazine reacted with M1G to form phenylpyrazole and benzylpyrazole, respectively. Pentafluorobenzylhydrazine reacted rapidly with M1G to form pentafluorobenzylpyrazole and dG in near quantitative yield. This reaction formed the basis for a quantitative assay for the presence of M1G or M1G equivalents in DNA or protein that utilized gas chromatography/negative chemical ionization mass spectrometry. The assay was extended to the oxopropenyl donors, M1A, base propenal, and Nε-3-oxopropenyl-lysine. Analysis of DNA treated with bleomycin demonstrated a linear increase in the level of oxopropenyl groups that plateaued at approximately 1 oxopropenyl group/100 bases at a bleomycin concentration of 200 μM. Parallel analysis of M1G in the samples revealed that this adduct represents a small fraction of the total oxopropenyl units generated in DNA by treatment with bleomycin.
- Otteneder, Michael,Plastaras, John P.,Marnett, Lawrence J.
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p. 312 - 318
(2007/10/03)
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- Photolabile groups for exocyclic amino and O6/N-1 lactam protection in oligonucleotide synthesis
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The use of o-nitrobenzyloxycarbonyl (nCbz) for direct protection of exocyclic amino function of nucleosides viz. adenosine, cytidine and deoxyguanosine using o-nitrobenzyl-p-nitrophenyl carbonate as a reagent and O6-derivatization of deoxyguanosine with o-nitrobenzyl (nBzl) using o-nitrobenzyldiazomethane as a reagent is being reported. Both these protected groups could be cleaved by irradiation at 354nm to yield valuable building blocks for oligonucleotide synthesis.
- Misra, Arvind,Tripathi, Snehlata,Misra, Krishna
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p. 1454 - 1459
(2007/10/03)
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- Process for selectively producing 1-phosphorylated sugar derivative anomer and process for producing nucleoside
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A desired isomer is selectively prepared by phosphorolyzing and isomerizing an anomer mixture of a 1-phosphorylated saccharide derivative while crystallizing one of the isomers to displace the equilibrium. Furthermore, using the action of a nucleoside phosphorylase, a nucleoside is prepared from the 1-phosphorylated saccharide derivative obtained and a base with improved stereoselectivity and a higher yield. This process is an anomer-selective process for preparing a 1-phosphorylated saccharide derivative and a nucleoside.
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- Large-scale manufacturing of all four 2′-deoxynucleosides via novel strategies including a chemo-enzymatic process
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A chemical synthesis of 2-deoxyribose-1-phosphate 2 and its enzymatic conversion into purine 2′-deoxynucleosides (dNus) are shown. Besides the chemoenzymatic process for purine dNus, a modified process for practical dC preparation is also established. Consequently, a series of practical manufacturing processes of all four dNus have been realized via novel strategies.
- Komatsu,Awano,Tanikawa,Itou,Ikeda
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p. 1291 - 1293
(2007/10/03)
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- Stereospecific synthesis of oligonucleotides containing crotonaldehyde adducts of deoxyguanosine
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Crotonaldehyde reacts with DNA to form two diastereomeric 1,N2 cyclic adducts of deoxyguanosine. A synthesis of the two diastereomeric deoxynucleosides has been achieved by reaction of mixed diastereomers of 4-amino-1,2-pentanediol with 2-fluoro-O6-(trimethylsilylethyl)-deoxyinosine. The resulting N2-(1-methyl-3,4-dihydroxybutyl)-deoxyguanosine was treated with NaIO4, cleaving the vicinal diol to the aldehyde. Spontaneous cyclization gave the two diastereomers of the crotonaldehyde-adducted nucleoside that were readily separated by HPLC. The absolute configurations were assigned by an enantiospecific synthesis of one diastereomer from (S)-3-aminobutanoic acid. The synthetic strategy has been extended to preparation of a site-specifically adducted oligonucleotide by reaction of the mixed diastereomers of 4-amino-1,2-pentanediol with an 8-mer oligonucleotide containing 2-fluoro-O6-(trimethylsilylethyl)-deoxyinosine. The diastereomeric oligonucleotides were separated by HPLC and absolute configurations of the adducts were established by enzymatic digestion to the adducted nucleosides.
- Nechev,Kozekov,Harris,Harris
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p. 1506 - 1512
(2007/10/03)
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- Synthesis and characterization of nucleosides and oligonucleotides with a benzo[a]pyren-6-ylmethyl adduct at adenine N6 or guanine N2
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Benzo[a]pyrene (1) can be converted to reactive electrophilic species by a number of metabolic pathways, of which the route to the mutagenic and carcinogenic diol epoxide(s) is the best studied. An alternative and interesting pathway to a highly genotoxic electrophile is through alkylation at the 6 position to 6-methylbenzo[a]pyrene (2) followed by oxidation of the methyl group to give 6-hydroxymethylbenzo[a]pyrene (3). Esterification of 3, especially to sulfate ester 4, gives compounds which are both mutagenic and carcinogenic. The major DNA adduct identified from exposure of rats and mice to 4 is the guanine N2 adduct [2′-deoxy-N2-(benzo-[a]pyren-6-ylmethyl)guanosine,5] which is also formed via activation of 2 to a radical cation species by horseradish peroxidase/H2O2 or iodine. To study the biological and structural properties of this adduct and the analogous adenine N6 adduct (6), a nonbiomimetic synthesis of the adducted nucleosides 5 and 6 has been developed and has been extended to preparation of oligonucleotides containing 5 or 6 at a single site.
- Kim,Cooper,Nechev,Harris,Harris
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p. 1306 - 1314
(2007/10/03)
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- Synthesis and deprotection of oligonucleotides under aprotic conditions
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(matrix presented) Oligonucleotides containing an alkali-labile nucleotide are synthesized and deprotected using a synthetic method that eliminates the use of Bronsted acid and base. The development of a new family of exocyclic amine-protecting groups is an integral component of this approach.
- Chen, Tongqian,Fu, Jiasheng,Greenberg, Marc M.
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p. 3691 - 3694
(2007/10/03)
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- Direct strand cleavage via furanyladenine formation in anaerobic photoirradiation of 5-bromouracil-containing oligonucleotides
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The mechanism of direct strand cleavage induced by anaerobic irradiation of 5-bromouracil ((Br)U)-containing DNA was investigated. The formation of an oligonucleotide fragment containing 3'-furanyladenine end like 5 was observed as a major photoproduct for the direct strand breaks. (C) 2000 Elsevier Science Ltd.
- Fujimoto,Ikeda,Saito
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p. 6455 - 6459
(2007/10/03)
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- Photocleavable protecting groups as nucleobase protections allowed the solid-phase synthesis of base-sensitive SATE-prooligonucleotides
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The first synthesis of oligodeoxynucleotide heteropolymers carrying base-sensitive S-pivaloylthioethyl (t-Bu-SATE) phosphotriester linkages has been performed. It is based on the use of 6-nitroveratryloxycarbonyl (NVOC) and 2,2'-bis(2-nitrophenyl)ethoxycarbonyl (diNPEOC) groups as nucleobase protections in combination with photolysis deprotection. The synthesis was realized using the phosphoramidite approach on solid support bearing a 1-(o- nitrophenyl)-1,3-propanediol linker. The removal of the protecting groups and the cleavage of the oligonucleotides from the solid support were accomplished in a single photolysis procedure upon UV irradiation at wavelengths > 300 nm. Faster deprotection rates were observed for diNPEOC-protected nucleosides and oligomers than with NVOC-protected ones. The synthesis of pentanucleoside t- Bu-SATE-phosphotriesters d((5')TpCpCpCpTp(3')), d((5')TpApApApAp(3')), and d((5')TpGpGpGpTp(3')) and of dodecanucleoside t-Bu-SATE-phosphotriesters and -phosphorothioate d((5')ApCpApCpCpCpApApTpTpCpTp(3')) and d((5')ApGpApApTpTpGpGpGpTpGpTp(3')) demonstrated the efficiency of the method.
- Alvarez, Karine,Vasseur, Jean-Jacques,Beltran, Thierry,Imbach, Jean-Louis
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p. 6319 - 6328
(2007/10/03)
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- Design and synthesis of a new type of modified nucleoside for triple helix-mediated adenine-thymine base pair recognition: Formation of hydrogen bonds to the far-side adenine
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We have synthesized a new class of modified nucleoside, X, that could recognize adenine-thymine base pairs. They were designed to form the triple helix of A-T-X motif, where X forms hydrogen bonds to the N7 and NH2 of the far-side adenine in the major groove. Compounds 1 and 2 are a new type of triplex-forming modified nucleoside which are expected to act as DNA cleaving agents through the p-nitrophenyl group.
- Saito, Akiko,Kuroda, Reiko
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p. 4837 - 4840
(2007/10/03)
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- Debromination of 8-bromo-2'-deoxyguanosine by methylene blue and visible light
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Debromination of 8-bromo-2'-deoxyguanosine was accomplished in high yield under neutral conditions in aqueous methanol by irradiating with visible light in the presence of methylene blue as a sensitizer and triethylamine as an electron donor. The method can be extended for the debromination of other bromoaromatic compounds.
- Venkatarangan, Lata,Yang, Dan-Hui,Epling, Gary A.,Basu, Ashis K.
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p. 1441 - 1444
(2007/10/03)
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- Selective hydrolysis of nucleotides to nucleosides and free bases
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The kinetics of the hydrolysis of 2'-deoxyadenosine-5'-monophosphoric acid (dAMP), 2'-deoxycytidine-5'-monophosphoric acid (dCMP), 2'-deoxyguanosine-5'-monophosphoric acid (dGMP) and tymidine-5'-monophosphoric acid (dTMP) was studied in the presence of Xanthomonas maltophilia [1]. The reaction products are nucleosides: 2'-deoxyadenosine (dA), 2'-deoxycytidine (dC), 2'-deoxyguanosine (dG) and tymidine (dT), respectively, or the respective free bases. Hydrolysis of dTMP and dGMP proceeded stepwise according to the sequence: nucleotide→nucleoside→free base, whereas no accumulation of the free base was observed during the hydrolysis of dAMP and dCMP. Copyright (C) 1999 Elsevier Science S.A.
- Chmielowiec, Urszula,Kruszewska, Hanna,Cybulski, Jacek
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p. 611 - 614
(2007/10/03)
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- Development of a 32P-postlabeling method for the detection of 1, N2-propanodeoxyguanosine adducts of 2-hexenal in vivo.
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2-Hexenal is an alpha,beta-unsaturated carbonyl compound which forms cyclic 1,N2-propano adducts in vitro. The adduct formation in vivo was not reported by others to date. Because this type of adduct is considered promutagenic (2-hexenal is actually mutagenic and genotoxic) and humans are permanently exposed to this compound via vegetarian food, 2-hexenal may play a role in carcinogenicity. To improve the cancer risk assessment, we developed a new 32P-postlabeling technique for this compound and optimized the different steps of the postlabeling procedure. The results of the postlabeling methods are shown. A labeling efficiency of 35%, a recovery of 10% for the synthesized standards, and a detection limit of three 2-hexenal adducts per 10(8) nucleotides was achieved. After gavage of 500 mg/kg of body weight to male Fischer 344 rats, the respective DNA adducts were detected in rat liver DNA. With this study, we demonstrate in vivo adduct formation of 2-hexenal for the first time. Highest adduct levels were found 2 days after gavage, and after 4 days, the level was even higher than after 1 day. No adducts were detected 8 h after gavage. The respective adducts could not be found as a background in tissues of untreated rats or in calf thymus DNA at the limit of detection.
- Schuler,Budiawan,Eder
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p. 335 - 340
(2007/10/03)
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- Cleavage of oligodeoxyribonucleotides from polymer supports and their rapid deprotection under microwaves
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Novel conditions for the cleavage of oligodeoxynucleotides from polymer supports and their complete deprotection under microwaves have been developed. The oligonucleotides synthesized using phosphoramidite synthons carrying base labile (Pac, Dmf and t-Bpac) and conventional (Bz for A and C and Pac for G) protecting groups for nucleic bases were deprotected using 0.2M sodium hydroxide (MeOH : H2O :: 1:1, v/v) = Reagent A and 1M sodium hydroxide (MeOH : H2O :: 1:1, v/v) = Reagent B, respectively under microwaves. The deprotected oligonucleotides were found to be comparable with the corresponding oligonucleotides deprotected under standard conditions (aq. ammonia at 55°C).
- Gupta,Kumar
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p. 1761 - 1766
(2007/10/03)
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- Synthesis of sugar-modified 2,6-diaminopurine and guanine nucleosides from guanosine via transformations of 2-aminoadenosine and enzymatic deamination with adenosine deaminase
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Treatment of 2,6-diaminopurine riboside (2-aminoadenosine) with α- acetoxyisobutyryl bromide in acetonitrile gave mixtures of the trans 2',3'- bromohydrin acetates 2. Treatment of 2 with zinc-copper couple effected reductive elimination, and deprotection gave 2,6-diamino-9-(2,3-dideoxy-β- D-erythro-pent-2-enofuranosyl)purine (3a). Treatment of 2 with Dowex 1 x 2 (OH-) resin in methanol gave the 2',3-anhydro derivative 4. Stannyl radical- mediated hydrogenolysis of 2 and deprotection gave the 2'-deoxy 6a and 3'- deoxy 7a nucleosides. Treatment of the 3',5'-O-(tetraisopropyldisiloxanyl) derivative (5a) with trifluoromethanesulfonyl chloride - 4- (dimethylamino)pyridine gave 2'-triflate 5c. Displacement with lithium azide -dimethylformamide and deprotection gave the arabino 2'-azido derivative 8a, which was reduced to give 2,6-diamino-9 (2-amino-2-deoxy-β-D- arabinofuranosyl)purine (8b). Sugar-modified 2,6-diaminopurine nucleosides were treated with adenosine deaminase to give the corresponding guanine analogues. Treatment of 2,6-diaminopurine riboside (2-aminoadenosine) with α-acetoxyisobutyryl bromide in acetonitrile gave mixtures of the trans 2',3'-bromohydrin acetates 2. Treatment of 2 with zinc-copper couple effected reductive elimination, and deprotection gave 2,6-diamino-9-(2,3-dideoxy-β-D-erythro-pent-2-enofuranosyl) purine (3a). Treatment of 2 with Dowex 1 × 2 (OH-) resin in methanol gave the 2',3'-anhydro derivative 4. Stannyl radical-mediated hydrogenolysis of 2 and deprotection gave the 2'-deoxy 6a and 3'-deoxy 7a nucleosides. Treatment of the 3',5'-O-(tetraisopropyldisiloxanyl) derivative (5a) with trifluoromethanesulfonyl chloride - 4-(dimethylamino)pyridine gave 2'-triflate 5c. Displacement with lithium azide - dimethylformamide and deprotection gave the arabino 2'-azido derivative 8a, which was reduced to give 2,6-diamino-9-(2-amino-2-deoxy-β-D-arabinofuranosyl)purine (8b). Sugar-modified 2,6-diaminopurine nucleosides were treated with adenosine deaminase to give the corresponding guanine analogues.
- Robins, Morris J.,Zou, Ruiming,Hansske, Fritz,Wnuk, Stanislaw F.
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p. 762 - 767
(2007/10/03)
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- Hydrolysis of phosphomonoesters in nucleotides by cerium(IV) ions. Highly selective hydrolysis of monoester over diester in concentrated buffers
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Phosphomonoesters in nucleotides are efficiently hydrolysed by CeIV ions under physiological conditions. The half-lives of the residues at pH 7.2 and 50 °C ([CeIV] = 10 mM) are around 10 min. Phosphomonoester hydrolysis by CeIV ions is faster than the hydrolysis of phosphodiesters. Significantly, the selectivity for monoester hydrolysis over diester hydrolysis is remarkably increased by using concentrated buffer solutions (TRIS and HEPES). In 500 mM TRIS buffer, pdA and dAp are hydrolysed 500- and 580-fold faster than is d(ApA), whereas the corresponding ratios in 50 mM TRIS buffer are 85 and 90 respectively. Selective removal of the terminal monophosphate from d(pApA) is achieved by CeIV in these concentrated buffers.
- Miyama, Sachiko,Asanuma, Hiroyuki,Komiyama, Makoto
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p. 1685 - 1688
(2007/10/03)
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