961-07-9Relevant articles and documents
Oxidative conversion of N-dimethylformamidine nucleosides to N-cyano nucleosides
Mullah,Mullah, Bashar,Andrus,Andrus, Alex,Zhao,Zhao, Hong,Jones,Jones, Roger A.
, p. 4373 - 4376 (1995)
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.
Chemical composition and toxicity of Taiwanese betel quid extract
Wang,Su,Lii
, p. 135 - 144 (1999)
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.
Independent Generation and Time-Resolved Detection of 2′-Deoxyguanosin-N2-yl Radicals
Dai, Xiaojuan,Greenberg, Marc M.,Su, Hongmei,Zheng, Liwei
, (2020)
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
Independent Generation and Reactivity of 2′-Deoxyguanosin- N1-yl Radical
Zheng, Liwei,Greenberg, Marc M.
, p. 8665 - 8672 (2020/07/03)
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.
Thermodynamic Reaction Control of Nucleoside Phosphorolysis
Kaspar, Felix,Giessmann, Robert T.,Neubauer, Peter,Wagner, Anke,Gimpel, Matthias
supporting information, p. 867 - 876 (2020/01/24)
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.).
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
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.
, p. 10948 - 10957 (2019/12/23)
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.
Oxidation of 1-N2-etheno-2′-deoxyguanosine by singlet molecular oxygen results in 2′-deoxyguanosine: A pathway to remove exocyclic DNA damage?
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
, p. 859 - 867 (2018/05/04)
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.
Hydrogen peroxide-Triggered gene silencing in mammalian cells through boronated antisense oligonucleotides
Mori, Shohei,Morihiro, Kunihiko,Okuda, Takumi,Kasahara, Yuuya,Obika, Satoshi
, p. 1112 - 1118 (2018/02/09)
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.
Independent Photochemical Generation and Reactivity of Nitrogen-Centered Purine Nucleoside Radicals from Hydrazines
Zheng, Liwei,Lin, Lu,Qu, Ke,Adhikary, Amitava,Sevilla, Michael D.,Greenberg, Marc M.
supporting information, p. 6444 - 6447 (2017/12/08)
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.
PRODUCTION METHOD OF NUCLEOSIDE COMPOUND
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Paragraph 0032-0033, (2017/03/24)
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
