- Preparation of pyrenyl-modified nucleosides via Suzuki-Miyaura cross-coupling reactions
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The modified nucleosides 5-pyrenyl-2′-deoxyuridine (1) and 8-pyrenyl-2′-deoxyguanosine (2) were synthesized via palladium-catalyzed Suzuki-Miyaura cross-coupling reactions of pyren-1-yl boronic acid (3) to either 5-iodo-2′-deoxyuridine (4), or 8-bromo-2′-deoxyguanosine (7), respectively. No protecting groups for the hydroxy and amino functions of the nucleoside are needed during the preparation. Both pyrene derivatives are suitable nucleoside models for the spectrosopic investigation of reductive electron transfer (in 1), or oxidative hole transfer (in 2).
- Amann, Nicole,Wagenknecht, Hans-Achim
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- DNA-polyamine cross-links generated upon one electron oxidation of DNA
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The possibility to induce the formation of covalent cross-links between polyamines and guanine following one electron oxidation of double stranded DNA has been evaluated. For such a purpose, a strategy has been developed to chemically synthesize the polyamine-C8-guanine adducts, and efforts have been made to characterize them. Then, an analytical method, based on HPLC separation coupled through electrospray ionization to tandem mass spectrometry, has been setup for their detection and quantification. Using such a sensitive approach, we have demonstrated that polyamine-C8-guanine adducts could be produced with significant yields in double stranded DNA following a one-electron oxidation reaction induced by photosensitization. These adducts, involving either putrescine, spermine, or spermidine, are generated by the nucleophilic addition of primary amino groups of polyamines onto the C8 position of the guanine radical cation. Our data demonstrate that such a nucleophilic addition of polyamines is much more efficient than the addition of a water molecule that leads to 8-oxo-7,8-dihydroguanine formation.
- Silerme, Stéphanie,Bobyk, Laure,Taverna-Porro, Marisa,Cuier, Camille,Saint-Pierre, Christine,Ravanat, Jean-Luc
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- 8-Substituted guanosine and 2'-deoxyguanosine derivatives as potential inducers of the differentiation of Friend erythroleukemia cells
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A variety of 8-substituted guanosine and 2'-deoxyguanosine derivatives were synthesized and tested as inducers of the differentiation of Friend murine erythroleukemia cells in culture. The most active agents in the guanosine series were 8-substituted -N(CH3)2, -NHCH3, -NH2, -OH, and -SO2CH3, which caused 68, 42, 34, 33, and 30% of erythroleukemia cells to attain benzidine positivity, a functional measure of maturation, at concentrations of 5, 1, 0.4, 5, and 5 mM, respectively. The 8-OH derivative of the 2'-deoxyguanosine series produced comparable activity, causing 62% benzidine-positive cells at a level of 0.2 mM. These findings indicate that 8-substituted analogues of guanosine and 2'-deoxyguanosine have the potential to terminate leukemia cell proliferation through conversion to end-stage differentiated cells.
- Lin,Cheng,Ishiguro,Sartorelli
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- An improved synthesis of 8-bromo-2'-deoxyguanosine
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A new synthesis of 8-bromo-2'-deoxyguanosine, a key intermediate in the synthesis of the mutagenic DNA adduct 8-oxo-2'-deoxyguanosine is described. The advantage of this method are significantly improved yields and ease of isolation.
- Gannett,Sura
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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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- Synthesis and optical properties of the C-8 adduct of benzo[a]pyrene and deoxyguanosine
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8-(Benzo[a]pyren-6-yl)-2′-deoxyguanosine (Bp-dG) was prepared via a palladium-catalyzed Suzuki-Miyaura-type cross-coupling reaction from the pinacol ester of 6-benzo[a]pyrenyl boronic acid and the corresponding brominated deoxyguanosine precursor. The absorption and steady-state fluorescence properties of Bp-dG were characterized and compared with that of 6-benzo[a]pyrene. The modified nucleoside Bp-dG exhibits an unexpected high stability towards nucleosidic hydrolysis even under irradiation with UV light. Georg Thieme Verlag Stuttgart.
- Valis, Linda,Wagenknecht, Hans-Achim
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- Synthesis of oligonucleotides bearing an arylamine modification in the C8-position of 2′-deoxyguanosine
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C8-Arylamine-dG adducts were converted into their corresponding 5′-0-DMTr-3′-0-phosphoramidite-C8-arylamine-dG derivatives. These compounds were used for the automated synthesis of site-specifically modified oligonucleotides. The oligonucleotides were stu
- Meier,Graesl,Detmer,Marx
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- Expanding the hoogsteen edge of 2′-deoxyguanosine: Consequences for G-quadruplex formation
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(Chemical Equation Presented) The synthesis and self-assembling properties of 8-aryl-2′-deoxyguanosine derivatives are described. Our studies suggest that a properly placed acetyl group can increase the stability and specificity of the resulting G-quadrup
- Gubala, Vladimir,Betancourt, Jose E.,Rivera, Jose M.
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- An indole-linked C8-deoxyguanosine nucleoside acts as a fluorescent reporter of Watson-Crick versus Hoogsteen base pairing
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Pyrrole- and indole-linked C8-deoxyguanosine nucleosides act as fluorescent reporters of H-bonding specificity. Their fluorescence is quenched upon Watson-Crick H-bonding to dC, while Hoogsteen H-bonding to G enhances emission intensity. The indole-linked probe is ~ 10-fold brighter and shows promise as a fluorescent reporter of Hoogsteen base pairing. The Royal Society of Chemistry 2011.
- Schlitt, Katherine M.,Millen, Andrea L.,Wetmore, Stacey D.,Manderville, Richard A.
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- Synthesis of 8-oxo-dGTP and its β,γ-CH2-, β,γ-CHF-, and β,γ-CF2- analogues
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Three novel bisphosphonate analogues of 8-oxo-dGTP 3 in which the bridging β,γ-oxygen is replaced by a methylene, fluoromethylene or difluoromethylene group (4–6, respectively) have been synthesized from 8-oxo-dGMP 2 by reaction of its morpholine 5′-phosphoramidate 14 or preferably, its N-methylimidazole 5′-phosphoramidate 15 with tri-n-butylammonium salts of the appropriate bisphosphonic acids, 11–13. The latter method also provides a convenient new route to 3. Analogues 4–6 may be useful as mechanistic probes for the role of 3 in abnormal DNA replication and repair.
- Zheng, Yiying,Haratipour, Pouya,Kashemirov, Boris A.,McKenna, Charles E.
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supporting information
(2021/02/22)
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- Synthesis of Phosphoramidite Monomers Equipped with Complementary Bases for Solid-Phase DNA Oligomerization
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We describe the preparation of two monomers that bear complementary nucleobases at the edges (guanine-2′-deoxycytidine and 2-aminoadenine-2′-deoxyuridine) and that are conveniently protected and activated for solid-phase automated DNA synthesis. We report the optimized synthetic routes leading to the four nucleobase derivatives involved, their cross-coupling reactions into dinucleobase-containing monomers, and their oligomerization in the DNA synthesizer.
- Romero-Pérez, Sonia,López-Martín, Isabel,Martos-Maldonado, Manuel C.,Somoza, álvaro,González-Rodríguez, David
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supporting information
p. 41 - 45
(2020/01/03)
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- Tracking the formation of supramolecular G-quadruplexes via self-assembly enhanced emission
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We report the synthesis and self-assembly of two lipophilic 2′-deoxyguanosine (G) derivatives whose fluorescence intensity is modulated by self-assembly into supramolecular G-quadruplexes (SGQs). Whereas both derivatives self-assemble isostructurally, one shows up to 100% emission enhancement while the other shows an initial enhancement, followed by 10% quenching. Thus, the rotational restrictions resulting from self-assembly are enough to induce significant changes in emission, but it is critical to consider the specific interactions between fluorophores since they will determine the ultimate emission signature. These findings could open the door to the development of luminescent supramolecular sensors and probes.
- Silva-Brenes, Diana,Delgado, Loruhama,Rivera, José M.
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supporting information
p. 782 - 786
(2017/02/05)
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- Tracking Hole Transport in DNA Hairpins Using a Phenylethynylguanine Nucleobase
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The hole transport dynamics of DNA hairpins possessing a stilbene electron acceptor and donor along with a modified guanine (G) nucleobase, specifically 8-(4′-phenylethynyl)deoxyguanosine, or EG, have been investigated. The nearly indistinguishable oxidation potentials of EG and G and unique spectroscopic characteristics of EG+? make it well-suited for directly observing transient hole occupation during charge transport between a stilbene electron donor and acceptor. In contrast to the cation radical G+?, EG+? possesses a strong absorption near 460 nm and has a distinct Raman-active ethynyl stretch. Both spectroscopic characteristics are easily distinguished from those of the stilbene donor/acceptor radical ion chromophores. Employing EG, we observe its role as a shallow hole trap, or as an intermediate hole transport site when a deeper trap state is present. Using a combination of ultrafast absorption and stimulated Raman spectroscopies, the hole-transport dynamics are observed to be similar in systems having EG vs G bases, with small perturbations to the charge transport rates and yields. These results show EG can be deployed at specified locations throughout the sequence to report on hole occupancy, thereby enabling detailed monitoring of the hole transport dynamics with base-site specificity.
- Brown, Kristen E.,Singh, Arunoday P. N.,Wu, Yi-Lin,Mishra, Ashutosh Kumar,Zhou, Jiawang,Lewis, Frederick D.,Young, Ryan M.,Wasielewski, Michael R.
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supporting information
p. 12084 - 12092
(2017/09/07)
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- Guanosine-based hydrogen-bonded 2D scaffolds: Metal-free formation of G-quartet and G-ribbon architectures at the solid/liquid interface
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We report on the synthesis and self-assembly of three novel lipophilic guanosine derivatives exposing a ferrocene moiety in the C(5′) position of the sugar unit. Their self-association in solution, and at the solid/liquid interface, can be tuned by varying the size and nature of the C(8)-substituent, leading to the generation of either G-ribbons, lamellar G-dimer based arrays or the G4 cation-free architectures.
- Garah, Mohamed El,Perone, Rosaria C.,Bonilla, Alejandro Santana,Haar, Sébastien,Campitiello, Marilena,Gutierrez, Rafael,Cuniberti, Gianaurelio,Masiero, Stefano,Ciesielski, Artur,Samorì, Paolo
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supporting information
p. 11677 - 11680
(2015/07/15)
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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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- Enzymatic synthesis of 8-vinyl- and 8-styryl-2′-deoxyguanosine modified DNA - Novel fluorescent molecular probes
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Fluorescent analogs of the natural nucleobases are widely used as molecular probes for investigating DNA hybridization and topology. In this study the guanosine analogs 8-vinyl- and 8-styryl-2′-deoxyguanosine were synthesized and converted into the corres
- Holzberger, Bastian,Strohmeier, Julian,Siegmund, Vanessa,Diederichsen, Ulf,Marx, Andreas
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supporting information; experimental part
p. 3136 - 3139
(2012/06/17)
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- COMPOUNDS FOR TREATING BACTERIAL INFECTIONS
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The present invention generally relates to Rel proteins as a novel therapeutic target for treating bacterial threats. More specifically, the present invention relates to a novel class of compounds of formula (I) which inhibit RelA and/or Relseq and/or Rel
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Page/Page column 36
(2012/02/15)
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- C8-heteroaryl-2′-deoxyguanosine adducts as conformational fluorescent probes in the narl recognition sequence
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The optical, redox, and electronic properties of C8-heteroaryl- 2′-deoxyguanosine (dG) adducts with C8-substituents consisting of furyl (FurdG), pyrrolyl (PyrdG), thienyl ( ThdG), benzofuryl (Bfu
- Rankin, Katherine M.,Sproviero, Michael,Rankin, Keegan,Sharma, Purshotam,Wetmore, Stacey D.,Manderville, Richard A.
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p. 10498 - 10508
(2013/02/25)
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- Discovery and synthesis of New UV-induced intrastrand C(4-8)G and G(8-4)C photolesions
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UV irradiation of cellular DNA leads to the formation of a number of defined mutagenic DNA lesions. Here we report the discovery of new intrastrand C(4-8)G and G(8-4)C cross-link lesions in which the C(4) amino group of the cytosine base is covalently lin
- Muenzel, Martin,Szeibert, Claudia,Glas, Andreas F.,Globisch, Daniel,Carell, Thomas
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supporting information; experimental part
p. 5186 - 5189
(2011/06/17)
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- Synthesis of N 2-Alkyl-8-oxo-7,8-dihydro-2′-deoxyguanosine derivatives and effects of these modifications on RNA duplex stability
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N2-Alkyl analogues of 8-oxo-7,8-dihydro-2′-deoxyguanosine (OG) were synthesized (alkyl = propyl, benzyl) via reductive amination of the protected OG nucleoside and incorporated into various positions of an RNA strand. Thermal stability studies of duplexes containing A or C opposite a single modified base revealed only moderate destabilization. Both OG as well as its N2-alkyl analogues can pair opposite A or C with nearly equal stability, potentially offering a new means of modulating RNA-protein interactions in the minor vs major grooves.
- Kannan, Arunkumar,Burrows, Cynthia J.
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supporting information; experimental part
p. 720 - 723
(2011/03/20)
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- Fluorescent properties and conformational preferences of C-linked phenolic-DNA adducts
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Phenolic toxins and mutagenic diazoquinones generate C-linked adducts at the C8 site of 2′-deoxyguanosine (dG) through the intermediacy of radical species. We have previously reported the site-specific incorporation of these adducts into oligonucleotides
- Omumi, Alireza,Millen, Andrea L.,Wetmore, Stacey D.,Manderville, Richard A.
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experimental part
p. 1694 - 1709
(2012/04/23)
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- Cation-mediated energy transfer in G-quadruplexes revealed by an internal fluorescent probe
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A single pyridine unit incorporated into G-quadruplex DNA has revealed efficient energy transfer reactions in cation-containing G-quadruplexes. 8-(2-Pyridyl)-2′-deoxyguanosine, "2PyG", is a highly sensitive internal fluorescent probe of G-quadruplex folding and energy transfer. 2PyG was minimally disruptive to G-quadruplex folding and exhibited intense fluorescence, even when it was base-stacked with other guanine residues. Using 2PyG we have quantified energy transfer efficiencies within G-quadruplex structures prepared under conditions of excess Na+/K+ (110 mM) or in 40% polyethylene glycol (PEG) under salt deficient conditions. G-quadruplex structures containing coordinated cations exhibited efficient DNA-to-probe energy transfer reactions (ηt = 0.11-0.41), while PEG-folded G-quadruplexes exhibited very little energy transfer (ηt = 0.02-0.07). Experiments conducted using unmodified G-quadruplexes suggest that cation coordination at the O6 position of guanine residues results in enhanced quantum yields of G-quadruplex nucleobases that, in turn, serve as efficient energy donors to 2PyG. Given the growing interest in G-quadruplex-based devices and materials, these results will provide important design principles toward harnessing the potentially useful photophysical properties of G-quadruplex wires and other G-rich structures.
- Dumas, Anaelle,Luedtke, Nathan W.
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supporting information; experimental part
p. 18004 - 18007
(2011/02/26)
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- Triggering of guanosine self-assembly by light
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Chemical Representation Light switches: The introduction of a photoactive moiety into a lipophilic guanosine derivative allows photocontrol over the self-assembly of the molecule. The existence of C-quartets can be alternately switched on and off (see pic
- Lena, Stefano,Neviani, Paolo,Masiero, Stefano,Pieraccini, Silvia,Spada, Gian Piero
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scheme or table
p. 3657 - 3660
(2010/08/19)
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- Chemical and immunochemical detection of 8-halogenated deoxyguanosines at early stage inflammation
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Myeloperoxidase (MPO) generates reactive halogenating species that can modify DNA. The aim of this study was to investigate the formation of 8-halogenated 2′-deoxyguanosines (8-halo-dGs) during inflammatory events. 8-Bromo-2′-dG (8-BrdG) and 8-chloro-2′-dG (8-CldG) were generated by treatment of MPO with hydrogen peroxide at physiological concentrations of Cl- and Br-. The formation of 8-halo-dGs with other oxidative stress biomarkers in lipopolysaccharide-treated rats was assessed by liquid chromatography tandem mass spectrometry and immunohistochemistry using a novel monoclonal antibody (mAb8B3) to 8-BrdG-conjugated keyhole limpet hemocyanin. The antibody recognized both 8-BrdG and 8-CldG. In the liver of lipopolysaccharide-treated rats, immunostaining for 8-halodGs, halogenated tyrosines, and MPO were increased at 8 h, whereas those of 8-oxo-2′-dG (8-OxodG) and 3-nitrotyrosine were increased at 24 h. Urinary excretion of both 8-CldG and 8-BrdG was also observed earlier than those of 8-OxodG and modified tyrosines (3-nitrotyrosine, 3-chlorotyrosine, and 3-bromotyrosine). Moreover, the levels of the 8-halo-dGs in urine from human diabetic patients were 8-fold higher than in healthy subjects (n = 10, healthy and diabetic, p 0.0001), whereas there was a moderate difference in 8-OxodG between the two groups (p 0.001). Interestingly, positive mAb8B3 antibody staining was observed in liver tissue from hepatocellular carcinoma patients but not in liver tissue from human cirrhosis patients. These data suggest that 8-halo-dGs may be potential biomarkers of early inflammation.
- Asahi, Takashi,Kondo, Hajime,Masuda, Mitsuharu,Nishino, Hoyoku,Aratani, Yasuaki,Naito, Yuji,Yoshikawa, Toshikazu,Hisaka, Shinsuke,Kato, Yoji,Osawa, Toshihiko
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experimental part
p. 9282 - 9291
(2011/03/18)
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- Synthesis of oligonucleotides containing 2′-deoxyguanosine adducts of nitropyrenes
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Two different approaches to synthesize oligonucleotides containing the 2′-deoxyguanosine adducts formed by nitropyrenes are described. A direct reaction of an unmodified oligonucleotide with an activated nitropyrene derivative is a convenient biomimetic approach for generating the major adducts in DNA. A total synthetic approach, by contrast, involves several synthetic steps, including Buchwald-Hartwig Pd-catalyzed coupling, but can be used for incorporating both the major and minor adducts in DNA in high yield. Copyright Taylor & Francis Group, LLC.
- Colis, Laureen C.,Chakraborti, Debasis,Hilario, Pablo,McCarty, Christopher,Basu, Ashis K.
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scheme or table
p. 67 - 77
(2009/05/30)
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- Synthesis of DNA-oligonucleotides damaged by arylamine-modified 2′-deoxyguanosine
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C8-Arylamine-dG adducts bearing a labile N-formamidine group at the exocyclic amino function were converted into their corresponding 5′-O-DMTr-3′-O-phosphoramidite-C8-arylamine-dG derivatives. These compounds were used for the automated synthesis of site-
- Boege,Szombati,Meier
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p. 705 - 708
(2008/09/17)
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- Fluorometric sensing of the salt-induced B-Z DNA transition by combination of two pyrene-labeled nucleobases
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We have developed a new fluorescent DNA sensor containing two pyrene-labeled nucleobases, PetG and PyC, and the fluorescence color was altered by the salt-induced B-Z DNA transtion. The Royal Society of Chemistry 2005.
- Okamoto, Akimitsu,Ochi, Yuji,Saito, Isao
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p. 1128 - 1130
(2007/10/03)
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- Preparation of C8-amine and acetylamine adducts of 2′-deoxyguanosine suitably protected for DNA synthesis
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(Equation presented) C8-Amine and acetylamine adducts of 2′-deoxyguanosine were synthesized. Our approach provides solutions for the coupling of aromatic amines to a protected 8-bromo-2′-deoxyguanosine derivative, for the selective acetylation of the coup
- Gillet, Ludovic C. J.,Schaerer, Orlando D.
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p. 4205 - 4208
(2007/10/03)
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- Highly efficient synthesis of a phosphoramidite building block of C8-deoxyguanosine adducts of aromatic amines
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The synthesis of 5′-O-DMTr-3′-O-phosphoramidite-C8-arylamine-dG adducts 11 and 12 is described. The compounds are potential building blocks for the automated synthesis of site-specifically modified oligonucleotides. The C8-adducts were synthesized by a pa
- Meier, Chris,Gra?sl, Sonja
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p. 802 - 804
(2007/10/03)
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- Methods of screening for nucleoside analogs that are incorporated by HIV reverse transcriptase and cause incorrect base pairing
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Methods and compositions related to HIV are disclosed. Using the methods of the present invention, nucleoside analogs may be screened for the ability to be incorporated by reverse transcriptase of human immunodeficiency virus ("HIV RT") and cause incorrec
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- Synthesis of 8-oxo-7,8-dihydro-6-O-methyl-2′-deoxyguanosine and its use as a probe to study DNA-base excision by mutY enzyme
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A 23mer oligomer containing 8-oxo-7,8-dihydro-6-O-methyl-2′-deoxyguanosine (1) has been synthesized from 2′-deoxyguanosine. The activity of MutY protein toward this and a related oligomer containing 8-methoxy-dG has been studied.
- Varaprasad, Chamakura V.,Bulychev, Nickolai,Grollman, Arthur P.,Johnson, Francis
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