- Simple method for fast deprotection of nucleosides by triethylamine- catalyzed methanolysis of acetates in aqueous medium
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A straightforward methodology for deacetylation of protected ribonucleosides was developed based on triethylamine-catalyzed solvolysis in aqueous methanol. Reactions are completed in a few minutes under microwave irradiation and the free nucleosides are obtained in high yield after simple evaporation of volatiles. Other important features include the involvement of readily available reagents and the compatibility with diverse functional groups, which make this process very attractive for broad application.
- Meier, Lidiane,Monteiro, Gustavo C.,Baldissera, Rodrigo A.M.,Sa?, Marcus Mandolesi
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- Heterocyclic Synthesis via a 1,3-Dicyclohexylcarbodiimide-Mediated Cyclodesulfurative Annulation Reaction. New Methodology for the Preparation of Guanosine and Guanosine-Type Nucleoside Analogues
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Treatment of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide (1, AICA-ribonucleoside) with methoxycarbonyl isothiocyanate followed by cyclodesulfurization of the resulting methoxycarbonylated thioureido derivative with 1,3-dicyclohexylcarbodiimide (DCC) has furnished 5--1-β-D-ribofuranosylimidazole-4-carbonitrile (6), not 2--9-β-D-ribofuranosylpurin-6-one (4).Using 1 labeled with 18O in the carboxamide moiety, the conversion of 1 to 6 is shown to proceed with retention of the 18O label.This finding has suggested the presence of a oxazine intermediate in an intramolecular dehydration reaction mechanism.Under similar reaction conditions, methyl 5-amino-1-β-D-ribofuranosylimidazole-4-carboximidate (13) affords 6-methoxy-2--9-β-D-ribofuranosylpurine (14), which gives guanosine upon deprotection with iodotrimethylsilane.The use of this methoxycarbonyl isothiocyanate/DCC cyclodesulfurization method on heterocyclic o-amino carboximidate esters thus provides a highly efficient entry into the class of guanosine-type nucleoside analogues.
- Groziak, Michael P.,Chern, Ji-Wang,Townsend, Leroy B.
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- N,N-Dibenzyl formamidine as a new protective group for primary amines
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Primary amines can be converted in high yield into N,N-dibenzyl formamidines under mild conditions. The N,N-dibenzyl formamidine group was found to be effective as a protective group for primary amines as it is stable to a variety of conditions and can be removed by catalytic hydrogenation.
- Vincent, Stephane,Mons, Stephane,Lebeau, Luc,Mioskowski, Charles
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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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- THE PROTECTION OF 2'-HYDROXY FUNCTIONS IN OLIGORIBONUCLEOTIDE SYNTHESIS
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The suitability of the 4-methoxytetrahydropyran-4-yl group for the protection of 2' ( or 3')-hydroxy functions in oligoribonucleotide synthesis is confirmed; the latter protecting group is removed in 0.01M-hydrochloric acid at room temperature under conditions which, contrary to a recent report, lead to no detectable cleavage or migration of the internucleotide phosphodiester linkages.
- Norman, G. David,Reese, B. Colin,Serafinowska, T. Halina
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- Chemical radiation studies of 8-bromoguanosine in aqueous solutions
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Chemical radiolytic methods were used to investigate the reactions of hydrated electrons (eaq-) with 8-bromoguanosine (8-Br-Guo) as a function of pH. γ-Radiolysis of 8-Br-Guo in aqueous solutions followed by product studies showed the formation of guanosine (Guo) as a single product at various pH. In D2O solutions the quantitative incorporation of deuterium at the 8-position was also observed. Pulse radiolysis revealed the instantaneous formation of a guanosine radical cation (Guo.+ or its deprotonated forms) in acid or basic solutions. The same transient species results from the reaction of H. with 8-Br-Guo at pH 3, as well as from the reaction of (CH3)2CO.- with 8-Br-Guo at pH 13. In neutral solution, the initial electron adduct was rapidly protonated to give the first observable transient species that decays by first-order kinetics (k = 5 × 104 s-1) to produce the Guo(-H+). radical once again. Tailored experiments allowed the reaction mechanism to be defined in some detail.
- Ioele, Marcella,Bazzanini, Rita,Chatgilialoglu, Chryssostomos,Mulazzani, Quinto G.
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- Hydrolytic reactions of guanosyl-(3′,3′)-uridine and guanosyl-(3′,3′)-(2′,5′-di-O-methyluridine)
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Hydrolytic reactions of guanosyl-(3′,3′)-uridine and guanosyl-(3′,3′)-(2′,5′-di-O-methyluridine) have been followed by RP HPLC over a wide pH range at 363.2 K in order to elucidate the role of the 2′-hydroxyl group as a hydrogen-bond donor upon departure of the 3′-uridine moiety. Under neutral and basic conditions, guanosyl-(3′,3′)-uridine undergoes hydroxide ion-catalyzed cleavage (first order in [OH-]) of the P-O3′ bonds, giving uridine and guanosine 2′,3′-cyclic monophosphates, which are subsequently hydrolyzed to a mixture of 2′- and 3′-monophosphates. This bond rupture is 23 times as fast as the corresponding cleavage of the P-O3′ bond of guanosyl-(3′,3′)-(2,5′-di-O-methyluridine) to yield 2′,5′-O-dimethyluridine and guanosine 2′,3′-cyclic phosphate. Under acidic conditions, where the reactivity differences are smaller, depurination and isomerization compete with the cleavage. The effect of Zn2+ on the cleavage of the P-O3′ bonds of guanosyl-(3′,3′)-uridine is modest: about 6-fold acceleration was observed at [Zn2+] = 5 mmol L-1 and pH 5.6. With guanosyl-(3′,3′)-(2′,5′-di-O-methyluridine) the rate-acceleration effect is greater: a 37-fold acceleration was observed. The mechanisms of the partial reactions, in particular the effects of the 2′-hydroxyl group on the departure of the 3′-linked nucleoside, are discussed.
- Kiviniemi, Anu,Loennberg, Tuomas,Ora, Mikko
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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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- Kiteplatin: Differential binding between GSH and GMP
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Glutathione (GSH) plays an important role in the development of resistance to platinum-based chemotherapy, since it can prevent drug binding to DNA and resulting apoptosis of tumor cells. The recently re-discovered drug candidate kiteplatin was found active toward cisplatin- and oxaliplatin-resistant tumor cells, and this could be related to a different interplay of drug-inactivation/DNA-interaction processes. In this study GSH and GMP have been chosen as simple models of platinophiles and DNA, respectively, and the reactivity of kiteplatin has been tested toward GMP, after previous interaction with GSH; toward GSH, after previous interaction with GMP; and toward GMP and GSH simultaneously.
- Petruzzella, Emanuele,Curci, Alessandra,Margiotta, Nicola,Natile, Giovanni,Hoeschele, James D.
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- 1,1,1,3,3,3-Hexafluoro-2-propanol for the Removal of the 4,4'-Dimethoxytrityl Protecting Group from the 5'-Hydroxyl of Acid-Sensitive Nucleosides and Nucleotides
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1,1,1,3,3,3-Hexafluoro-2-propanol is introduced as a suitable reagent and solvent for the detritylation of 5'-O-(4,4'-dimethoxytrityl)-nucleosides and -deoxy- nucleosides, especially those that are susceptible to N-glycosyl cleavage under more strongly acidic conditions.
- Leonard, Nelson J.,Neelima
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- An RNA modification with remarkable resistance to RNase A
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A 3′-deoxy-3′-C-methylenephosphonate modified diribonucleotide is highly resistant to degradation by spleen phosphodiesterase and not cleaved at all by snake venom phosphodiesterase. The most remarkable finding is that, despite the fact that both the vicinal 2-hydroxy nucleophile and the 5′-oxyanion leaving group are intact, the 3′-methylenephosponate RNA modification is also highly resistant towards the action of RNase A.
- Ghidini, Alice,Ander, Charlotte,Winqvist, Anna,Stroemberg, Roger
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- Synthesis of 2'-O-methoxyethylguanosine using a novel silicon-based protecting group.
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A short and efficient synthesis of 2'-O-methoxyethylguanosine (8) is described. Central to this strategy is the development of a novel silicon-based protecting group (MDPSCl(2), 2) used to protect the 3',5'-hydroxyl groups of the ribose. Silylation of guanosine with 2 proceeded with excellent regioselectivity and in 79% yield. Alkylation of the 2'-hydroxyl group of 6 proceeded with methoxyethyl bromide and NaHMDS and afforded compound 7 in 85% yield, without any noticeable cleavage of the silyl protecting group and without the need to protect the guanine base moiety. Finally, deprotection of 7 was achieved using TBAF and produced 8 in 97% yield.
- Wen,Chow, Suetying,Sanghvi, Yogesh S,Theodorakis, Emmanuel A
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- Kinetic analysis of the cleavage of the ribose phosphodiester bond within guanine and cytosine-rich oligonucleotides and dinucleotides at 65-200 °C and its implications concerning the chemical evolution of RNA
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A monitoring method of rapid hydrothermal reactions was successfully applied to a kinetic analysis of the cleavage of a ribose phosphodiester bond within oligonucleotides and dinucleotides at 150-200 °C. The apparent rate constants (kapp) of degradation of the ribose 3′,5′-cytidylylguanosine sequence (-C3′pGd-) within oligonucleotides and dinucleotides were determined, where the -C3′pGd- sequence in oligonucleotides is less stable than 2′,5′-cytidylylguanosine (C2′pG) and 3′,5′-cytidylylguanosine (C3′pG). It was unexpected that the stability of the target sequence would be dependent on the surrounding sequences of the oligonucleotides, although the temperatures used in the study were extremely higher than the melting points. The stability of a phosphodiester bond of 2′-deoxycytidylyl-2′-deoxyguanosine (CdpGd) is much higher than that of a ribose phosphodiester bond at low temperatures, but becomes comparable at 200 °C. During the degradation of C2′pG or C3′pG, interconversion between C2′pG and C3′pG was observed along with cleavage of the phosphodiester bond. Based on an analysis of the extent of interconversion, the apparent rate constants of the disappearance of C2′pG and C3′pG were dissected into the rate constants of hydrolysis (khy) and interconversion (kint), where the values of khy were greater than those of kint. The apparent activation energy of the degradation of the target sequence was 100-109 kJ mol-1 for oligonucleotides, 90 kJ mol-1 for C3′pG, and 87 kJ mol-1 for C2′pG, and 139 kJ mol-1 for CdpGd. The apparent activation enthalpy and entropy changes of the degradation of the target sequence were also determined; the values of the activation parameter were ΔHapp = 94-105 kJ mol-1 and ΔSapp= -(36-59) J mol-1 T-1 for five oligonucleotides, ΔHapp = 86 kJ mol-1 and ΔSapp = -97 J mol-1 T-1 for C3′pG, ΔHapp = 84 kJ mol-1, ΔXSapp = - 105 J mol-1 T-1 for C2′pG, and ΔHapp = 135 kJ mol-1, ΔSapp = +2 J mol-1 T-1 for CdpGd. The activation parameters, ΔHapp and ΔSapp, for the oligonucleotides increased with the length of the surrounding sequence of -C3′pGd-; this fact clearly demonstrates the existence of the influence of the surrounding sequence for the stability of the target ribose phosphodiester bond. Based on a kinetic analysis, the reaction mechanism of the degradation of the ribose phosphodiester bond at high temperatures is discussed. Furthermore, possible pathways of the chemical evolution of RNA are discussed from the viewpoint of the hydrothermal origin of life.
- Kawamura, Kunio
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- An efficient approach for conversion of 5-substituted 2-thiouridines built in RNA oligomers into corresponding desulfured 4-pyrimidinone products
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Abstract An efficient approach for the desulfuration of C5-substituted 2-thiouridines (R5S2U) bound in the RNA chain exclusively to 4-pyrimidinone nucleoside (R5H2U)-containing RNA products is proposed. This post-synthetic transformation avoids the preparation of a suitably protected H2U phosphoramidite, which otherwise would be necessary for solid-phase synthesis of the modified RNA. Optimization of the desulfuration, which included reaction stoichiometry, time and temperature, allowed to transform a set of ten R5S2U-RNAs into their R5H2U-RNA congeners in ca. 90% yield.
- Chwialkowska, Anna,Wielgus, Ewelina,Leszczynska, Grazyna,Sobczak, Milena,Mikolajczyk, Barbara,Sochacka, Elzbieta,Nawrot, Barbara
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- Oxidation of 8-thioguanosine gives redox-responsive hydrogels and reveals intermediates in a desulfurization pathway
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A disulfide made by oxidation of 8-thioguanosine is a supergelator. The hydrogels are redox-responsive, as they disassemble upon either reduction or oxidation of the S-S bond. We also identified this disulfide, and 2 other compounds, as intermediates in oxidative desulfurization of 8-thioG to guanosine. This journal is
- Chen, Fu,Davis, Jeffery T.,Gutierrez, Osvaldo,Lee, Wes,Xiao, Songjun,Zavalij, Peter Y.
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- Watson-Crick Base Pairing between Guanosine and Cytidine Studied by 13C Nuclear Magnetic Resonance Spectroscopy
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Watson-Crick base pairing in dimethyl sulfoxide/methanol (2/1 v/v) between the nucleosides guanosine and cytidine has been studied by carbon -13 nuclear magnetic resonance (13C NMR) spectroscopy at 67.89 MHz.The equilibrium constant for the base pairing complex has been obtained at two different temperatures by a nonlinear least-squares analysis of the experimental shift data for the base carbons, and the enthalpy of interaction has been found to be ca. -3.8 kcal/mol.The analysis furthermore indicates that while base pairing and changes in the syn/anti conformation ratio are independent processes in the case of guanosine, a change from syn to anti conformation occurs simultaneously with the base pairing in the case of cytidine, in agreement with the Watson-Crick base pairing model.As inferred from the results base pairing alters the polarizabilities of the nucleosides.
- Petersen, Steffen B.,Led, Jens J.
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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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- Biocatalytic separation of N -7/ N -9 guanine nucleosides
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Vorbrueggen coupling of trimethylsilylated 2-N-isobutanoylguanine with peracetylated pentofuranose derivatives generally gives inseparable N-7/N-9 glycosyl mixtures. We have shown that the two isomers can be separated biocatalytically by Novozyme-435-mediated selective deacetylation of the 5′-O-acetyl group of peracetylated N-9 guanine nucleosides.
- Singh, Sunil K.,Sharma, Vivek K.,Olsen, Carl E.,Wengel, Jesper,Parmar, Virinder S.,Prasad, Ashok K.
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- Lanthanide-mediated phosphoester hydrolysis and phosphate elimination from phosphopeptides
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Lanthanide ions can mediate both phosphomonoester hydrolysis and β-elimination of inorganic phosphate from polypeptide substrates under near-physiological conditions of ph, temperature, and salt. The Royal Society of Chemistry 2005.
- Luedtke, Nathan W.,Schepartz, Alanna
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- Converging fate of the oxidation and reduction of 8-thioguanosine
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Thione-containing nucleobases have attracted the attention of the scientific community for their application in oncology, virology, and transplantology. The detailed understanding of the reactivity of the purine derivative 8-thioguanosine (8-TG) with reactive oxygen species (ROS) and free radicals is crucial for its biological relevance. An extensive investigation on the fate of 8-TG under both reductive and oxidative conditions is here reported, and it was tested by employing steady-state photooxidation, laser flash photolysis, as well as γ-radiolysis in aqueous solutions. The characterization of the 8-TG T1 excited state by laser flash photolysis and the photooxidation experiments confirmed that singlet oxygen is a crucial intermediate in the formation of the unexpected reduced product guanosine, without the formation of the usual oxygenated sulfinic or sulfonic acids. Furthermore, a thorough screening of different radiolytic conditions upon γ-radiation afforded the reduced product. These results were rationalized by performing control experiments in the predominant presence of each reactive species formed by radiolysis of water, and the mechanistic pathway scenario was postulated on these bases.
- Taras-Goslinska, Katarzyna,Vetica, Fabrizio,Barata-Vallejo, Sebastián,Triantakostanti, Virginia,Marciniak, Bronis?aw,Chatgilialoglu, Chryssostomos
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- Dissociation of Platinum(II) Nucleobase Complexes - Evidence for a Three-path Mechanism via a Five-coordinate Intermediate
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In thiourea assisted dissociation of 2+ (Guo = guanosine, dien = diethylenetriamine) in aqueous solution (pH = ca. 3) the nucleophile dependent reaction follows a three-path mechanism, in which the initial binding of the nucleophile to the complex and the ring-opening step of the terdentate dien ligand are reversible.
- Mikola, Marjaana,Vihanto, Jouko,Arpalahti, Jorma
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- STRUCTURE OF A NEW MODIFIED NUCLEOSIDE FORMED BY GUANOSINE-MALONALDEHYDE REACTION
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A new modified nucleoside was formed by the reaction of guanosine with malonaldehyde under acidic condition.This compound emitted strong yellow fluorescence and was hydrolyzed by NaOH into guanosine and malonaldehyde.Its structure was determined to be 1,N2-(1-propenyl-3-ylidene)guanosine by the spectroscopic analysis.
- Seto, Hiroshi,Akiyama, Kazuyuki,Okuda, Taisuke,Hashimoto, Tsuyoshi,Takesue, Tomoyuki,Ikemura, Tadashi
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- Vinyluridine as a Versatile Chemoselective Handle for the Post-transcriptional Chemical Functionalization of RNA
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The development of modular and efficient methods to functionalize RNA with biophysical probes is very important in advancing the understanding of the structural and functional relevance of RNA in various cellular events. Herein, we demonstrate a two-step bioorthogonal chemical functionalization approach for the conjugation of multiple probes onto RNA transcripts using a 5-vinyl-modified uridine nucleotide analog (VUTP). VUTP, containing a structurally noninvasive and versatile chemoselective handle, was efficiently incorporated into RNA transcripts by in vitro transcription reactions. Furthermore, we show for the first time the use of a palladium-mediated oxidative Heck reaction in functionalizing RNA with fluorogenic probes by reacting vinyl-labeled RNA transcripts with appropriate boronic acid substrates. The vinyl label also permitted the post-transcriptional functionalization of RNA by a reagent-free inverse electron demand Diels-Alder (IEDDA) reaction in the presence of tetrazine substrates. Collectively, our results demonstrate that the incorporation of VUTP provides newer possibilities for the modular functionalization of RNA with variety of reporters.
- George, Jerrin Thomas,Srivatsan, Seergazhi G.
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- Kinetic properties of Cellulomonas sp. purine nucleoside phosphorylase with typical and non-typical substrates: Implications for the reaction mechanism
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Phosphorolysis catalyzed by Cellulomonas sp. PNP with typical nucleoside substrate, inosine (Ino), and non-typical 7-methylguanosine (m7Guo), with either nucleoside or phosphate (Pi) as the varied substrate, kinetics of the reverse synthetic reaction with guanine (Gua) and ribose-1-phosphate (R1P) as the varied substrates, and product inhibition patterns of synthetic and phosphorolytic reaction pathways were studied by steady-state kinetic methods. It is concluded that, like for mammalian trimeric PNP, complex kinetic characteristics observed for Cellulomonas enzyme results from simultaneous occurrence of three phenomena. These are sequential but random, not ordered binding of substrates, tight binding of me substrate purine bases, leading to the circumstances that for such substrates (products) rapid-equilibrium assumptions do not hold, and a dual role of Pi, a substrate, and also a reaction modifier that helps to release a tightly bound purine base. Copyright Taylor & Francis, Inc.
- Wielgus-Kutrowska, Beata,Bzowska, Agnieszka
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- Protection of the 2′-Hydroxy Function of Ribonucleosides as an Iminooxymethyl Propanoate and Its 2′-O-Deprotection through an Intramolecular Decarboxylative Elimination Process
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The design and implementation of 2′-hydroxy protecting groups for ribonucleosides is still a daunting challenge to overcome when assembling RNA (ribonucleic acid) sequences for therapeutic applications. The reaction of 2′-O-aminooxymethylribonucleosides with ethyl pyruvate results in the formation of 2′-O-iminooxymethyl ethyl propanoates. The cleavage of this type of 2′-O-protecting groups is demonstrated through saponification of the esters to 2′-O-iminooxymethyl propanoate salts, which, when needed, decarboxylate quantitatively at 55 °C in the presence of tetra-n-butylammonium fluoride or chloride in dimethyl sulfoxide (DMSO) to produce all four native ribonucleosides.
- Cie?lak, Jacek,Grajkowski, Andrzej,Ausín, Cristina,Beaucage, Serge L.
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- DIVERSE AND FLEXIBLE CHEMICAL MODIFICATION OF NUCLEIC ACIDS
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The present invention provides a method for chemically modifying a nucleic acid molecule using sulfinate reagents to increase stability in vitro and in vivo. Screening methods for nucleobase modifications that reduce cleavage of a nucleic acid molecule by a nuclease are also provided.
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Paragraph 0119-0123; 0131
(2020/05/12)
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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 PURIFICATION OF SYNTHETIC NUCLEIC ACID SEQUENCES
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The invention provides a compound of the formula (I), and a capture support of the formula (9), wherein R1, R2, R3, R6, A, B, D, E, J, K, Q, W, and Z are as defined herein. The invention also provides a method of purifying an oligonucleotide or an oligonucleotide analog composed of "b" nucleotides from a mixture comprising the oligonucleotide or oligonucleotide analog and at least one oligonucleotide or oligonucleotide analog composed of "a" nucleotides, wherein b ≠ a, comprising use of the compound and the capture support.
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(2018/09/25)
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- Chemistry of the 8-Nitroguanine DNA Lesion: Reactivity, Labelling and Repair
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The 8-nitroguanine lesion in DNA is increasingly associated with inflammation-related carcinogenesis, whereas the same modification on guanosine 3′,5′-cyclic monophosphate generates a second messenger in NO-mediated signal transduction. Very little is known about the chemistry of 8-nitroguanine nucleotides, despite the fact that their biological effects are closely linked to their chemical properties. To this end, a selection of chemical reactions have been performed on 8-nitroguanine nucleosides and oligodeoxynucleotides. Reactions with alkylating reagents reveal how the 8-nitro substituent affects the reactivity of the purine ring, by significantly decreasing the reactivity of the N2 position, whilst the relative reactivity at N1 appears to be enhanced. Interestingly, the displacement of the nitro group with thiols results in an efficient and specific method of labelling this lesion and is demonstrated in oligodeoxynucleotides. Additionally, the repair of this lesion is also shown to be a chemically feasible reaction through a reductive denitration with a hydride source.
- Alexander, Katie J.,McConville, Matthew,Williams, Kathryn R.,Luzyanin, Konstantin V.,O'Neil, Ian A.,Cosstick, Richard
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p. 3013 - 3020
(2018/02/09)
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- Enzymatic synthesis of ribo- and 2′-deoxyribonucleosides from glycofuranosyl phosphates: An approach to facilitate isotopic labeling
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Milligram quantities of α-D-ribofuranosyl 1-phosphate (sodium salt) (αR1P) were prepared by the phosphorolysis of inosine, catalyzed by purine nucleoside phosphorylase (PNPase). The αR1P was isolated by chromatography in >95% purity and characterized by 1H and 13C NMR spectroscopy. Aqueous solutions of αR1P were stable at pH 6.4 and 4 °C for several months. The isolated αR1P was N-glycosylated with different nitrogen bases (adenine, guanine and uracil) using PNPase or uridine phosphorylase (UPase) to give the corresponding ribonucleosides in high yield based on the glycosyl phosphate. This methodology is attractive for the preparation of stable isotopically labeled ribo- and 2′-deoxyribonucleosides because of the ease of product purification and convenient use and recycling of nitrogen bases. The approach eliminates the need for separate reactions to prepare individual furanose-labeled ribonucleosides, since only one ribonucleoside (inosine) needs to be labeled, if desired, in the furanose ring, the latter achieved by a high-yield chemical N-glycosylation. 2′-Deoxyribonucleosides were prepared from 2′-deoxyinosine using the same methodology with minor modifications.
- Zhang, Wenhui,Turney, Toby,Surjancev, Ivana,Serianni, Anthony S.
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p. 125 - 133
(2017/08/08)
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- Synthesis of Nucleosides through Direct Glycosylation of Nucleobases with 5-O-Monoprotected or 5-Modified Ribose: Improved Protocol, Scope, and Mechanism
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Simplifying access to synthetic nucleosides is of interest due to their widespread use as biochemical or anticancer and antiviral agents. Herein, a direct stereoselective method to access an expansive range of both natural and synthetic nucleosides up to a gram scale, through direct glycosylation of nucleobases with 5-O-tritylribose and other C5-modified ribose derivatives, is discussed in detail. The reaction proceeds through nucleophilic epoxide ring opening of an in situ formed 1,2-anhydrosugar (termed “anhydrose”) under modified Mitsunobu reaction conditions. The scope of the reaction in the synthesis of diverse nucleosides and other 1-substituted riboside derivatives is described. In addition, a mechanistic insight into the formation of this key glycosyl donor intermediate is provided.
- Downey, A. Michael,Pohl, Radek,Roithová, Jana,Hocek, Michal
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p. 3910 - 3917
(2017/03/27)
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- Chiral Nanozymes-Gold Nanoparticle-Based Transphosphorylation Catalysts Capable of Enantiomeric Discrimination
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Enantioselectivity in RNA cleavage by a synthetic metalloenzyme has been demonstrated for the first time. Thiols containing chiral ZnII-binding head groups have been self-assembled on the surface of gold nanoparticles. This results in the spontaneous formation of chiral bimetallic catalytic sites that display different activities (kcat) towards the enantiomers of an RNA model substrate. Substrate selectivity is observed when the nanozyme is applied to the cleavage of the dinucleotides UpU, GpG, ApA, and CpC, and remarkable differences in reactivity are observed for the cleavage of the enantiomerically pure dinucleotide UpU.
- Chen, Jack L.-Y.,Pezzato, Cristian,Scrimin, Paolo,Prins, Leonard J.
-
supporting information
p. 7028 - 7032
(2016/05/19)
-
- PRODUCTION METHOD OF NUCLEOSIDE COMPOUND
-
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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- Efficacy and site specificity of hydrogen abstraction from DNA 2-deoxyribose by carbonate radicals
-
The carbonate radical anion CO3?- is a potent reactive oxygen species (ROS) produced in vivo through enzymatic one-electron oxidation of bicarbonate or, mostly, via the reaction of CO2 with peroxynitrite. Due to the vitally essential role of the carbon dioxide/bicarbonate buffer system in regulation of physiological pH, CO3?- is arguably one of the most important ROS in biological systems. So far, the studies of reactions of CO3?- with DNA have been focused on the pathways initiated by oxidation of guanines in DNA. In this study, low-molecular products of attack of CO3?- on the sugar-phosphate backbone in vitro were analyzed by reversed phase HPLC. The selectivity of damage in double-stranded DNA (dsDNA) was found to follow the same pattern C4′ > C1′ > C5′ for both CO3?- and the hydroxyl radical, though the relative contribution of the C1′ damage induced by CO3?- is substantially higher. In single-stranded DNA (ssDNA) oxidation at C1′ by CO3?- prevails over all other sugar damages. An approximately 2000-fold preference for 8-oxoguanine (8oxoG) formation over sugar damage found in our study identifies CO3?- primarily as a one-electron oxidant with fairly low reactivity toward the sugar-phosphate backbone.
- Roginskaya, Marina,Moore,Ampadu-Boateng,Razskazovskiy
-
p. 1431 - 1437
(2015/11/09)
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- Guanidine-based polymer brushes grafted onto silica nanoparticles as efficient artificial phosphodiesterases
-
Polymer brushes grafted to the surface of silica nanoparticles were fabricated by atom-transfer radical polymerization (ATRP) and investigated as catalysts in the cleavage of phosphodiesters. The surfaces of silica nanoparticles were functionalized with an ATRP initiator. Surface-initiated ATRP reactions, in varying proportions, of a methacrylate moiety functionalized with a phenylguanidine moiety and an inert hydrophilic methacrylate species afforded hybrid nanoparticles that were characterized with potentiometric titrations, thermogravimetric analysis, and SEM. The activity of the hybrid nanoparticles was tested in the transesterification of the RNA model compound 2-hydroxypropyl para-nitrophenylphosphate (HPNP) and diribonucleoside monophosphates. A high catalytic efficiency and a remarkable effective molarity, thus overcoming the effective molarities previously observed for comparable systems, indicate the existence of an effective cooperation of the guanidine/guanidinium units and a high level of preorganization in the nanostructure. The investigated system also exhibits a marked and unprecedented selectivity for the diribonucleoside sequence CpA. The results presented open up the way for a novel and straightforward strategy for the preparation of supramolecular catalysts.
- Savelli, Claudia,Salvio, Riccardo
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p. 5856 - 5863
(2015/03/31)
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- Diguanidinocalix[4]arenes as effective and selective catalysts of the cleavage of diribonucleoside monophosphates
-
Calix[4]arenes derivatives 1 and 2, featuring two guanidine units at the upper rim, catalyze the transesterification of diribonucleoside monophosphates much more effectively than that of HPNP. Rate accelerations relative to the background range from 10su
- Salvio, Riccardo,Cacciapaglia, Roberta,Mandolini, Luigi,Sansone, Francesco,Casnati, Alessandro
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p. 34412 - 34416
(2014/11/12)
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- Formation of 8-S-L-cysteinylguanosine from 8-bromoguanosine and cysteine
-
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
-
p. 3864 - 3867
(2013/07/27)
-
- Permanent or reversible conjugation of 2′-O-or 5′-O- aminooxymethylated nucleosides with functional groups as a convenient and efficient approach to the modification of RNA and DNA sequences
-
2′-O-Aminooxymethyl ribonucleosides are prepared from their 3′,5′-disilylated 2′-O-phthalimidooxymethyl derivatives by treatment with NH4F in MeOH. The reaction of these novel ribonucleosides with 1-pyrenecarboxaldehyde results in the efficient formation of stable and yet reversible ribonucleoside 2′-conjugates in yields of 69-82. Indeed, exposure of these conjugates to 0.5M tetra-n-butylammonium fluoride (TBAF) in THF results in the cleavage of their iminoether functions to give the native ribonucleosides along with the innocuous nitrile side product. Conversely, the reaction of 5-cholesten-3-one or dansyl chloride with 2′-O-aminooxymethyl uridine provides permanent uridine 2′-conjugates, which are left essentially intact upon treatment with TBAF. Alternatively, 5′-O- aminooxymethyl thymidine is prepared by hydrazinolysis of its 3′-O-levulinyl-5′-O-phthalimidooxymethyl precursor. Pyrenylation of 5′-O-aminooxymethyl thymidine and the sensitivity of the 5′-conjugate to TBAF further exemplify the usefulness of this nucleoside for modifying DNA sequences either permanently or reversibly. Although the versatility and uniqueness of 2′-O-aminooxymethyl ribonucleosides in the preparation of modified RNA sequences is demonstrated by the single or double incorporation of a reversible pyrenylated uridine 2′-conjugate into an RNA sequence, the conjugation of 2′-O-aminooxymethyl ribonucleosides with aldehydes, including those generated from their acetals, provides reversible 2′-O-protected ribonucleosides for potential applications in the solid-phase synthesis of native RNA sequences. The synthesis of a chimeric polyuridylic acid is presented as an exemplary model.
- Cieslak, Jacek,Grajkowski, Andrzej,Ausin, Cristina,Gapeev, Alexei,Beaucage, Serge L.
-
p. 2312 - 2329
(2012/06/18)
-
- Posttranscriptional chemical functionalization of azide-modified oligoribonucleotides by bioorthogonal click and Staudinger reactions
-
Direct incorporation of azide groups into RNA oligonucleotides by in vitro transcription reactions in the presence of a new azide-modified UTP analogue, and subsequent posttranscriptional chemical labeling of azide-modified oligoribonucleotide transcripts by click and Staudinger reactions are described. This postsynthetic labeling protocol is robust and modular, and offers an alternative access to RNA labeled with biophysical probes.
- Rao, Harita,Sawant, Anupam A.,Tanpure, Arun A.,Srivatsan, Seergazhi G.
-
supporting information; experimental part
p. 498 - 500
(2012/02/03)
-
- 2'-O-AMINOOXYMETHYL NUCLEOSIDE DERIVATIVES FOR USE IN THE SYNTHESIS AND MODIFICATION OF NUCLEOSIDES, NUCLEOTIDES AND OLIGONUCLEOTIDES
-
Disclosed are O-protected compounds of the formula (I):wherein B is an optionally protected nucleobase, and R1-R3 are as described herein, a method of preparing such compounds, and a method of preparing oligonucleotides such as RNA starting from such compounds. The O-protected compounds have one or more advantages, for example, the 2'-O-protected compound is stable during the various reaction steps involved in oligonucleotide synthesis; the protecting group can be easily removed after the synthesis of the oligonucleotide, for example, by reaction with tetrabutylammonium fluoride; and/or the O-protected groups do not generate DNA/RNA alkylating side products, which have been reported during removal of 2'-O-(2-cyanoethyl)oxymethyl or 2'-O-[2-(4-tolylsulfonyl)ethoxymethyl groups under similar conditions.
- -
-
Page/Page column 44
(2012/10/18)
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- A microenvironment-sensitive fluorescent pyrimidine ribonucleoside analogue: Synthesis, enzymatic incorporation, and fluorescence detection of a DNA abasic site
-
Base-modified fluorescent ribonucleoside-analogue probes are valuable tools in monitoring RNA structure and function because they closely resemble the structure of natural nucleobases. Especially, 2-aminopurine, a highly environment-sensitive adenosine analogue, is the most extensively utilized fluorescent nucleoside analogue. However, only a few isosteric pyrimidine ribonucleoside analogues that are suitable for probing the structure and recognition properties of RNA molecules are available. Herein, we describe the synthesis and photophysical characterization of a small series of base-modified pyrimidine ribonucleoside analogues derived from tagging indole, N-methylindole, and benzofuran onto the 5-position of uracil. One of the analogues, based on a 5-(benzofuran-2-yl)pyrimidine core, shows emission in the visible region with a reasonable quantum yield and, importantly, displays excellent solvatochromism. The corresponding triphosphate substrate is effectively incorporated into oligoribonucleotides by T7 RNA polymerase to produce fluorescent oligoribonucleotide constructs. Steady-state and time-resolved spectroscopic studies with fluorescent oligoribonucleotide constructs demonstrate that the fluorescent ribonucleoside photophysically responds to subtle changes in its environment brought about by the interaction of the chromophore with neighboring bases. In particular, the emissive ribonucleoside, if incorporated into an oligoribonucleotide, positively reports the presence of a DNA abasic site with an appreciable enhancement in fluorescence intensity. The straightforward synthesis, amicability to enzymatic incorporation, and sensitivity to changes in the microenvironment highlight the potential of the benzofuran-conjugated pyrimidine ribonucleoside as an efficient fluorescent probe to investigate nucleic acid structure, dynamics, and recognition events. Uridine blue: T7 RNA polymerase effectively incorporates a polarity-sensitive fluorescent pyrimidine ribonucleotide analogue to produce emissive RNA oligonucleotides. The enzymatically generated fluorescent oligoribonucleotide reporter positively signals the presence of a DNA abasic site (see picture).
- Tanpure, Arun A.,Srivatsan, Seergazhi G.
-
experimental part
p. 12820 - 12827
(2011/12/16)
-
- Alkylating potential of α,β-unsaturated compounds
-
Alkylation reactions of the nucleoside guanosine (Guo) by the α,β-unsaturated compounds (α,β-UC) acrylonitrile (AN), acrylamide (AM), acrylic acid (AA) and acrolein (AC), which can act as alkylating agents of DNA, were investigated kinetically. The following conclusions were drawn: i) The Guo alkylation mechanism by AC is different from those brought about the other α,β-UC; ii) for the first three, the following sequence of alkylating potential was found: AN > AM > AA; iii) A correlation between the chemical reactivity (alkylation rate constants) of AN, AM, and AA and their capacity to form adducts with biomarkers was found. iv) Guo alkylation reactions for AN and AM occur through Michael addition mechanisms, reversible in the first case, and irreversible in the second. The equilibrium constant for the formation of the Guo-AN adduct is Keq (37 °C) = 5 × 10-4; v) The low energy barrier (≈10 kJ mol -1) to reverse the Guo alkylation by AN reflects the easy reversibility of this reaction and its possible correction by repair mechanisms; vi) No reaction was observed for AN, AM, and AA at pH 8.0. In contrast, Guo alkylation by AC was observed under cellular pH conditions. The reaction rate constants for the formation of the α-OH-Guo adduct (the most genotoxic isomer), is 1.5-fold faster than that of γ-OH-Guo. vii) a correlation between the chemical reactivity of α,β-UC (alkylation rate constants) and mutagenicity was found.
- Manso, Jose A.,Cespedes Camacho, Isaac F.,Calle, Emilio,Casado, Julio
-
scheme or table
p. 6226 - 6233
(2011/10/10)
-
- Radical-based alkylation of guanine derivatives in aqueous medium
-
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.
-
scheme or table
p. 3494 - 3498
(2011/06/25)
-
- RETRACTED ARTICLE: First prebiotic generation of a ribonucleotide from adenine, d-ribose and trimetaphosphate
-
Adenosine monophosphate isomers are obtained by self-assembling of adenine, d-ribose and trimetaphosphate in aqueous solution in good yields. This generation of a ribonucleotide from its three molecular components occurs in a one-pot reaction at room temperature for about 30-40 days and with high chemio-, regio-, and stereo-selectivity. Similar results are obtained with guanine. A mechanism is also proposed.
- Baccolini, Graziano,Boga, Carla,Micheletti, Gabriele
-
supporting information; experimental part
p. 3640 - 3642
(2011/05/04)
-
- Natural occurrence of 2′,5′-linked heteronucleotides in marine sponges
-
2′,5′-oligoadenylate synthetases (OAS) as a component of mammalian interferon-induced antiviral enzymatic system catalyze the oligomerization of cellular ATP into 2′,5′-linked oligoadenylates (2-5A). Though vertebrate OASs have been characterized as 2′-nucleotidyl transferases under in vitro conditions, the natural occurrence of 2′,5′-oligonucleotides other than 2-5A has never been demonstrated. Here we have demonstrated that OASs from the marine sponges Thenea muricata and Chondrilla nucula are able to catalyze in vivo synthesis of 2-5A as well as the synthesis of a series 2′,5′-linked heteronucleotides which accompanied high levels of 2′,5′-diadenylates. In dephosphorylated perchloric acid extracts of the sponges, these heteronucleotides were identified as A2′p5′G, A2′p5′U, A2′p5′C, G2′p5′A and G2′p5′U. The natural occurrence of 2′-adenylated NAD+ was also detected. In vitro assays demonstrated that besides ATP, GTP was a good substrate for the sponge OAS, especially for OAS from C. nucula. Pyrimidine nucleotides UTP and CTP were also used as substrates for oligomerization, giving 2′,5′-linked homo-oligomers. These data refer to the substrate specificity of sponge OASs that is remarkably different from that of vertebrate OASs. Further studies of OASs from sponges may help to elucidate evolutionary and functional aspects of OASs as proteins of the nucleotidyltransferase family.
- Lopp, Annika,Reintamm, Tonu,Kuusksalu, Anne,Tammiste, Indrek,Pihlak, Arno,Kelve, Merike
-
experimental part
p. 235 - 254
(2010/10/19)
-
- Photolabile N-hydroxypyrid-2(1H)-one derivatives of guanine nucleosides: A new method for independent guanine radical generation
-
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)
-
- MW-assisted Er(OTf)3-catalyzed mild cleavage of isopropylidene acetals in Tricky substrates
-
Erbium(III) trifluoromethane sulfonate is proposed as a very gentle Lewis acid catalyst in a MW-assisted chemoselective method for the cleavage of isopropylidene acetals in awkward substrates by using pure water as the solvent.
- Procopio, Antonio,Gaspari, Marco,Nardi, Monica,Oliverio, Manuela,Romeo, Roberto
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p. 1961 - 1964
(2008/09/19)
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- High-throughput five minute microwave accelerated glycosylation approach to the synthesis of nucleoside libraries
-
The Vorbrueggen glycosylation reaction was adapted into a one-step 5 min/130 °C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl inflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield ± SD was 26 ± 16%, and the average purity ± SD was 95 ± 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.
- Bookser, Brett C.,Raffaele, Nicholas B.
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p. 173 - 179
(2007/10/03)
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- Catalysis of diribonucleoside monophosphate cleavage by water soluble copper(II) complexes of calix[4]arene based nitrogen ligands
-
Calix[4]arenes functionalized at the 1,2-, 1,3-, and 1,2,3-positions of the upper rim with [12]ane-N3 ligating units were synthesized, and their bi- and trimetallic zinc(II) and copper(II) complexes were investigated as catalysts in the cleavage of phosphodiesters as RNA models. The results of comparative kinetic studies using monometallic controls indicate that the subunits of all of the zinc(II) complexes and of the 1,3-distal bimetallic copper(II) complex 7-Cu2 act as essentially independent monometallic catalysts. The lack of cooperation between metal ions in the above complexes is in marked contrast with the behavior of the 1,2-vicinal bimetallic copper(II) complex 6-Cu2, which exhibits high catalytic efficiency and high levels of cooperation between metal ions in the cleavage of HPNP and of diribonucleoside monophosphates NpN′. A third ligated metal ion at the upper rim does not enhance the catalytic efficiency, which excludes the simultaneous cooperation in the catalysis of the three metal ions in 8-Cu 3. Rate accelerations relative to the background brought about by 6-Cu2 and 8-Cu3 (1.0 mM catalyst, water solution, pH 7.0, 50 °C) are on the order of 104-fold, largely independent of the nucleobase structure, with the exception of the cleavage of diribonucleoside monophosphates in which the nucleobase N is uracil, namely UpU and UpG, for which rate enhancements rise to 105-fold. The rationale for the observed selectivity is discussed in terms of deprotonation of the uracil moiety under the reaction conditions and complexation of the resulting anion with one of the copper(II) centers.
- Cacciapaglia, Roberta,Casnati, Alessandro,Mandolini, Luigi,Reinhoudt, David N.,Salvio, Riccardo,Sartori, Andrea,Ungaro, Rocco
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p. 12322 - 12330
(2007/10/03)
-
- The radical-based reduction with (TMS)3SiH 'on water'
-
Reduction of different organohalides, bromonucleosides among them, was successfully carried out in yields ranging from 75% to quantitative, using (TMS)3SiH in a heterogeneous system with water as the solvent. Our procedure, employing 2-mercaptoethanol as the catalyst and the hydrophobic diazo-compound ACCN as the initiator, illustrates that (TMS)3SiH can be the radical-based reducing agent of choice in aqueous medium. (TMS) 3SiH does not suffer from any significant reaction with water and can safely be used with additional benefit, such as ease of purification and environmental compatibility. Georg Thieme Verlag Stuttgart.
- Postigo, Al,Ferreri, Carla,Navacchia, Maria Luisa,Chatgilialoglu, Chryssostomos
-
p. 2854 - 2856
(2007/10/03)
-
- Anti-HCV nucleoside derivatives
-
The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.
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-
-
- The pKa of the internucleotidic 2′-hydroxyl group in diribonucleoside (3′→5′) monophosphates
-
Ionization of the internucleotidic 2′-hydroxyl group in RNA facilitates transesterification reactions in Group I and II introns (splicing), hammerhead and hairpin ribozymes, self-cleavage in lariatRNA, and leadzymes and tRNA processing by RNase P RNA, as well as in some RNA cleavage reactions promoted by ribonucleases. Earlier, the pKa of 2′-OH in mono- and diribonucleoside (3′-5′) monophosphates had been measured under various nonuniform conditions, which make their comparison difficult. This work overcomes this limitation by measuring the pKa values for internucleotidic 2′-OH of eight different diribonucleoside (3′-5′) monophosphates under a set of uniform noninvasive conditions by 1H NMR. Thus the pKa is 12.31 (±0.02) for ApG and 12.41 (±0.04) for ApA, 12.73 (±0.04) for GpG and 12.71 (±0.08) for GpA, 12.77 (±0.03) for CpG and 12.88 (±0.02) for CpA, and 12.76 (±0.03) for UpG and 12.70 (±0.03) for UpA. By comparing the pKas of the respective 2′-OH of monomeric nucleoside 3′-ethyl phosphates with that of internucleotidic 2′-OH in corresponding diribonucleoside (3′→5′) monophosphates, it has been confirmed that the aglycons have no significant effect on the pKa values of their 2′-OH under our measurement condition, except for the internucleotidic 2′-OH of 9-adeninyl nucleotide at the 5′-end (ApA and ApG), which is more acidic by 0.3-0.4 pKα units.
- Acharya,Foeldesi,Chattopadhyaya
-
p. 1906 - 1910
(2007/10/03)
-
- Hydrolysis of diribonucleoside monophosphate diesters assisted by a manganese(II) complex
-
An Mn2+ complex with 2,2′:6′,2″-terpyridine (terpy) was found to promote the hydrolysis of NpN (NpN = diribonucleoside monophosphate diester) efficiently at pH 7.0 and 50 °C under ambient conditions. The structure of the Mn2+ complex involving a phosphodiester molecule, [(terpy)(dpp)MnII(μ-dpp) 2MnII(dpp)(terpy)], dpp = diphenyl phosphate anion, was established by X-ray crystallography, and the coordination mode of Mn 2+ to a phosphodiester molecule was considered.
- Yashiro, Morio,Higuchi, Maiko,Komiyama, Makoto,Ishii, Youichi
-
p. 1813 - 1817
(2007/10/03)
-
- Reliable chemical synthesis of oligoribonucleotides (RNA) with 2′-O-[(triisopropylsilyl)oxy]methyl(2′-O-tom)-protected phosphoramidites
-
A method for the introduction of the 2′-O-[(triisopropylsilyl)oxy]methyl (=tom) group into N-acetylated, 5′-O-dimethoxytritylated ribonucleosides is presented. The corresponding 2′-O-tom-protected phosphoramidite building blocks were obtained in pure form and were successfully employed for the routine synthesis of oligoribonucleotides on DNA synthesizers. Under DNA coupling conditions (2.5 min coupling time for a 1.5-μmol synthesis scale) and with 5-(benzylthio)-1H-tetrazole (BTT) as activator, 2′-O-tom-protected phosphoramidites exhibited average coupling yields >99.4%. The combination of N-acetyl and 2′-O-tom protecting groups allowed a reliable and complete two-step deprotection, first with MeNH2 in EtOH/H2O and then with Bu4NF in THF, without concomitant destruction of the product RNA sequences.
- Pitsch, Stefan,Weiss, Patrick A.,Jenny, Luzi,Stutz, Alfred,Wu, Xiaolin
-
p. 3773 - 3795
(2007/10/03)
-
- Some observations relating to the use of 1-aryl-4-alkoxypiperidin-4-yl groups for the protection of the 2′-hydroxy functions in the chemical synthesis of oligoribonucleotides
-
The comparative rates of acid-catalysed removal often 1-aryl-4-methoxypiperidin-4-yl 8 (R = Me) [including the previously reported Ctmp 5 and Fpmp 6] protecting groups for the 2′-hydroxy functions in oligoribonucleotide synthesis are discussed. These studies have led to the development of the 1-(4-chlorophenyl)-4-ethoxypiperidin-4-yl (Cpep) protecting group 8 (R = Et, R1 = R2 = H, R3 = Cl) which is both more stable than the Ctmp and Fpmp groups at pH 0.5 and more labile at pH 3.75. The influence of the ribonucleoside aglycone on the stability of the 2′-O-Fpmp and 2′-O-Ctmp protecting groups both at low and high pH is examined. The Royal Society of Chemistry 2000.
- Lloyd, Wayne,Reese, Colin B.,Song, Quanlai,Vandersteen, Anthony M.,Visintin, Cristina,Zhang, Pei-Zhou
-
p. 165 - 176
(2007/10/03)
-
- Rapid and highly base selective RNA cleavage by a dinuclear Cu(II) complex
-
A bis-Cu(II) complex based on a covalently linked terpyridine and bipyridine ligand system is shown to rapidly cleave bis-ribonucleotides with remarkable selectivity for adenine bases.
- Liu, Shanghao,Hamilton, Andrew D.
-
p. 587 - 588
(2007/10/03)
-
