- Meteorite-catalyzed intermoleculartrans-glycosylation produces nucleosides under proton beam irradiation
-
Di-glycosylated adenines act as glycosyl donors in the intermoleculartrans-glycosylation of pyrimidine nucleobases under proton beam irradiation conditions. Formamide and chondrite meteorite NWA 1465 increased the yield and the selectivity of the reaction
- Bizzarri, Bruno Mattia,Fanelli, Angelica,Kapralov, Michail,Krasavin, Eugene,Saladino, Raffaele
-
p. 19258 - 19264
(2021/06/03)
-
- Conversion of: N- acyl amidines to amidoximes: A convenient synthetic approach to molnupiravir (EIDD-2801) from ribose
-
An efficient method is described for the preparation of molnupiravir (EIDD-2801) an antiviral agent via regioselective conversion of an N-acyl-nucleoside intermediate, generated through stereo and regioselective glycosylation of protected ribose and N4-acetyl cytosine, to an amidoxime. This method avoids use of expensive starting materials, enzymes, complex reagents, and cumbersome purification procedures.
- Ahmed, Ajaz,Ahmed, Qazi Naveed,Mukherjee, Debaraj
-
p. 36143 - 36147
(2021/12/04)
-
- DIVERSE AND FLEXIBLE CHEMICAL MODIFICATION OF NUCLEIC ACIDS
-
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.
- -
-
Paragraph 0119-0123; 0131
(2020/05/12)
-
- Identification of Flavin Mononucleotide as a Cell-Active Artificial N6-Methyladenosine RNA Demethylase
-
N6-Methyladenosine (m6A) represents a common and highly dynamic modification in eukaryotic RNA that affects various cellular pathways. Natural dioxygenases such as FTO and ALKBH5 are enzymes that demethylate m6A residues in mRNA. Herein, the first identification of a small-molecule modulator that functions as an artificial m6A demethylase is reported. Flavin mononucleotide (FMN), the metabolite produced by riboflavin kinase, mediates substantial photochemical demethylation of m6A residues of RNA in live cells. This study provides a new perspective to the understanding of demethylation of m6A residues in mRNA and sheds light on the development of powerful small molecules as RNA demethylases and new probes for use in RNA biology.
- Xie, Li-Jun,Yang, Xiao-Ti,Wang, Rui-Li,Cheng, Hou-Ping,Li, Zhi-Yan,Liu, Li,Mao, Lanqun,Wang, Ming,Cheng, Liang
-
supporting information
p. 5028 - 5032
(2019/03/17)
-
- Dehalogenation of Halogenated Nucleobases and Nucleosides by Organoselenium Compounds
-
Halogenated nucleosides, such as 5-iodo-2′-deoxyuridine and 5-iodo-2′-deoxycytidine, are incorporated into the DNA of replicating cells to facilitate DNA single-strand breaks and intra- or interstrand crosslinks upon UV irradiation. In this work, it is shown that the naphthyl-based organoselenium compounds can mediate the dehalogenation of halogenated pyrimidine-based nucleosides, such as 5-X-2′-deoxyuridine and 5-X-2′-deoxycytidine (X=Br or I). The rate of deiodination was found to be significantly higher than that of the debromination for both nucleosides. Furthermore, the deiodination of iodo-cytidines was found to be faster than that of iodo-uridines. The initial rates of the deiodinations of 5-iodocytosine and 5-iodouracil indicated that the nature of the sugar moiety influences the kinetics of the deiodination. For both the nucleobases and nucleosides, the deiodination and debromination reactions follow a halogen-bond-mediated and addition/elimination pathway, respectively.
- Mondal, Santanu,Mugesh, Govindasamy
-
p. 1773 - 1780
(2019/01/10)
-
- SOLID-PHASE PURIFICATION OF SYNTHETIC NUCLEIC ACID SEQUENCES
-
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.
- -
-
Page/Page column 41; 45
(2018/09/25)
-
- Selective aqueous acetylation controls the photoanomerization of α-cytidine-5′-phosphate
-
Nucleic acids are central to information transfer and replication in living systems, providing the molecular foundations of Darwinian evolution. Here we report that prebiotic acetylation of the non-natural, but prebiotically plausible, ribonucleotide α-cy
- Fernández-García, Christian,Grefenstette, Natalie M.,Powner, Matthew W.
-
supporting information
p. 4850 - 4853
(2018/05/23)
-
- Abiotic synthesis of purine and pyrimidine ribonucleosides in aqueous microdroplets
-
Aqueous microdroplets (a nucleobase (uracil, adenine, cytosine, or hypoxanthine) are electrosprayed from a capillary at +5 kV into a mass spectrometer at room temperature and 1 atm pressure with 3 mM divalent magnesium ion (Mg2+) as a catalyst. Mass spectra show the formation of ribonucleosides that comprise a four-letter alphabet of RNA with a yield of 2.5% of uridine (U), 2.5% of adenosine (A), 0.7% of cytidine (C), and 1.7% of inosine (I) during the flight time of ~50 μs. In the case of uridine, no catalyst is required. An aqueous solution containing guanine cannot be generated under the same conditions given the extreme insolubility of guanine in water. However, inosine can base pair with cytidine and thus substitute for guanosine. Thus, a full set of ribonucleosides to generate the purine–pyrimidine base pairs A-U and I-C are spontaneously generated in aqueous microdroplets under similar mild conditions.
- Nam, Inho,Nam, Hong Gil,Zare, Richard N.
-
-
- Vinyluridine as a Versatile Chemoselective Handle for the Post-transcriptional Chemical Functionalization of RNA
-
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.
-
p. 1529 - 1536
(2017/05/29)
-
- Synthesis of Nucleosides through Direct Glycosylation of Nucleobases with 5-O-Monoprotected or 5-Modified Ribose: Improved Protocol, Scope, and Mechanism
-
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
-
supporting information
p. 3910 - 3917
(2017/03/27)
-
- A prebiotically plausible synthesis of pyrimidine β-ribonucleosides and their phosphate derivatives involving photoanomerization
-
Previous research has identified ribose aminooxazoline as a potential intermediate in the prebiotic synthesis of the pyrimidine nucleotides with remarkable properties. It crystallizes spontaneously from reaction mixtures, with an enhanced enantiomeric excess if initially enantioenriched, which suggests that reservoirs of this compound might have accumulated on the early Earth in an optically pure form. Ribose aminooxazoline can be converted efficiently into α-ribocytidine by way of 2,2'-anhydroribocytidine, although anomerization to β-ribocytidine by ultraviolet irradiation is extremely inefficient. Our previous work demonstrated the synthesis of pyrimidine β-ribonucleotides, but at the cost of ignoring ribose aminooxazoline, using arabinose aminooxazoline instead. Here we describe a long-sought route through ribose aminooxazoline to the pyrimidine β-ribonucleosides and their phosphate derivatives that involves an extraordinarily efficient photoanomerization of α-2-thioribocytidine. In addition to the canonical nucleosides, our synthesis accesses β-2-thioribouridine, a modified nucleoside found in transfer RNA that enables both faster and more-accurate nucleic acid template-copying chemistry.
- Xu, Jianfeng,Tsanakopoulou, Maria,Magnani, Christopher J.,Szabla, Rafa?,?poner, Judit E.,?poner, Ji?í,Góra, Robert W.,Sutherland, John D.
-
p. 303 - 309
(2017/04/03)
-
- Chiral Nanozymes-Gold Nanoparticle-Based Transphosphorylation Catalysts Capable of Enantiomeric Discrimination
-
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)
-
- Protection of the 2′-Hydroxy Function of Ribonucleosides as an Iminooxymethyl Propanoate and Its 2′-O-Deprotection through an Intramolecular Decarboxylative Elimination Process
-
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.
-
p. 5817 - 5821
(2016/12/18)
-
- An efficient approach for conversion of 5-substituted 2-thiouridines built in RNA oligomers into corresponding desulfured 4-pyrimidinone products
-
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
-
supporting information
p. 3100 - 3104
(2015/07/08)
-
- 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)
-
- 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
-
p. 34412 - 34416
(2014/11/12)
-
- H-Bond activated glycosylation of nucleobases: Implications for prebiotic nucleoside synthesis
-
Glycosylation of nucleobases is achieved by heating metal free aqueous solution of nucleobase and sugar. It seems that abstraction of N 9/N1 H by C1′-OH promotes N 9/N1(nucleobase)-C1′ (sug
- Singh, Palwinder,Singh, Amrinder,Kaur, Jagroop,Holzer, Wolfgang
-
p. 3158 - 3161
(2014/01/06)
-
- METABOLITE BIOMARKERS FOR THE DETECTION OF ESOPHAGEAL CANCER USING MS
-
Results of studies of nucleosides in biofluid specimens from patients with esophageal adenocarcinoma and related disorders have identified five biomarkers of the conditions: 1-methyladenosine, N2,N2-dimethylguanosine, N2-methylguanosine, cytidine and uridine. In certain embodiments, methods of measuring these biomarkers and kits for measuring these biomarkers are provided.
- -
-
-
- Synthesis and cytotoxic activity of novel 5-substituted-1-(β-L- arabinofuranosyl) pyrimidine nucleosides
-
A series of new 5-halogeno-1-(β-L-arabinofuranosyl)uracils and their cytosine analogues were synthesized by halogenation of ara-L-uridine and ara-L-cytidine, respectively. The 5-(2-thienyl) and 5-halogenothienyl derivatives of both series were also prepared in excellent yields by Stille coupling followed by halogenation. All of these syntheses were based on benzoyl-protected derivatives. In vitro cytotoxicity experiments carried out using L1210 mouse leukemia cells showed that 5-(2-thienyl)- ara-L-uridine was the most potent compound of the new compounds; the majority of the analogues were not effective up to 200 μM concentrations. Copyright Taylor and Francis Group, LLC.
- Sendula, Robert,Orban, Erika,Hudecz, Ferenc,Sagi, Gyula,Jablonkai, Istvan
-
experimental part
p. 482 - 500
(2012/07/28)
-
- The mitochondrial amidoxime reducing component (mARC) is involved in detoxification of N-hydroxylated base analogues
-
The mitochondrial Amidoxime Reducing Component (mARC) is the newly discovered fourth molybdenum enzyme in mammals. All hitherto analyzed mammals express two mARC proteins, referred to as mARC1 and mARC2. Together with their electron transport proteins cytochrome b5 and NADH cytochrome b5 reductase, they form a three-component enzyme system and catalyze the reduction of N-hydroxylated prodrugs. Here, we demonstrate the reductive detoxification of toxic and mutagenic N-hydroxylated nucleobases and their corresponding nucleosides by the mammalian mARC-containing enzyme system. The N-reductive activity was found in all tested tissues with the highest detectable conversion rates in liver, kidney, thyroid, and pancreas. According to the presumed localization, the N-reductive activity is most pronounced in enriched mitochondrial fractions. In vitro assays with the respective recombinant three-component enzyme system show that both mARC isoforms are able to reduce N-hydroxylated base analogues, with mARC1 representing the more efficient isoform. On the basis of the high specific activities with N-hydroxylated base analogues relative to other N-hydroxylated substrates, our data suggest that mARC proteins might be involved in protecting cellular DNA from misincorporation of toxic N-hydroxylated base analogues during replication by converting them to the correct purine or pyrimidine bases, respectively.
- Krompholz, Nina,Krischkowski, Carmen,Reichmann, Debora,Garbe-Schoenberg, Dieter,Mendel, Ralf-R.,Bittner, Florian,Clement, Bernd,Havemeyer, Antje
-
p. 2443 - 2450
(2013/01/15)
-
- 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 9/13
(2012/10/18)
-
- 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.
-
experimental part
p. 2312 - 2329
(2012/06/18)
-
- Phosphorylating reagent-free synthesis of 5′-phosphate oligonucleotides by controlled oxidative degradation of their 5′-end
-
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
-
supporting information; body text
p. 2030 - 2033
(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)
-
- Nucleotide promiscuity of 3-phosphoglycerate kinase is in focus: Implications for the design of better anti-HIV analogues
-
The wide specificity of 3-phosphoglycerate kinase (PGK) towards its nucleotide substrate is a property that allows contribution of this enzyme to the effective phosphorylation (i.e. activation) of nucleotide-based pro-drugs against HIV. Here, the structural basis of the nucleotide-PGK interaction is characterised in comparison to other kinases, namely pyruvate kinase (PK) and creatine kinase (CK), by enzyme kinetic analysis and structural modelling (docking) studies. The results provided evidence for favouring the purine vs. pyrimidine base containing nucleotides for PGK rather than for PK or CK. This is due to the exceptional ability of PGK in forming the hydrophobic contacts of the nucleotide rings that assures the appropriate positioning of the connected phosphate-chain for catalysis. As for the d-/l-configurations of the nucleotides, the l-forms (both purine and pyrimidine) are well accepted by PGK rather than either by PK or CK. Here again the dominance of the hydrophobic interactions of the l-form of pyrimidines with PGK is underlined in comparison with those of PK or CK. Furthermore, for the l-forms, the absence of the ribose OH-groups with PGK is better tolerated for the purine than for the pyrimidine containing compounds. On the other hand, the positioning of the phosphate-chain is an even more important term for PGK in the case of both purines and pyrimidines with an l-configuration, as deduced from the present kinetic studies with various nucleotide-site mutants of PGK. These characteristics of the kinase-nucleotide interactions can provide a guideline for designing new drugs.
- Varga, Andrea,Chaloin, Laurent,Sagi, Gyula,Sendula, Robert,Graczer, Eva,Liliom, Karoly,Zavodszky, Peter,Lionne, Corinne,Vas, Maria
-
experimental part
p. 1863 - 1873
(2012/04/17)
-
- 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)
-
- Unprecedented gas-phase chiroselective logic gates
-
The gas-phase encounters between 2-aminobutane and proton-bound chiral resorcin[4]arene/nucleoside complexes behave in the gas phase as supramolecular "chiroselective logic gates" by releasing the nucleoside depending on the resorcin[4]arene and the 2-aminobutane configurations.
- Botta, Bruno,Fraschetti, Caterina,D'Acquarica, Ilaria,Sacco, Fabiola,Mattay, Jochen,Letzel, Matthias C.,Speranza, Maurizio
-
supporting information; experimental part
p. 1717 - 1719
(2011/05/03)
-
- 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)
-
- Simple method for fast deprotection of nucleosides by triethylamine- catalyzed methanolysis of acetates in aqueous medium
-
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
-
scheme or table
p. 859 - 866
(2010/09/11)
-
- Selective deacylation of peracylated ribonucleosides
-
A protocol for chemoselective deprotection of N,O-acylated ribonucleosides has been developed. Peracylated pyrimidine ribonucleosides subjected to guanidinium nitrate and NaOMe in MeOH/CH2Cl2 at 0 °C undergo high yielding O-deacylation, while even more pronounced chemoselectivity is observed with peracylated purine ribonucleosides as O5′-acyl groups are preserved. Nucleobase-protecting groups (ABz, CBz, GiBu, and UBz) are stable to these conditions, rendering this reagent mixture as a valuable addition to the collection of protecting group protocols in nucleoside chemistry.
- Rigoli, Jared W.,?stergaard, Michael E.,Canady, Kirsten M.,Guenther, Dale C.,Hrdlicka, Patrick J.
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supporting information; experimental part
p. 1751 - 1753
(2009/07/05)
-
- 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
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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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- COMPOUNDS FOR IMMUNOPOTENTIATION
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Methods of stimulating an immune response and treating patients responsive thereto with 3,4-di(1H-indol-3-yl)-1H-pyrrole-2,5-diones, staurosporine analogs, derivatized pyridazines, chromen-4-ones, indolinones, quinazolines, nucleoside analogs, and other small molecules are disclosed.
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Page/Page column 150
(2010/02/15)
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- A simple and efficient synthesis of puromycin, 2,2′-anhydro- pyrimidine nucleosides, cytidines and 2′,3′-anhydroadenosine from 3′,5′-O-sulfinyl xylo-nucleosides
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Synthesis of antibiotics, puromycin and 3 ′-amino-3 ′-deoxy-N 6 ,N 6 -dimethyladenosine 11 was achieved by utilizing the cyclic sulfite 6a of the xylo -3 ′,5 ′-dihydroxy group as a new protective group. The key synthetic step is the deprotection of the sulfite moiety through the intramolecular cyclization of 2-α-carbamate 7 . In a similar manner, 2,2 ′-anhydro-pyrimidine nucleosides 15 , ribo -cytidines 17 and 2 ′,3 ′-anhydroadenosine 14 were prepared in high yields from the corresponding sulfites 4 , 5 , and 6b , respectively. Copyright Taylor & Francis Group, LLC.
- Takatsuki, Ken-Ichi,Ohgushi, Sumito,Kohmoto, Shigeo,Kishikawa, Keiki,Yamamoto, Makoto
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p. 719 - 734
(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
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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)
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- Antisense modulation of CDC14A expression
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Antisense compounds, compositions and methods are provided for modulating the expression of CDC14A. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding CDC14A. Methods of using these compounds for modulation of CDC14A expression and for treatment of diseases associated with expression of CDC14A are provided.
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Page/Page column 16
(2010/02/06)
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- A new protecting group '3′,5′-O-sulfinyl' for xylo-nucleosides. A simple and efficient synthesis of 3′-amino-3′-deoxyadenosine (a puromycin intermediate), 2,2′-anhydro-pyrimidine nucleosides and 2′,3′-anhydro-adenosine
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We developed a new protecting group, the cyclic sulfite for the protection of the 3′,5′-dihydroxy group of nucleosides. Seven cyclic sulfites, 4a-c, 5a-b, and 6a-b were prepared in high yields from the corresponding xylo-uridines 1 and 2, and xylo-adenosines 3 with thionyl chloride, respectively. Synthesis of the puromycin intermediate 8 was carried out by deprotection of the sulfite moiety through an intramolecular cyclization of the 2′-α-carbamate 7.
- Takatsuki, Ken-Ichi,Yamamoto, Makoto,Ohgushi, Sumito,Kohmoto, Shigeo,Kishikawa, Keiki,Yamashita, Haruhiro
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p. 137 - 140
(2007/10/03)
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- A new and efficient synthetic method for 15N3-labeled cytosine nucleosides: Dimroth rearrangement of cytidine N3-oxides
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The treatment of 15N4-labeled cytidine N 3-oxide and 15N4-labeled 2′-deoxycytidine N3-oxide, prepared from the appropriate unprotected uridines in three reaction steps, with benzyl bromide in the presence of excess lithium methoxide allowed the smooth occurrence of their Dimroth rearrangement even under mild conditions leading to the corresponding 15N 3-labeled uridine 4-O-benzyloximes which can easily undergo the reductive N-O bond cleavage to give the desirable 15N 3-labeled cytosine nucleosides in high total yields.
- Sako, Magoichi,Kawada, Hiroyoshi
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p. 8148 - 8150
(2007/10/03)
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- Anti-HCV nucleoside derivatives
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The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.
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- Hydrolysis of diribonucleoside monophosphate diesters assisted by a manganese(II) complex
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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
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p. 1813 - 1817
(2007/10/03)
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- 2'modified oligonucleotides
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Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2′-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of diseases caused by various viruses and other causative agents is provided.
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- Zinc finger peptide cleavage of nucleic acids
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Selective cleavage of single stranded nucleic acids can be effected by contacting the nucleic acid with a zinc finger peptide in dimeric form. Dimerization results from diminution or elimination of zinc from the peptide, such that easily controllable and highly selective cleavage may be realized.
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- Photolabile groups for exocyclic amino and O6/N-1 lactam protection in oligonucleotide synthesis
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The use of o-nitrobenzyloxycarbonyl (nCbz) for direct protection of exocyclic amino function of nucleosides viz. adenosine, cytidine and deoxyguanosine using o-nitrobenzyl-p-nitrophenyl carbonate as a reagent and O6-derivatization of deoxyguanosine with o-nitrobenzyl (nBzl) using o-nitrobenzyldiazomethane as a reagent is being reported. Both these protected groups could be cleaved by irradiation at 354nm to yield valuable building blocks for oligonucleotide synthesis.
- Misra, Arvind,Tripathi, Snehlata,Misra, Krishna
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p. 1454 - 1459
(2007/10/03)
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- Reliable chemical synthesis of oligoribonucleotides (RNA) with 2′-O-[(triisopropylsilyl)oxy]methyl(2′-O-tom)-protected phosphoramidites
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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
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p. 3773 - 3795
(2007/10/03)
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- 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
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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
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p. 165 - 176
(2007/10/03)
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- Oligoribonucleotides and ribonucleases for cleaving RNA
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Oligomeric compounds including oligoribonucleotides and oligoribonucleosides are provided that have subsequences of 2'-pentoribofuranosyl nucleosides that activate dsRNase. The oligoribonucleotides and oligoribonucleosides can include substituent groups for increasing binding affinity to complementary nucleic acid strand as well as substituent groups for increasing nuclease resistance. The oligomeric compounds are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics. Also included in the invention are mammalian ribonucleases, i.e., enzymes that degrade RNA, and substrates for such ribonucleases. Such a ribonuclease is referred to herein as a dsRNase, wherein "ds" indicates the RNase's specificity for certain double-stranded RNA substrates. The artificial substrates for the dsRNases described herein are useful in preparing affinity matrices for purifying mammalian ribonuclease as well as non-degradative RNA-binding proteins.
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- Rapid and highly base selective RNA cleavage by a dinuclear Cu(II) complex
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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.
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p. 587 - 588
(2007/10/03)
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- L-Ribonucleosides from L-xylose
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L-Xylose was converted into a L-ribose derivative via an oxidation/reduction procedure. The L-ribosyl donor was submitted to a glycosidation reaction according to Vorbruggen's conditions to give L- ribonucleosides (L-uridine, L-cytidine, L-adenosine and L-guanosine) in high yield.
- Moyroud, Elisabeth,Strazewski, Peter
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p. 1277 - 1284
(2007/10/03)
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