- Preparation method of 5′-O-(4,4'-dimethoxytriphenylmethyl)-N2-isobutyryl guanosine
-
The present invention discloses a method for preparing 5 '-O- (4,4'-dimethoxytriphenylmethyl)-N2-isobutyryl guanosine, after the preparation of N2-isobutyryloylguanosine with guanosine as the starting material, dmt-Cl was added to participate in the react
- -
-
Paragraph 0009; 0013-0036
(2022/01/10)
-
- Compositions and Methods for Reverse Automated Nucleic Acid Synthesis
-
Methods for reverse automated nucleic acid synthesis, and 5′-H-phosphonates suitable for use in the same, as well as methods for making 5′-H-phosphonates, are described.
- -
-
Paragraph 0111
(2019/10/29)
-
- CYCLIC DINUCLEOTIDES AS STING AGONISTS
-
Disclosed are compounds, compositions and methods for treating of diseases, syndromes, or disorders that are affected by the modulation of STING. Such compounds are represented by Formula (I) as follows: wherein R, R1B, R1C, R2B
- -
-
Page/Page column 110
(2018/08/20)
-
- New tools in nucleoside toolbox of tick-borne encephalitis virus reproduction inhibitors
-
Design and development of nucleoside analogs is an established strategy in the antiviral drug discovery field. Nevertheless, for many viruses the coverage of structure-activity relationships (SAR) in the nucleoside chemical space is not sufficient. Here we present the nucleoside SAR exploration for tick-borne encephalitis virus (TBEV), a member of Flavivirus genus. Promising antiviral activity may be achieved by introduction of large hydrophobic substituents in the position 6 of adenosine or bulky silyl groups to the position 5′. Introduction of methyls to the ribose moiety does not lead to inhibition of TBEV reproduction. Possible mechanisms of action of these nucleosides include the inhibition of viral entry or interaction with TBEV non-structural protein 5 methyltransferase or RNA-dependent RNA polymerase domains.
- Orlov, Alexey A.,Drenichev, Mikhail S.,Oslovsky, Vladimir E.,Kurochkin, Nikolay N.,Solyev, Pavel N.,Kozlovskaya, Liubov I.,Palyulin, Vladimir A.,Karganova, Galina G.,Mikhailov, Sergey N.,Osolodkin, Dmitry I.
-
supporting information
p. 1267 - 1273
(2017/06/19)
-
- Synthesis and in vitro stability of nucleoside 5′-phosphonate derivatives
-
Nucleoside derivatives are largely synthesized and tested to investigate their influence on platelet aggregation. It's well known that P2Y receptors play an important role in the regulation of platelet function and, as consequence, in controlling atherothrombotic events. The research of compounds that antagonize P2Y1 and, in particular, P2Y12 receptors is of great interest in the aim to obtain platelet aggregation inhibitors that are effective in the prevention and treatment of arterial thrombosis. In this study we present the synthesis and in vitro metabolic stability in human blood and rat liver homogenate of a new class of nucleoside derivatives, in particular 5′-phosphonate adenosine, inosine, guanosine and thioadenosine analogues also modified at the ribose moiety. On the basis of the results obtained we can hypothesize compounds 4 and 18 to have in vivo a relatively high stability.
- Vertuani, Silvia,Baldisserotto, Anna,Varani, Katia,Borea, Pier Andrea,De Marcos Maria Cruz, Bonache,Ferraro, Luca,Manfredini, Stefano,Dalpiaz, Alessandro
-
supporting information; experimental part
p. 202 - 209
(2012/09/07)
-
- Synthesis of oligoribonucleotides containing 2'-o-methoxymethyl group by the phosphotriester method
-
An effective procedure for the synthesis of ribonucleotide monomers containing a 2'-methoxymethyl-modifying group was developed. These monomers were used for the synthesis of RNA fragments by the solid-phase phosphotriester method under O-nucleophilic intramolecular catalysis. The properties of 2'-methoxymethyl-containing oligoribonucleotides were examined. Copyright Taylor and Francis Group, LLC.
- Efimov, Vladimir A.,Aralov, Andrey V.,Chakhmakhcheva, Oksana G.
-
p. 565 - 576
(2011/12/22)
-
- COMPOUNDS FOR TREATING BACTERIAL INFECTIONS
-
The present invention relates to a novel class of guanine nucleotide analogs which inhibit RelA and Relseq synthetic activity and which possess anti-bacterial activity. The present invention also relates to pharmaceutical compositions that include such compounds, and to methods of use of such compounds or compositions for combating bacteria and treating bacterial infections.
- -
-
Page/Page column 30
(2011/04/25)
-
- Design and synthesis of α-carboxy phosphononucleosides
-
Rhodium catalyzed O-H insertion reactions employing α- diazophosphonate 20 with appropriately protected thymidine, uridine, cytosine, adenosine and guanosine derivatives leads to novel 5′-phosphononucleoside derivatives. Deprotection led to a novel series of phosphono derivatives bearing a carboxylic acid moiety adjacent to the phosphonate group with potential antiviral and/or anticancer activity. The phosphononucleosides bearing an α-carboxylic acid group are envisaged as potential diphosphate mimics. Conversion to mono- and diphosphorylated phosphononucleosides has been effected for evaluation as nucleoside triphosphate mimics. Most of the novel phosphononucleosides proved to be inactive against a variety of DNA and RNA viruses. Only the phosphono AZT derivatives 56-59 showed weak activity against HIV-1 and HIV-2.
- Debarge, Sebastien,Balzarini, Jan,Maguire, Anita R.
-
scheme or table
p. 105 - 126
(2011/04/17)
-
- ppGpp analogues inhibit synthetase activity of Rel proteins from Gram-negative and Gram-positive bacteria
-
A prominent feature of the stringent response is the accumulation of two unusual phosphorylated derivatives of GTP and GDP (pppGpp: 5′-triphosphate-3′-diphosphate, and ppGpp: 5′-3′-bis-diphosphate), collectively called (p)ppGpp, within a few seconds after the onset of amino-acid starvation. The synthesis of these 'alarmone' compounds is catalyzed by RelA homologues. Other features of the stringent response include inhibition of stable RNA synthesis and modulation of transcription, replication, and translation. (p)ppGpp accumulation is important for virulence induction, differentiation and antibiotic resistance. We have synthesized a group of (p)ppGpp analogues and tested them as competitive inhibitors of Rel proteins in vitro. 2′-Deoxyguanosine-3′-5′-di(methylene bisphosphonate) [compound (10)] was found as an inhibitor that reduces ppGpp formation in both Gram-negative and Gram-positive bacteria. In silico docking together with competitive inhibition analysis suggests that compound (10) inhibits activity of Rel proteins by competing with GTP/GDP for its binding site. As Rel proteins are completely absent in mammalians, this appears to be a very attractive approach for the development of novel antibacterial agents.
- Wexselblatt, Ezequiel,Katzhendler, Jehoshua,Saleem-Batcha, Raspudin,Hansen, Guido,Hilgenfeld, Rolf,Glaser, Gad,Vidavski, Roee R.
-
experimental part
p. 4485 - 4497
(2010/08/22)
-
- Synthesis of guanosine 5′-conjugates and their use as initiator molecules for transcription priming
-
We have synthesised two guanosine derivatives that are linked to biotinylated adenosine moieties by using two different strategies, one that includes synthetic steps on the solid phase and another one that is performed entirely in solution. The synthesised derivatives were shown to function as initiator molecules in transcription priming experiments. The incorporation efficiency was determined to be approximately 2%. Even though this value is rather low, the use of either molecule in selection experiments seems reasonable. Basically, RNA libraries with sequence complexities of 10 15 to 1016 can be generated. Labelling of such a library with our initiator molecule would still produce 1013 to 10 14 labelled/functionalised sequences, and thus sufficient sequence space for selection. The Royal Society of Chemistry.
- Wolf, Joern,Dombos, Valeska,Appel, Bettina,Mueller, Sabine
-
supporting information; experimental part
p. 899 - 907
(2008/10/09)
-
- Synthesis, characterization, and biological properties of small branched RNA fragments containing chiral (Rp and Sp) 2′,5′-phosphorothioate linkages
-
Synthetic branched RNA fragments were prepared to examine the stereochemical requirements for hydrolysis of RNA lariats by the yeast debranching enzyme (yDBR). Specifically, two branched trinucleoside diphosphates and a tetranucleoside triphosphate contai
- Mourani, Rawan,Damha, Masad J.
-
p. 203 - 229
(2007/10/03)
-
- RIBONUCLEIC ACID COMPOUND AND METHOD OF LIQUID-PHASE SYNTHESIS OF OLIGONUCLEIC ACID COMPOUND
-
A novel phosphotriesterified ribonucleic acid compound which is important for liquid-phase synthesis of oligo-RNA is provided. Examples of the ribonucleic acid compound of the invention may include ribonucleic acid compounds represented by the following general formula: (wherein B represents adenine, guanine, cytosine or uracil or a modified form thereof; R21 represents aryl which may be substituted or a monocyclic or bicyclic heterocyclic group which may be substituted; R20 represents H or alkyl which may be substituted; and R1 represents a protecting group which can be removed at 90% or more at a temperature in the range from 0°C to 60°C under acidic conditions at a pH value from 2 to 4 within 24 hours).
- -
-
Page/Page column 17
(2010/11/24)
-
- NOVEL GUANOSINE DERIVATIVES AND USE THEREOF
-
It is intended to provide a novel monomer unit by which Z type DNA can be more effectively stabilized, a reagent for integrating this monomer unit into an oligonucleotide, and a method of stabilizing Z type DNA by using the reagent. Namely, a guanosine de
- -
-
Page/Page column 5
(2008/06/13)
-
- Improved and Reliable Synthesis of 3′-Azido-2′,3′ -dideoxyguanosine Derivatives
-
An improved synthesis of N2-protected-3′-azido-2′ ,3′-dideoxyguinosine 20 and 23 is described. Deoxygenation of 2′-O-alkyl (and/or aryl) sulfonyl-5′-dimethoxytritylguanosine coupled with [1,2]-hydride shift rearrangement gave protected 9-(2-deoxythreo-pentofuranosyl)guanines (10, 12 and 16). This rearrangement was accomplished in high yield with a high degree of stereoselectivity using lithium triisobutylborohydride (L-Selectride R). Compounds 10, 12 and 16 were transformed into 3′-O-mesylates (18 and 21), which can be used for 3′-substitution. The 3′-azido nucleosides were obtained by treatment of 18 and 21 with lithium azide. This procedure is reproducible with a good overall yield.
- Timoshchuk, Victor A.,Hogrefe, Richard I.,Vaghefi, Morteza M.
-
p. 171 - 181
(2007/10/03)
-
- 8-Methylguanosine: A Powerful Z-DNA Stabilizer
-
Various modified guanine derivatives were synthesized and introduced into G4 of d(CGCGCG)2 to evaluate their capacity to stabilize Z-form DNA. It was found that the incorporation of 8-methylguanosine (m 8rG) in oligonucleo
- Xu, Yan,Ikeda, Reiko,Sugiyama, Hiroshi
-
p. 13519 - 13524
(2007/10/03)
-
- A ribozyme with michaelase activity: synthesis of the substrate precursors.
-
The ability to generate RNA molecules that can catalyze complex organic transformations not only facilitates the reconstruction and plausibility of possible prebiotic reaction pathways but is also crucial for elucidating the potential of the application of RNA catalysts in organic syntheses. Iterative RNA selection previously identified a ribozyme that catalyzes the Michael addition of a cysteine thiol to an alpha,beta-unsaturated amide. This reaction is chemically similar to the rate limiting step of the thymidylate synthase reaction, which is the corresponding reaction of a cysteine thiol to the double-bond of the uracil nucleobase. Here we provide a detailed description of the synthesis of the ribozyme substrates and the substrate oligonucleotides used for its characterization and the investigation of the background reaction. We also describe the further characterization of the ribozyme with respect to substrate specificity. We show that the thiol group of the cysteine nucleophile is essential for the reaction to proceed. When substituted for a thiomethyl group, no reaction takes place.
- Eisenfuehr, Alexander,Arora, Paramjit S,Sengle, Gerhard,Takaoka, Leo R,Nowick, James S,Famulok, Michael
-
p. 235 - 249
(2007/10/03)
-
- Uncharged polynucleotide-binding polymers
-
A composition of polymer molecules effective to bind, with substantially uniform binding affinity, to a single-stranded polynucleotide containing a target sequence of bases. The polymer molecules are composed of a sequence of base-pairing moieties effective to hydrogen bond to corresponding, complementary bases in the target sequence, under selected binding conditions, and a predominantly uncharged, achiral backbone supporting the base-pairing moieties at positions and in orientations which allow hydrogen bonding between the pairing moieties of the polymer and the corresponding complementary bases in the target sequence. The composition has diagnostic uses, in a solid-support assay system, and therapeutic uses involving inhibition or inactivation of target polynucleotides.
- -
-
-
- REGIOSELECTIVE PROTECTION OF CARBOHYDRATE DERIVATIVES. PART. 20. SIMPLE, EFFICIENT 2'-O-DEACYLATION OF FULLY ACYLATED PURINE AND PYRIMIDINE RIBONUCLEOSIDES THROUGH tert-BUTOXIDE
-
A simple treatment of fully aroylated purine and pyrimidine ribonucleosides with pulverized potassium tert-butoxide in tetrahydrofuran (THF) or dichloromethane under a controlled condition gave a mixture of the corresponding di-O-aroyl derivatives in which 2'-OH derivatives are preponderant over 3'-OH derivatives; 3',5'-di-O-benzoyluridine, N4,3',5'-tribenzoylcytidine, N4,3',5'-tri-O-toluoylcytidine, N2,3',5'-tribenzoylguanosine, and N2,isobutyryl-3',5'-di-O-benzoylguanosine were obtained crystalline in 80 percent, 78 percent, 72 percent, 67 percent, and 65 percent yields, respectively.
- Nishino, Shigeyoshi,Takamura, Hatsuko,Ishido, Yoshiharu
-
p. 1995 - 2004
(2007/10/02)
-
- Nucleosides, XXXVII. - Synthesis and Properties of 2'-O- and 3'-O-(tert-Butyldimethylsilyl)-5'-O-(4-methoxytrityl)- and 2',3'-Bis(O-tert-butyldimethylsilyl)ribonucleosides - Starting Materials for Oligoribonucleotide Syntheses
-
The synthesis of aminoacylated 5'-O-(4-methoxytrityl)ribonucleosides of adenosine (1), guanosine (9), cytidine (31), uridine (17), and 5,6-dihydrouridine (23) have been optimized and these compounds (4, 12, 33, 18 and 24) silylated by tert-butyldimethylsilyl chloride.The corresponding 2'- and 3'-mono-O- as well as 2',3'-bis-O-(tert-butyldimethylsilyl) derivatives have been isolated by combination of chromatographical methods and fractional crystallization procedures in preparative scale.The characterization of the newly synthesized compounds was achieved by UV and 13C-NMR spectra.
- Flockerzi, Dieter,Silber, Gunter,Charubala, Ramamurthy,Schlosser, Wilhelm,Varma, Rajendra Singh,et al.
-
p. 1568 - 1585
(2007/10/02)
-