362-76-5Relevant articles and documents
Phosphate-modified analogues of m7GTP and m7Gppppm7G - Synthesis and biochemical properties
Ziemniak, Marcin,Kowalska, Joanna,Lukaszewicz, Maciej,Zuberek, Joanna,Wnek, Katarzyna,Darzynkiewicz, Edward,Jemielity, Jacek
, p. 5369 - 5381 (2015)
The synthesis and biochemical properties of 17 new mRNA cap analogues are reported. Six of these nucleotides are m7GTP derivatives, whereas 11 are 'two headed' tetraphosphate dinucleotides based on a m7Gppppm7G structure. The compounds contain either a boranophosphate or phosphorothioate moiety in the nucleoside neighbouring position(s) and some of them possess an additional methylene group between β and γ phosphorus atoms. The compounds were prepared by divalent metal chloride-mediated coupling of an appropriate m7GMP analogue with a given P1,P2-di(1-imidazolyl) derivative. The analogues were evaluated as tools for studying cap-dependent processes in a number of biochemical assays, including determination of affinity to eukaryotic initiation factor eIF4E, susceptibility to enzymatic hydrolysis, and translational efficiency in vitro. The results indicate that modification in the phosphate chain can increase binding to cap-interacting proteins and provides higher resistance to degradation. Furthermore, modified derivatives of m7GTP were found to be potent inhibitors of cap-dependent translation in cell free systems.
Synthesis of 5'-deoxy-5'-thioguanosine-5'-monophosphorothioate and its incorporation into RNA 5'-termini.
Zhang,Cui,Sun
, p. 275 - 278 (2001)
[figure: see text] 5'-Deoxy-5'-thioguanosine-5'-monophosphorothioate (GSMP) was synthesized in four steps with 35% overall yield. GSMP serves as a good substrate for in vitro transcription with T7 RNA polymerase to yield 5'-GSMP-RNA, which was converted to 5'-HS-RNA by dephosphorylation with alkaline phosphatase. The thiol-reactive agents can be efficiently introduced into the 5'-terminus of RNA.
Release of bioactive volatiles from supramolecular hydrogels: Influence of reversible acylhydrazone formation on gel stability and volatile compound evaporation
Buchsnee Levrand, Barbara,Fieber, Wolfgang,Vigouroux-Elie, Florence,Sreenivasachary, Nampally,Lehn, Jean-Marie,Herrmann, Andreas
, p. 2906 - 2919 (2011)
In the presence of alkali metal cations, guanosine-5′-hydrazide (1) forms stable supramolecular hydrogels by selective self-assembly into a G-quartet structure. Besides being physically trapped inside the gel structure, biologically active aldehydes or ketones can also reversibly react with the free hydrazide functions at the periphery of the G-quartet to form acylhydrazones. This particularity makes the hydrogels interesting as delivery systems for the slow release of bioactive carbonyl derivatives. Hydrogels formed from 1 were found to be significantly more stable than those obtained from guanosine. Both physical inclusion of bioactive volatiles and reversible hydrazone formation could be demonstrated by indirect methods. Gel stabilities were measured by oscillating disk rheology measurements, which showed that thermodynamic equilibration of the gel is slow and requires several cooling and heating cycles. Furthermore, combining the rheology data with dynamic headspace analysis of fragrance evaporation suggested that reversible hydrazone formation of some carbonyl compounds influences the release of volatiles, whereas the absolute stability of the gel seemed to have no influence on the evaporation rates.
Design, synthesis and evaluation of N6-substituted 2-aminoadenosine-5′-N-methylcarboxamides as A3 adenosine receptor agonists
Devine, Shane M.,May, Lauren T.,Scammells, Peter J.
, p. 192 - 196 (2014)
A series of N6-substituted 2-aminoadenosine-5′-N- methylcarboxamides were synthesized from the versatile intermediate, O 6-(benzotriazol-1-yl)-2-amino-2′,3′-O- isopropylideneinosine-5′-N-methylcarboxamide (1). These compounds were evaluated as A3 adenosine receptor agonists in terms of their potency and receptor sub-type selectivity in a cAMP accumulation assay and a number of potent and selective compounds were identified. One such compound, 2-amino-N6-(3-chlorobenzyl)adenosine-5′-N-methylcarboxamide (3i), was over 500-fold selective for the A3AR over the other three adenosine receptor subtypes. This represents a significantly greater selectivity profile compared with the prototypical IB-MECA.
Synthesis of three regioisomeric (7-methoxychromenonyl)methyl guanosine 5′-phosphates
Faurel-Paul, Elodie,Yoshida, Kenta,Sepulcre, Magali,Dhimane, Hamid,Merrer, Yves Le
, p. 459 - 474 (2009)
Herein we describe the synthesis of three new (7-methoxychromenonyl)methyl 2-N-propionyl-2′,3′-isopropylideneguanosine 5′-phosphate diesters, potentially photolabile nucleotides, via an H-phosphonate strategy. The stability of these compounds toward acidic and basic conditions was evaluated during the nucleoside moiety deprotection. Copyright Taylor & Francis Group, LLC.
Modified GSMP synthesis greatly improves the disulfide crosslink of T7 run-off siRNAs with cell penetrating peptides
Schmitz, Katja,Hahn, Frank,Schepers, Ute
, p. 2959 - 2963 (2010)
Preventing intramolecular cyclization greatly improves 5′-deoxy- 5′-thioguanosine monophosphorothioate (GSMP) synthesis and its application as a potent initiator nucleotide for T7 run-off transcription of noncoding RNAs. GSMP was efficiently incorporated into the 5′-end of siRNA sense strands and the resulting thiol-modified siRNA was crosslinked with a free cysteine of cell penetrating peptide Penetratin as monitored by mass spectrometry. Cellular uptake and the knockdown potential of the peptide-coupled siRNA (pepsiRNA) were evaluated in primary cells. Georg Thieme Verlag Stuttgart - New York.
The synthesis of isopropylidene mRNA cap analogs modified with phosphorothioate moiety and their evaluation as promoters of mRNA translation
Warminski, Marcin,Kowalska, Joanna,Buck, Janina,Zuberek, Joanna,Lukaszewicz, Maciej,Nicola, Corina,Kuhn, Andreas N.,Sahin, Ugur,Darzynkiewicz, Edward,Jemielity, Jacek
, p. 3753 - 3758 (2013)
Synthetic mRNA cap analogs are valuable tools in the preparation of modified mRNA transcripts with improved translational activity and increased cellular stability, and have recently attracted more attention because of their great potential in therapeutic applications. We have synthesized and tested isopropylidene dinucleotide cap analogs bearing a phosphorothioate group at the β position of the 5′,5′-triphosphate bridge (two diastereomers of 2′,3′-iPr-m7GppSpG), as synthetically simpler alternatives to previously obtained phosphorothioate cap analogs. To evaluate the utility of the new compounds in biological systems we determined their affinity to translation initiation factor 4E (eIF4E), and tested their translational properties in rabbit reticulocyte lysates (RRL) and in human immature dendritic cells (hiDCs). In order to explain the properties of isopropylidene analogs we performed 1H NMR conformational analysis and correlated the absolute configuration at the β-phosphorous atom with previously synthesized m7GppSpG.
Nucleotide substrate specificity of anti-hepatitis C virus nucleoside analogs for human mitochondrial RNA polymerase
Ehteshami, Maryam,Zhou, Longhu,Amiralaei, Sheida,Shelton, Jadd R.,Cho, Jong Hyun,Zhang, Hongwang,Li, Hao,Lu, Xiao,Ozturk, Tugba,Stanton, Richard,Amblard, Franck,McBrayer, Tamara R.,Coats, Steven J.,Schinazi, Raymond F.
, (2017)
Nucleoside analog inhibitors (NAIs) are an important class of antiviral agents. Although highly effective, some NAIs with activity against hepatitis C virus (HCV) can cause toxicity, presumably due to off-target inhibition of host mitochondrial RNA polymerase (POLRMT). The in vitro nucleotide substrate specificity of POLRMT was studied in order to explore structure-activity relationships that can facilitate the identification of nontoxic NAIs. These findings have important implications for the development of all anti-RNA virus NAIs.
Persistent, well-defined, monodisperse, π-conjugated organic nanoparticles via G-quadruplex self-assembly
Gonzalez-Rodriguez, David,Janssen, Pim G. A.,Martin-Rapn, Rafael,Cat, Inge De,Feyter, Steven De,Schenning, Albertus P. H. J.,Meijer
, p. 4710 - 4719 (2010)
Several oligo(p-phenylene-vinylene) oligomers capped with a guanosine or a guanine moiety have been prepared via a palladium-catalyzed cross-coupling reaction. Their self-assembly, in both the absence and presence of alkaline salts, has been studied by means of different techniques in solution (NMR, MS, UV-vis, CD, fluorescence), solid state (X-ray diffraction), and on surfaces (STM, AFM). When no salt is added, these --conjugated molecules self-associate in a mixture of hydrogen-bonded oligomers, among which the G-quartet structure may be predominant if the steric hindrance around the guanine base becomes important. In contrast, in the presence of sodium or potassium salts, well-defined assemblies of eight functional molecules (8mers) can be formed selectively and quantitatively. In these assemblies, the --conjugated oligomers are maintained in a chirally tilted (J-type) stacking arrangement, which is manifested by negative Cotton effects, small bathochromic absorption and emission shifts, and fluorescence enhancements. Furthermore, these self-assembled organic nanostructures, ～1.5-2.0 nm high and 8.5 nm wide, exhibit an extraordinary stability to temperature or concentration changes in apolar media, and they can be transferred and imaged over solid substrates as individual nanoparticles, showing no significant dissociation or further aggregation.
Synthesis and evaluation of potential inhibitors of eIF4E cap binding to 7-methyl GTP
Ghosh, Phalguni,Park, Chunkyung,Peterson, Mark S.,Bitterman, Peter B.,Polunovsky, Vitaly A.,Wagner, Carston R.
, p. 2177 - 2180 (2005)
Cap-dependent translation is initiated by the binding of eIF4E to capped mRNA (m7GpppN). We have prepared a small library of 7-methyl guanosine nucleoside and nucleotide analogs and evaluated their ability to inhibit eIF4E binding to 7-methyl GTP with a competitive eIF4E binding immunoassay. 5′-H-Phosphonate derivatives in which the 2′- and 3′-riboside hydroxyls were tethered together by an isopropylidene group were shown to be a new class of inhibitors of eIF4E binding to capped mRNA.
