171284-47-2Relevant academic research and scientific papers
How to find the optimal partner - Studies of snurportin 1 interactions with U snRNA 5′ TMG-cap analogues containing modified 2-amino group of 7-methylguanosine
Piecyk, Karolina,Niedzwiecka, Anna,Ferenc-Mrozek, Aleksandra,Lukaszewicz, Maciej,Darzynkiewicz, Edward,Jankowska-Anyszka, Marzena
, p. 4660 - 4668 (2015)
Snurportin 1 is an adaptor protein that mediates the active nuclear import of uridine-rich small nuclear RNAs (U snRNA) by the importin-β receptor pathway. Its cellular activity influences the overall transport yield of small ribonucleoprotein complexes containing N2,N2,7-trimethylguanosine (TMG) capped U snRNA. So far little is still known about structural requirements related to molecular recognition of the trimethylguanosine moiety by snurportin in solution. Since these interactions are of a great biomedical importance, we synthesized a series of new 7-methylguanosine cap analogues with extended substituents at the exocyclic 2-amino group to gain a deeper insight into how the TMG-cap is adapted into the snurportin cap-binding pocket. Prepared chemical tools were applied in binding assays using emission spectroscopy. Surprisingly, our results revealed strict selectivity of snurportin towards the TMG-cap structure that relied mainly on its structural stiffness and compactness.
CYCLIC DINUCLEOTIDES AS ANTICANCER AGENTS
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Paragraph 1568; 1569; 1570, (2019/02/13)
The present invention is directed to compounds of the formulae I, II and III as shown below wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.
Solid-phase synthesis and hybrization behavior of partially 2′/3′-O-acetylated RNA oligonucleotides
Xu, Jianfeng,Duffy, Colm D.,Chan, Christopher K. W.,Sutherland, John D.
, p. 3311 - 3326 (2014/05/06)
Synthesis of partially 2′/3′-O-acetylated oligoribonucleotides has been accomplished by using a 2′/3′-O-acetyl orthogonal protecting group strategy in which non-nucleophilic strong-base (DBU) labile nucleobase protecting groups and a UV-light cleavable linker were used. Strong-base stability of the photolabile linker allowed on-column nucleobase and phosphate deprotection, followed by a mild cleavage of the acetylated oligonucleotides from the solid support with UV light. Two 17nt oligonucleotides, which were synthesized possessing one specific internal 2′- or 3′-acetyl group, were used as synthetic standards in a recent report from this laboratory detailing the prebiotically plausible ligation of RNA oligonucleotides. In order to further investigate the effect of 2′/3′-O-acetyl groups on the stability of RNA duplex structure, two complementary bis-acetylated RNA oligonucleotides were also expediently obtained with the newly developed protocols. UV melting curves of 2′-O-acetylated RNA duplexes showed a consistent ～3.1 °C decrease in Tm per 2′-O-acetyl group.
Synthesis of N2-modified 7-methylguanosine 5′- monophosphates as nematode translation inhibitors
Piecyk, Karolina,Davis, Richard E.,Jankowska-Anyszka, Marzena
experimental part, p. 4781 - 4789 (2012/08/29)
Preparative scale synthesis of 14 new N2-modified mononucleotide 5′ mRNA cap analogues was achieved. The key step involved use of an SNAr reaction with protected 2-fluoro inosine and various primary and secondary amines. The derivatives were tested in a parasitic nematode, Ascaris suum, cell-free system as translation inhibitors. The most effective compound with IC50 ～0.9 μM was a N2-p-metoxybenzyl-7- methylguanosine-5′-monophosphate 35.
A modified guanosine phosphoramidite for click functionalization of RNA on the sugar edge
Seidu-Larry, Salifu,Krieg, Bettina,Hirsch, Markus,Helm, Mark,Domingo, Olwen
supporting information, p. 11014 - 11016 (2013/01/15)
A propargyl containing guanosine phosphoramidite was synthesized and incorporated into siRNA, enabling click-ligation with an azido fluorophore onto the nucleobase sugar edge. Duplex stability was not affected by labeling at this new site, which allowed deconvolution of the effects of label, structure and attachment site on RNAi activity.
Synthesis of 13C- and 14C-labeled dinucleotide mRNA cap analogues for structural and biochemical studies
Piecyk, Karolina,Davis, Richard E.,Jankowska-Anyszka, Marzena
experimental part, p. 4391 - 4395 (2012/09/21)
Herein we describe the first simple and short method for specific labeling of mono- and trimethylated dinucleotide mRNA cap analogues with 13C and 14C isotopes. The labels were introduced within the cap structures either at the N7 for monomethylguanosine cap or N7 and N2 position for trimethylguanosine cap. The compounds designed for structural and biochemical studies will be useful tools for better understanding the role of the mRNA cap structures in pre-mRNA splicing, nucleocytoplasmic transport, translation initiation and mRNA degradation.
Synthesis of Nucleoside Libraries on Solid Support. II. 2,6,8-Trisubstituted Purine Nucleosides Using 8-Bromoguanosine as Precursor
Koh, Yung-Hyo,Landesman, Michael B.,Amador, Roberto,Rong, Frank,An, Haoyun,Hong, Zhi,Girardet, Jean-Luc
, p. 501 - 507 (2007/10/03)
A series of 2,6,8-trisubstituted purine nucleoside libraries was prepared by parallel solid-phase synthesis using 8-bromoguanosine as a common synthetic precursor. Polystyrene-methoxytrityl chloride resin was linked to the N 2 or O5′ position o
Efficient methods for the synthesis of [2-15N]guanosine and 2′-deoxy[2-15N]guanosine derivatives
Kamaike,Kinoshita,Niwa,Hirose,Suzuki,Ishido
, p. 59 - 75 (2007/10/03)
The nucleophilic addition-elimination reaction of 2′,3′, 5′-tri-O-acetyl-2-fluoro-O6-[2-(4-nitrophenyl)ethyl]inosine (8) with [15N]benzylamine in the presence of triethylamine afforded the N2-benzyl[2-15N]guanosine derivative (13) in a high yield, which was further convened into the N2-benzoyl[2-15N] guanosine derivative by treatment with ruthenium trichloride and tetrabutylammonium periodate. A similar sequence of reactions of 2′, 3′, 5′-tri-O-acetyl-2-fluoro-O6-[2-(methylthio)ethyl]inosine (9) and the 6-chloro-2-fluoro-9-(β-D-ribofuranosyl)-9H-purine derivative (11), which were respectively prepared from guanosine, with potassium [15N]phthalimide afforded the N2-phthaloyl [2-15N]guanosine derivative (15; 62%) and 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-6-chloro-2- [15N]phthalimido-9H-purine (17; 64%), respectively. Compounds 15 and 17 were then efficiently converted into 2′,3′,5′-tri-O-acetyl [2-15N]guanosine. The corresponding 2′-deoxy derivatives (16 and 18) were also synthesized through similar procedures.
Nucleosides. Part LIX. The 2-(4-nitrophenyl)ethylsulfonyl (Npes) group: A new type of protection in nucleoside chemistry
Pfister,Schirmeister,Mohr,Farkas,Stengele,Reiner,Dunkel,Gokhale,Charubala,Pfleiderer
, p. 1705 - 1737 (2007/10/02)
The 2-(4-nitrophenyl)ethylsulfonyl (npes) group is developed as a new sugar OH-blocking group in the ribonucleoside series. Its cleavage can be performed in a β-eliminating process under aprotic conditions using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the most effective base. Since sulfonates do not show acyl migration, partial protection of 1,2-cis-diol moieties is possible leading to new types of oligonucleotide building blocks. A series of Markiewicz-protected ribonucleosides 1-10 is converted into their 2'-O-[2-(4-nitrophenyl)ethylsulfonyl] derivatives 29-38 in which the 5'-O-Si bond can be cleaved by acid hydrolysis forming 39-45. Subsequent monomethoxytritylation leads to 46-50, and desilylation affords the 5'-O-(monomethoxytrityl)-2'-O-[2-(4-nitrophenyl)ethylsulfonyl]ribonucl eosides 51-55. Acid treatment to remove trityl groups do also not harm the npes group(→ 56-58). Unambiguous syntheses of fully blocked 2'-O-[2-(4-nitrophenyl)ethylsulfonyl]ribonucleosides 96-102 are achieved from the corresponding 3'-O-(tert-butyl)dimethylsilyl derivatives. Furthermore, various base-protected 5'-O-(monomethoxytrityl)- and 5'-O-(dimethoxytrityl)ribonucleosides, i.e. 59-77, are treated directly with 2-(4-nitrophenyl)ethylsulfonyl chloride forming in all cases a mixture of the 2',3'-di-O- and the two possible 2'- and 3'-O-monosulfonates 107-148 which can be separated into the pure components by chromatographic methods. The npes group is more labile towards DBU cleavage than the corresponding base-protecting 2-(4-nitrophenyl)ethyl (npe) and 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) groups allowing selective deblocking which is of great synthetic potential.
Nucleosides. Part LI. The 2-(4-Nitrophenyl)ethoxycarbonyl (npeoc) and 2-(2,4-Dinitrophenyl)ethoxycarbonyl (dnpeoc) Groups for Protection of Hydroxy Functions in Ribonucleosides and 2'-Deoxyribonucleosides
Schirmeister, Helga,Himmelsbach, Frank,Pfleiderer, Wolfgang
, p. 385 - 401 (2007/10/02)
The common 2'-deoxypyrimidine and -purine nucleosides, thymidine (4), O4-thymidine (17), 2'-deoxy-N4-cytidine (26), 2'-deoxy-N6-adenosine (39), and 2'-deoxy-N2--O6-guanosine (52) were further protected by the 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) and the 2-(2,4-dinitrophenyl)ethoxycarbonyl (dnpeoc) group at the OH functions of the sugar moiety to form new partially and fully blocked intermediates for nucleoside and nucleotide syntheses.The corresponding 5'-O-monomethoxytrityl derivatives 5, 18, 30, 40, and 56 were also used as starting material to synthesize some other intermediates which were not obtained by direct acylations.In the ribonucleoside series, the 5'-O-monomethoxytrityl derivatives 14, 36, 49, and 63 reacted with 2-(4-nitrophenyl)ethyl chloroformate (1) to the corresponding 2',3'-bis-carbonates 15, 37, 50, and 64 which were either detritylated to 16, 38, 51, and 65, respectively, or converted by 1,8-diazabicycloundec-7-ene (DBU) treatment to the 2',3'-cyclic carbonates 66-69.The newly synthesized compounds were characterized by elemental analyses and UV and 1H-NMR spectra.
