91592-85-7Relevant academic research and scientific papers
CYCLIC DINUCLEOTIDES AS ANTICANCER AGENTS
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Paragraph 1568; 1571; 1572, (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.
Nucleobase and ribose modifications control immunostimulation by a MicroRNA-122-mimetic RNA
Peacock, Hayden,Fucini, Raymond V.,Jayalath, Prasanna,Ibarra-Soza, Jose M.,Haringsma, Henry J.,Flanagan, W. Michael,Willingham, Aarron,Beal, Peter A.
, p. 9200 - 9203 (2011/08/04)
Immune stimulation is a significant hurdle in the development of effective and safe RNA interference therapeutics. Here, we address this problem in the context of a mimic of microRNA-122 by employing novel nucleobase and known 2′-ribose modifications. The
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
A chemical method for site-specific modification of RNA: The convertible nucleoside approach
Allerson, Charles R.,Chen, Swaine L.,Verdine, Gregory L.
, p. 7423 - 7433 (2007/10/03)
Knowledge of RNA structure can greatly facilitate the understanding of its biological function. However, the physical properties of RNA, especially its conformational heterogeneity, present an impediment to high-resolution structural analysis. Thus,lower resolution methods such as biochemical probing, phylogenetic analysis, and molecular modeling have come to serve an important role in RNA science. This situation has created the need for a means by which to constrain RNA structure, either to reduce its conformational flexibility or to help distinguish between alternative structural models. To address this need, we have developed chemistry that permits the site-specific introduction of functionalizable tethers into RNA. Here we report the design and synthesis of reagents for use in solid-phase RNA synthesis that allow the functionalization of the base moiety of C, C, and A residues. Upon incorporation into oligonucleotides and subsequent treatment with alkylamines, the convertible nucleoside derivatives reported here give rise to functionally tethered N4-alkyl-C, N6-alkyl-A, and N2-alkyl-G residues in RNA. The derivatized RNAs can then be used to target the attachment of chemical probes or the placement of disulfide cross-links as structural constraints. The attachment of nonnatural functional groups to RNA in this fashion provides a powerful means of both probing its structural environment and constraining its conformation. The size and functionality of the N-alkyl modification is determined solely by the choice of alkylamine, thereby permitting the preparation of a wide range of functionally tethered RNAs.
A convenient method for the preparation of N2,N2-dimethylguanosine
Avino,Mayordomo,Espuny,Bach,Eritja
, p. 1613 - 1617 (2007/10/02)
The preparation of N2,N2-dimethylguanosine is described. The use of the 2-(p-nitrophenyl)ethyl group instead of the benzyl protecting group for the O6 position of the guanine ring resulted in better yields and shorter protocols.
THE p-NITROPHENYLETHYL (NPE) GROUP. A VERSATILE NEW BLOCKING GROUP FOR PHOSPHATE AND AGLYCONE PROTECTION IN NUCLEOSIDES AND NUCLEOTIDES
Himmelsbach, Frank,Schulz, Bernd S.,Trichtinger, Thomas,Charubala, Ramamurthy,Pfleiderer, Wolfgang
, p. 59 - 72 (2007/10/02)
The syntheses of new monomeric building blocks for oligonucleotide synthesis via the phosphotriester approach containing the p-nitrophenylethyl group for phosphate and aglycone protection are described.Blocking of the amide function in guanosines at O6 can be achieved by the Mitsunobu reaction forming the corresponding O6-p-nitrophenylethyl derivatives (4,5,10).Sugar-protected thymidine (16) and uridine (17) have been alkylated at O4 in an SN1-type reaction by p-nitrophenylethyl iodide-silver carbonate in benzene to form the O4-p-nitrophenylethyl derivatives (18,19).Protection of the amino group in 2'-deoxycytidine (25) and cytidine (26) can be performed directly by 1-(p-nitrophenylethoxycarbonyl)-benzotriazole in DMF to obtain the corresponding carbamates (27,28) as a new type of N4-acylated cytidine derivative. p-Nitrophenylethoxycarbonylation of the amino group in 2'-deoxyadenosine (33) and adenosine (34) requires previous sugar protection by acyl or silyl groups and can then be achieved by p-nitrophenylethyl chloroformate or better by 1-methyl-3-p-nitrophenylethoxycarbonylimidazolium chloride to form N6-p-nitrophenylethoxycarbonyladenosines (38,39,40,42).The various p-nitrophenylethyl blocking groups are stable under mild hydrolytic conditions (e.g. ammonia and triethylamine) but can be cleaved selectively by DBU or DBN in aprotic solvents. 5'-O-Monomethoxytritylation (12,29,43) as well as phosphorylations at the 3'-OH group can be effected to give the corresponding 3'-(2,5-dichlorophenyl,p-nitrophenylethyl)-phosphotriesters (13,22,30,44) also in high yields.Oximate cleavage of the latter compounds to the phosphodiesters (14,24,32,46) and detritylation to the 5'-unblocked phosphotriesters (15,23,31,45) do not affect the aglycone protecting groups, thereby demonstrating their general versatility.The newly synthesized compounds have been characterized on the basis of their elementary analyses (C,N,H), and UV- and 1H-HMR-spectra.
SYNTHESIS OF O6-p-NITROPHENYLETHYL GUANOSINE AND 2'-DEOXYGUANOSINE DERIVATIVES
Trichtinger, Thomas,Charubala, Ramamurthy,Pfleiderer, Wolfgang
, p. 711 - 714 (2007/10/02)
The p-nitrophenylethyl group is introduced into the O6-position of 2'-deoxyguanosine and guanosine via the Mitsunobu-reaction to yield valuable building blocks for oligonucleotide syntheses.
