201667-28-9Relevant academic research and scientific papers
Synthesis of Adenine Dinucleosides 2′,5′-Bridged by Sulfur-Containing Linkers as Bisubstrate SAM Analogues for Viral RNA 2′-O-Methyltransferases
Ahmed-Belkacem, Rostom,Ortiz, Priscila Sutto,Decroly, Etienne,Vasseur, Jean-Jacques,Debart, Fran?oise
, p. 6486 - 6495 (2019)
Viral RNA 2′-O-methyltransferases play a crucial role for luring the host cell innate antiviral response during a viral infection by catalyzing either the methylation of the 5′-end RNA cap-structure at 2′-OH of nucleoside N1 or by inducing internal 2′-O-methylation of adenosines within RNA sequence using S-adenosyl-l-methionine (SAM) as the methyl donor. Our goal is to synthesize bisubstrate SAM analogues mimicking the transition state of the 2′-O-methylation of the RNA in order to block viral 2′-O-methyltransferases and struggle against emerging viruses. Here we designed and synthesized five dinucleosides by connecting a 5′-thioadenosine representing the SAM to the 2′-OH of another adenosine unit mimicking the RNA substrate, via various sized sulfur-containing linkers such as alkylthioether linkers, sulfoxide or sulfone derivatives, or a disulfide bond.
The 2-cyano-2,2-dimethylethanimine-N-oxymethyl group for the 2′-hydroxyl protection of ribonucleosides in the solid-phase synthesis of RNA sequences
Cie?lak, Jacek,Ausín, Cristina,Grajkowski, Andrzej,Beaucage, Serge L.
, p. 4623 - 4632 (2013/04/24)
The reaction of 2-cyano-2-methyl propanal with 2′-O- aminooxymethylribonucleosides leads to stable and yet reversible 2′-O-(2-cyano-2,2-dimethylethanimine-N-oxymethyl)ribonucleosides. Following N-protection of the nucleobases, 5′-dimethoxytritylation and 3′-phosphitylation, the resulting 2′-protected ribonucleoside phosphoramidite monomers are employed in the solid-phase synthesis of three chimeric RNA sequences, each differing in their ratios of purine/pyrimidine. When the activation of phosphoramidite monomers is performed in the presence of 5-benzylthio-1H-tetrazole, coupling efficiencies averaging 99 % are obtained within 180 s. Upon completion of the RNA-chain assemblies, removal of the nucleobase and phosphate protecting groups and release of the sequences from the solid support are carried out under standard basic conditions, whereas the cleavage of 2′-O-(2-cyano-2,2-dimethylethanimine-N-oxymethyl) protective groups is effected (without releasing RNA alkylating side-products) by treatment with tetra-n-butylammonium fluoride (0.5 m) in dry DMSO over a period of 24-48 h at 55 °C. Characterization of the fully deprotected RNA sequences by polyacrylamide gel electrophoresis (PAGE), enzymatic hydrolysis, and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry confirmed the identity and quality of these sequences. Thus, the use of 2′-O-aminooxymethylribonucleosides in the design of new 2′-hydroxyl protecting groups is a powerful approach to the development of a straightforward, efficient, and cost-effective method for the chemical synthesis of high-quality RNA sequences in the framework of RNA interference applications. Copyright
An azidomethyl protective group in the synthesis of oligoribonucleotides by the phosphotriester method
Efimov,Aralov,Fedunin,Klykov,Chakhmakhcheva
scheme or table, p. 250 - 253 (2010/04/06)
A rapid and effective method of an automatic oligoribonucleotide synthesis alternative to the phosphoramidite one was developed. This method is based on the phosphotriester approach to internucleotide bond formation under intramolecular O-nucleophilic cat
2'-O-methylthiomethyl modifications in hammerhead ribozymes
Karpeisky, Alexander,Gonzalez, Carolyn,Burgin, Alex B.,Usman, Nassim,Beigelman, Leonid
, p. 955 - 958 (2007/10/03)
The synthesis of all four phosphoramidites of 2'-O-methylthiomethyl ribonucleosides and their incorporation into hammerhead ribozymes and influence on nuclease stability and catalytic activity is described.
