55486-09-4Relevant academic research and scientific papers
SYNTHESIS AND STRUCTURE OF HIGH POTENCY RNA THERAPEUTICS
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, (2019/01/15)
This invention provides expressible polynucleotides, which can express a target protein or polypeptide. Synthetic mRNA constructs for producing a protein or polypeptide can contain one or more 5′ UTRs, where a 5′ UTR may be expressed by a gene of a plant. In some embodiments, a 5′ UTR may be expressed by a gene of a member of Arabidopsis genus. The synthetic mRNA constructs can be used as pharmaceutical agents for expressing a target protein or polypeptide in vivo.
2′-: O -Methyl- and 2′- O -propargyl-5-methylisocytidine: Synthesis, properties and impact on the isoCd-dG and the isoCd-isoGd base pairing in nucleic acids with parallel and antiparallel strand orientation
Jana, Sunit K.,Leonard, Peter,Ingale, Sachin A.,Seela, Frank
, p. 4927 - 4942 (2016/06/13)
Oligonucleotides containing 2′-O-methylated 5-methylisocytidine (3) and 2′-O-propargyl-5-methylisocytidine (4) as well as the non-functionalized 5-methyl-2′-deoxyisocytidine (1b) were synthesized. MALDI-TOF mass spectra of oligonucleotides containing 1b are susceptible to a stepwise depyrimidination. In contrast, oligonucleotides incorporating 2′-O-alkylated nucleosides 3 and 4 are stable. This is supported by acid catalyzed hydrolysis experiments performed on nucleosides in solution. 2′-O-Alkylated nucleoside 3 was synthesized from 2′-O-5-dimethyluridine via tosylation, anhydro nucleoside formation and ring opening. The corresponding 4 was obtained by direct regioselective alkylation of 5-methylisocytidine (1d) with propargyl bromide under phase-transfer conditions. Both compounds were converted to phosphoramidites and employed in solid-phase oligonucleotide synthesis. Hybridization experiments resulted in duplexes with antiparallel or parallel chains. In parallel duplexes, methylation or propargylation of the 2′-hydroxyl group of isocytidine leads to destabilization while in antiparallel DNA this effect is less pronounced. 2′-O-Propargylated 4 was used to cross-link nucleosides and oligonucleotides to homodimers by a stepwise click ligation with a bifunctional azide.
Sugar conformational effects on the photochemistry of thymidylyl(3′-5′)thymidine
Ostrowski, Tomasz,Maurizot, Jean-Claude,Adeline, Marie-Therese,Fourrey, Jean-Louis,Clivio, Pascale
, p. 6502 - 6510 (2007/10/03)
The synthesis and conformational analysis of 2′-O,5-dimethyluridylyl(3′-5′)-2′-O,5-dimethyluridine (1a), the analogue of thymidylyl(3′-5′)thymidine (TpT; 1b) in which a methoxy group replaces each 2′-α-hydrogen atom, are described. In comparison with TpT, such modification increases the population of the C3′-endo conformer of the sugar ring puckering at the 5′- and 3′-ends from 30 to 75% and from 37 to 66%, respectively. Photolyses of 1a and TpT at 254 nm are qualitatively comparable (the cis-syn cyclobutane pyrimidine dimer and the (6-4) photoproduct are formed), although it is significantly faster in the case of 1a. These results are explained by the increased propensity of the modified dinucleotide to adopt a base-stacked conformation geometry reminiscent of that for TpT.
Synthesis of amide-linked [(3')CH2CO-NH(5')] nucleoside analogues of small oligonucleotides
Robins, Morris J.,Doboszewski, Bogdan,Nilsson, Bradley L.,Peterson, Matt A.
, p. 69 - 86 (2007/10/03)
We report syntheses of new amide-linked (di-penta)nucleoside analogues of antisense oligonucleotide components. Solution-phase coupling of 3'- (carboxymethyl)-3'-deoxy- and 5'-amino-5'-deoxynucleoside derivatives provides amide dimers. Activated [3'-(carboxymethyl)-3'-deoxy] units with a 5'-azido-5'-deoxy function provide 'masked' 5'-amino-5'-deoxy residues for chain extension, and a 5'-O-DMT-protected unit provides the 5'-terminus for attachment to a phosphodiester linkage.
A novel and economical synthesis of 2′-o-alkyl-uridines
Ross, Bruce S.,Springer, Robert H.,Tortorici, Zeb,Dimock, Stuart
, p. 1641 - 1643 (2007/10/03)
A highly efficient, two-step method to make 2′-O-methyluridine is described using only inexpensive reagents and no chromatography. The method is applicable for some other alkyls as well as some other pyrimidine derivatives. Copyright
Apparatus and processes for the large scale generation and transfer of diazomethane
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, (2008/06/13)
For large scale preparation of pyrimidine ribonucleosides, the intermediate 2-O-methyl-(or ethyl)-1,3,5-tri-O-benzoyl-α-D-ribose can be prepared using a diazomethane (or diazoethane) reaction that is controlled via an inert solvent transferring system. This transfer system allows for large scale preparations of the pyrimidine ribonucleosides.
38. A new access to 2'-O-alkylated ribonucleosides and properties of 2'-O-alkylated oligoribonucleotides
Martin
, p. 486 - 504 (2007/10/02)
A general access to 2'-O-alkylated ribonucleosides using the key intermediate 5 is presented. The incorporation of 2'-O-'ethyleneglycol'- and 2'-O-'glycerol'-substituted (i.e., 2'-O-(2-hydroxyethyl)- and 2'-O-(2,3-dihydroxypropyl)-substituted) ribonucleosides into oligonucleotides affords a new generation of oligonucleotides with high affinity for RNA, high specificity, and increased nuclease resistance.
General preparative synthesis of 2'-O-methylpyrimidine ribonucleosides
Ross,Springer,Vasquez,Andrews,Cook,Acevedo
, p. 765 - 769 (2007/10/02)
A convergent and general approach to synthesizing 2'-O-methylpyrimidine ribonucleosides 4a-e-, 6, 7 on a multigram scale is described which begins with an improved procedure for making larger quantities of 2-O-methyl-1,3,5-tri-O-benzoyl-α-D-ribose. The sugar was reacted with the desired silylated pyrimidines at room temperature under Vorbruggen conditions. The crude products contained less than 10% of the α anomers and the desired β anomers were isolated by crystallization. The blocked nucleosides were then deprotected and isolated by standard methods.
2'-O,5-dimethyluridine: A total synthesis and single crystal X-ray diffraction study
Lewis,Revankar,Hogan
, p. 1309 - 1316 (2007/10/02)
A new method for the synthesis of 2'-O,5-dimethyluridine (5) has provided the title compound in a higher yield. Application of a one-pot ribosylation methodology resulted in an efficient, high yield synthesis of 5-methyluridine (ribothymine, 3b). An X-ray diffraction analysis of 5 disclosed the conformation of the sugar moiety of this nucleoside as anti, N(3'-endo), g+.
