- SYNTHESIS AND STRUCTURE OF HIGH POTENCY RNA THERAPEUTICS
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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.
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- A prebiotically plausible synthesis of pyrimidine β-ribonucleosides and their phosphate derivatives involving photoanomerization
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Previous research has identified ribose aminooxazoline as a potential intermediate in the prebiotic synthesis of the pyrimidine nucleotides with remarkable properties. It crystallizes spontaneously from reaction mixtures, with an enhanced enantiomeric excess if initially enantioenriched, which suggests that reservoirs of this compound might have accumulated on the early Earth in an optically pure form. Ribose aminooxazoline can be converted efficiently into α-ribocytidine by way of 2,2'-anhydroribocytidine, although anomerization to β-ribocytidine by ultraviolet irradiation is extremely inefficient. Our previous work demonstrated the synthesis of pyrimidine β-ribonucleotides, but at the cost of ignoring ribose aminooxazoline, using arabinose aminooxazoline instead. Here we describe a long-sought route through ribose aminooxazoline to the pyrimidine β-ribonucleosides and their phosphate derivatives that involves an extraordinarily efficient photoanomerization of α-2-thioribocytidine. In addition to the canonical nucleosides, our synthesis accesses β-2-thioribouridine, a modified nucleoside found in transfer RNA that enables both faster and more-accurate nucleic acid template-copying chemistry.
- Xu, Jianfeng,Tsanakopoulou, Maria,Magnani, Christopher J.,Szabla, Rafa?,?poner, Judit E.,?poner, Ji?í,Góra, Robert W.,Sutherland, John D.
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p. 303 - 309
(2017/04/03)
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- Straightforward pyrimidine ring construction: A versatile tool for the synthesis of nucleobase and nucleoside analogues
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A general route to 1,2,4-trisubstituted pyrimidines is described in one to three steps from a common key precursor, diazadienium iodide 2. An efficient preliminary [4+2] cyclocondensation reaction between the azabutadiene building block 2 and various iso(thio)cyanates constitutes an original construction of the pyrimidine skeleton. Subsequent structural modifications on the heterocycle allow the elaboration of a 1-substituted pyrimidine library that includes nucleoside analogues. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Robin, Aelig,Julienne, Karine,Meslin, Jean-Claude,Deniaud, David
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p. 634 - 643
(2007/10/03)
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