A method for the synthesis of chimeric oligonucleotides was developed to incorporate purine nucleobases and multiple triazole linkers in natural, phosphate-linked structures of RNA. A solution-phase synthesis method for triazole-linked RNA oligomers via copper-catalyzed azide-alkyne cycloaddition reaction was optimized and tolerated purine nucleobases and protecting groups for further transformations. Three TLRNA trinucleotides with 5′-protected hydroxy and 3′-phosphoramidite groups were prepared, and one congener with a representative sequence was subjected to automated, solid-phase phosphoramidite synthesis. The synthesis allowed the efficient preparation of 13-mer chimeric RNA oligonucleotides with two triazole linkers, ten phosphate linkers and purine/pyrimidine nucleobases. The chimeric oligonucleotide was found applicable to a cell-free translation system as mRNA and provided the genetic code for dipeptide production.
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