Abstract
The chemical synthesis of modified oligoribonucleotides represents a powerful approach to study the structure, stability, and biological activity of RNAs. Selected RNA modifications have been proven to enhance the drug-like properties of RNA oligomers providing the oligonucleotide-based therapeutic agents in the antisense and siRNA technologies. The important sites of RNA modification/functionalization are the nucleobase residues. Standard phosphoramidite RNA chemistry allows the site-specific incorporation of a large number of functional groups to the nucleobase structure if the building blocks are synthetically obtainable and stable under the conditions of oligonucleotide chemistry and work-up. Otherwise, the chemically modified RNAs are produced by post-synthetic oligoribonucleotide functionalization. This review highlights the post-synthetic RNA modification approach as a convenient and valuable method to introduce a wide variety of nucleobase modifications, including recently discovered native hypermodified functional groups, fluorescent dyes, photoreactive groups, disulfide crosslinks, and nitroxide spin labels.
Highlights
A significant interest has been observed in the use of modified oligoribonucleotides in the fields of molecular biology, biochemistry, and medicine [1,2,3]
Among 150 modified nucleosides identified in cellular RNA sequences, more than 95% of functional groups are installed in the nucleobase heterocycles (Figure 1) [4,5]
Pd-catalyzed cross-coupling a column [79], as standard protocol of the post-synthetic approach, whichreactions involvesare theperformed full-lengthonoligonucleotide after the incorporation of iodonucleoside phophoramidite. It means that the synthesis substrate, the Sonogashira Pd-catalyzed cross-coupling reactions are performed onis ainterrupted column [79], after iodonucleoside insertion, and the column is after the incorporation of iodonucleoside phophoramidite
Summary
A significant interest has been observed in the use of modified oligoribonucleotides in the fields of molecular biology, biochemistry, and medicine [1,2,3]. A post-synthetic modification approach based on selective chemical of a modified phosphoramidite building block and its subsequent incorporation into the RNA chain; of precursor unit(s) in the full-length oligonucleotide prepared by thereaction(s) classical method. This review for the first time summarizes the methods of site-specific incorporation of nucleobase functionalization due to the high abundance of nucleobase modifications in the nature nucleobase-modified units into RNA oligomers via the post-synthetic strategy. We focused on and the high convenience of the post-synthetic strategy to construct the nucleobase-labeled chemical the nucleobase functionalization due to the high abundance of nucleobase modifications in the nature or biophysical probes. The scope of post-synthetically reactive precursor oligonucleotides has been andlimited the high convenience ofprepared the post-synthetic strategy to construct theTo nucleobase-labeled chemical to RNA oligomers by the phosphoramidite chemistry. Post-synthetic methods best suited to the assumed chemical–biological objectives, a large number of
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