Synthesis of RNA 5′-Azides from 2′-O-Pivaloyloxymethyl-Protected RNAs and Their Reactivity in Azide–Alkyne Cycloaddition Reactions

Commercially available 2′-O-pivaloyloxymethyl (PivOM) phosphoramidites were employed in an SPS protocol for RNA 5′ azides. The utility of the N3-RNAs in CuAAC and SPAAC was demonstrated by RNA 5′ labeling, chemical ligation including fragment joining and cyclization, and bioconjugation. As a result, several new RNA conjugates that may be valuable tools for studies on biological events such as innate immune response (cyclic dinucleotides), post-transcriptional gene regulation (circular RNAs), or mRNA turnover (m7G capped RNAs) were obtained.