Phosphine-Mediated Bioconjugation of the 3′-End of RNA

Staudinger ligation is an attractive
bio-orthogonal reaction that
has been widely used to tag proteins, carbohydrates, and nucleic acids.
Here, we explore the traceless variant of the Staudinger ligation
for 3′-end modification of oligoribonucleotides. An azido-containing
dinucleotide was used to study the ligation. Nine phosphines containing
reactive groups, affinity purification tags, or photoswitch probes
have been successfully obtained. The corresponding modified dinucleotides
were synthesized and characterized by LC/MS. Mechanistic interpretations
of the reaction are proposed, in particular, the unprecedented formation
of an oxazaphospholane nucleotide derivative, which was favored by
the vicinal position of 2′-N3 and 3′-OH functional
groups on the terminal ribose has been observed. The post-functionalization
of a 24-nt RNA with a photoactivable tag is also reported.