Mutually Orthogonal Bioconjugation of Vinyl Nucleosides for RNA Metabolic Labeling

We report a strategy for the orthogonal conjugation of the vinyl nucleosides, 5-vinyluridine (5-VU) and 2-vinyladenosine (2-VA), via selective reactivity with maleimide and tris(2-carboxyethyl)phosphine (TCEP), respectively. The orthogonality was investigated using density functional theory (DFT) and confirmed by reactions with vinyl nucleosides. Further, these chemistries were used to modify RNA for fluorescent cell imaging. These reactions allow for the expanded use of RNA metabolic labeling to study nascent RNA expression within different RNA populations.

Automated summary

This study reports a strategy for the orthogonal conjugation of vinyl nucleosides by selectively reacting with specific reagents, enabling the modification of RNA for fluorescent cell imaging. These reactions provide a new approach for studying nascent RNA expression within different RNA populations.