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We present a chemo-enzymatic approach for site-specific labeling of 5'-capped RNAs based on bioorthogonal chemistry. A trimethylguanosine synthase was engineered to transfer a terminal azido moiety to the 5'-cap which could be further modified using strain-promoted azide-alkyne cycloaddition (SPAAC).

Bioorthogonal site-specific labeling of the 5′-cap structure in eukaryotic mRNAs