TY  - JOUR
A1  - Scheitl, Carolin P. M.
A1  - Okuda, Takumi
A1  - Adelmann, Juliane
A1  - Höbartner, Claudia
T1  - Ribozyme-catalyzed late-stage functionalization and fluorogenic labeling of RNA
JF  - Angewandte Chemie International Edition
N2  - Site-specific introduction of biorthogonal handles into RNAs is in high demand for decorating RNAs with fluorophores, affinity labels or other modifications. Aldehydes represent attractive functional groups for post-synthetic bioconjugation reactions. Here, we report a ribozyme-based method for the synthesis of aldehyde-functionalized RNA by directly converting a purine nucleobase. Using the methyltransferase ribozyme MTR1 as an alkyltransferase, the reaction is initiated by site-specific N1 benzylation of purine, followed by nucleophilic ring opening and spontaneous hydrolysis under mild conditions to yield a 5-amino-4-formylimidazole residue in good yields. The modified nucleotide is accessible to aldehyde-reactive probes, as demonstrated by the conjugation of biotin or fluorescent dyes to short synthetic RNAs and tRNA transcripts. Upon fluorogenic condensation with a 2,3,3-trimethylindole, a novel hemicyanine chromophore was generated directly on the RNA. This work expands the MTR1 ribozyme’s area of application from a methyltransferase to a tool for site-specific late-stage functionalization of RNA.
KW  - Aldehyde Bioconjugation
KW  - Bioorthogonal Tag
KW  - Fluorescence and Crosslinking
KW  - RNA Labelling
KW  - Ribozyme
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-327543
VL  - 62
ER  -