- search hit 1 of 1
Ribozyme-catalyzed late-stage functionalization and fluorogenic labeling of RNA
Please always quote using this URN: urn:nbn:de:bvb:20-opus-327543
- 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 ringSite-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.…
Author: | Carolin P. M. Scheitl, Takumi Okuda, Juliane Adelmann, Claudia HöbartnerORCiD |
---|---|
URN: | urn:nbn:de:bvb:20-opus-327543 |
Document Type: | Journal article |
Faculties: | Fakultät für Chemie und Pharmazie / Institut für Organische Chemie |
Language: | English |
Parent Title (English): | Angewandte Chemie International Edition |
Year of Completion: | 2023 |
Volume: | 62 |
Article Number: | e202305463 |
Source: | Angewandte Chemie International Edition (2023) 62:e202305463 |
DOI: | https://doi.org/10.1002/anie.202305463 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Tag: | Aldehyde Bioconjugation; Bioorthogonal Tag; Fluorescence and Crosslinking; RNA Labelling; Ribozyme |
Release Date: | 2023/09/25 |
Licence (German): | CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International |