Ribozyme-catalyzed late-stage functionalization and fluorogenic labeling of RNA
Zitieren Sie bitte immer diese 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.…
Autor(en): | Carolin P. M. Scheitl, Takumi Okuda, Juliane Adelmann, Claudia HöbartnerORCiD |
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URN: | urn:nbn:de:bvb:20-opus-327543 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Fakultät für Chemie und Pharmazie / Institut für Organische Chemie |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Angewandte Chemie International Edition |
Erscheinungsjahr: | 2023 |
Band / Jahrgang: | 62 |
Aufsatznummer: | e202305463 |
Originalveröffentlichung / Quelle: | Angewandte Chemie International Edition (2023) 62:e202305463 |
DOI: | https://doi.org/10.1002/anie.202305463 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Freie Schlagwort(e): | Aldehyde Bioconjugation; Bioorthogonal Tag; Fluorescence and Crosslinking; RNA Labelling; Ribozyme |
Datum der Freischaltung: | 25.09.2023 |
Lizenz (Deutsch): | CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International |