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Covalent Chemical 5'-Functionalization of RNA with Diazo Reagents

Gampe, Christian and Hollis-Symynkywicz, Micah and Zecri, Frederic (2016) Covalent Chemical 5'-Functionalization of RNA with Diazo Reagents. Angewandte Chemie. International edition, 55 (35). pp. 10283-10286. ISSN 14337851

Abstract

Functionalization of RNA at the 5’-terminus is important for analytical and therapeutic purposes. Currently, these RNAs are engineered de novo starting with a chemically functionalized 5’-nucleotide, which is incorporated into RNA using chemical synthesis or biochemical techniques. Methods for direct chemical modification of native RNA would provide an attractive alternative but are currently underexplored. Here we report that diazo compounds can be used to selectively alkylate the 5’-phosphate of ribo(oligo)nucleotides to give RNA labeled via a native phosphate ester bond. We applied this method to functionalize an oligonucleotide with an orthosteric inhibitor of the eukaryotic initiation factor 4E (eIF4E), an enzyme involved in mRNA recognition. The modified RNA binds to eIF4E, demonstrating the utility of this labelling technique to modulate biological activity of RNA. This method complements existing techniques and may be used to chemically introduce a broad range of functional handles at the 5’-end of RNA.

Item Type: Article
Date Deposited: 09 Nov 2016 00:45
Last Modified: 09 Nov 2016 00:45
URI: https://oak.novartis.com/id/eprint/28305

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