Work

RNA 2′-OH modification with stable reagents enabled by nucleophilic catalysis

Year: 2025

Type: article

Abstract: RNA modification at 2'-OH has typically required highly reactive acylating species that exhibit short half-lives in water, challenging purification, and limiting shelf lives. Here, we investigate the use of more stable species as electrophilic reagents, employing nucleophilic catalysis to promote reactions. The results show that multiple previously unreported electrophiles can react in high stoichiometric yields with RNA under appropriate catalysis. Most notably, aryl esters can transfer acyl groups to RNA in one hour, but are stable for months even in pure water. The results expand the functional chemotypes of RNA-reactive species, and identify reagent classes with improved stability and selectivity.

Source: RSC Advances

DOI: 10.1039/d5ra06314k

Authors: Eric T. Kool, Sumon Pratihar, Pavitra S. Thacker, Dipanwita Banerjee, Moon Jung Kim, Ryuta Shioi

Institution: Stanford University

Language: English

Topic: Click Chemistry and Applications

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $1,042

Funders: National Institutes of Health, National Institute of General Medical Sciences, Fogarty International Center