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Updated: Dec 28, 2025

Using In Vitro and In-cell SHAPE to Investigate Small Molecule Induced Pre-mRNA Structural Changes
Published on: January 30, 2019
Innately Water-Soluble Isatoic Anhydrides with Modulated Reactivities for RNA SHAPE Analysis
Adam B Fessler, Abhishek Dey, Dominic S Finis
1NuChemie, LLC, Charlotte, North Carolina 28227, United States.
Abstract:
1-Methyl-7-nitroisatoic anhydride (1M7) and 2-methylnicotinic acid imidazolide (NAI) are two of the most commonly applied RNA-SHAPE electrophiles; 1M7 due to its high reactivity and NAI for its solubility and cell permeability. While the addition of a nitro group yields desirable activation of the reagent, it also leads to poorer water solubility. This limited solubility has motivated the development of water-soluble reagents. We present alternative, isatoic anhydride-based reagents possessing variable reactivities that are simultaneously water-soluble. Solubility is gained by using a quaternary ammonium, while modulation of the reactivity is obtained by functionalization of the aryl ring. The syntheses of the reagents are discussed, and the electrophiles are demonstrated to be suitable for use for an in vitro RNA SHAPE experiment when directly compared to 1M7.
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