bc0c00024_si_001.pdf (1.13 MB)
Innately Water-Soluble Isatoic Anhydrides with Modulated Reactivities for RNA SHAPE Analysis
journal contribution
posted on 2020-02-17, 05:32 authored by Adam B. Fessler, Abhishek Dey, Dominic S. Finis, Anthony J. Fowler, Kausik Chakrabarti, Craig A. Ogle1-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.