Chemical diversity of reagents that modify RNA 2'-OH in water: a review.

Electrophilic water-soluble compounds have proven versatile in reacting selectively with 2'-OH groups in RNA, enabling structure mapping, probing, caging, labeling, crosslinking, and conjugation of RNAs and in living cells. While early work focused on one or two types of reagents with limited properties, recent studies have greatly diversified the structure, properties, and applications of these reagents. Here we review the scope of documented RNA hydroxyl-reactive species reported to date, with an eye to the effects of chemical structure on reactivity with RNA and other useful properties. Multiple forms of carbonyl electrophiles are now known to react at the 2'-OH, and recently, sulfonyl and aryl electrophiles have also been documented to form bonds there in high yields as well. In addition to electrophilicity, data also point to significant effects of reagent stability, steric bulk, and chirality on reaction yields and selectivity. Finally, we outline reagent properties and principles that define utility in applications with RNA, with an eye to the design of future reagents.