2'-amino-modified ribonucleotides as probes for local interactions within RNA

The 2'-hydroxyl group plays an integral role in RNA structure and catalysis. This ubiquitous component of the RNA backbone can participate in multiple interactions essential for RNA function, such as hydrogen bonding and metal ion coordination, but the multifunctional nature of the 2'-hydroxyl renders identification of these interactions a significant challenge. By virtue of their versatile physicochemical properties, such as distinct metal coordination preferences, hydrogen bonding properties, and ability to be protonated, 2'-amino-2'-deoxyribonucleotides can serve as tools for probing local interactions involving 2'-hydroxyl groups within RNA. The 2'-amino group can also serve as a chemoselective site for covalent modification, permitting the introduction of probes for investigation of RNA structure and dynamics. In this chapter, we describe the use of 2'-aminonucleotides for investigation of local interactions within RNA, focusing on interactions involving 2'-hydroxyl groups required for RNA structure, function, and catalysis.