Water-Soluble Leaving Group Enables Hydrophobic Functionalization of RNA.

Attachment of hydrophobic groups to RNA is challenging because of their poor aqueous solubility. One-step acylation of RNA 2'-OH groups in water using a water-soluble imidazole leaving group is described. The effect of the hydrophobic groups on hybridization is reported. Furthermore, propargyl-functionalized RNA is shown to be readily labeled with a fluorophore. Lastly, heptyl-functionalized RNA is found to exhibit the unusual property of solubility in organic solvents.