Hydrolysis of Phosphodiester Bonds within RNA Hairpin Loops in Buffer Solutions: the Effect of Secondary Structure on the Inherent Reactivity of RNA Phosphodiester Bonds

The hydrolysis of phosphodiester bonds of chimeric 2′-O-methyloligoribonucleotides was studied in buffer solutions. Pseudo-first-order rate constants for cleavage of phosphodiester bonds within hairpin loops were calculated and compared with those for cleavage of phosphodiester bonds within double-stranded stems and linear single-stranded oligonucleotides. No large differences in reactivity were observed: some of the hairpin structures studied were slightly less and others slightly more reactive than the linear reference. These results suggest that phosphodiester bonds within small hairpin loops are conformationally free to cleave by an in-line mechanism, but also that the secondary structure may influence the reactivity of phosphodiester bonds.