Synthesis of hairpin siRNA using 18β-glycyrrhetinic acid derivative as a loop motif

We synthesized a new phosphoramidite building block from 18β-glycyrrhetinic acid. This compound was introduced in the middle of the palindromic oligonucleotides and they formed hairpin structure. This 18β-glycyrrhetinic acid derivative excellently performed its role as hairpin loop. These hairpin ODNs had higher Tm values than the natural one and formed stable hairpin structure without any structural distortion. We found that stability of hairpin ODNs was changed according to the length of hairpin stem and modified hairpin ODNs, which had longer than seven base pair stem, were more stable than natural one based on Tm values. The shRNAs bearing similar modified loop were also synthesized. These modified shRNAs could suppress their target gene expression without losing their RNAi efficiency.