Synthesis and Biophysical Properties of Phosphorodiamidate Piperidino Oligomers

We report the synthesis of piperidino nucleoside phosphoramidates functionalized with uracil, cytosine, guanine, and adenine and their incorporation into oligomers. High-performance liquid chromatography analyses demonstrated that a phosphorodiamidate piperidino oligomer (PPO) is more lipophilic than a phosphorodiamidate morpholino oligomer (PMO) of the same tetrameric sequence. A PMO containing piperidino residues formed duplexes with both DNA and RNA, and the PPO had higher stability at endosomolytic pH and higher hydrophobicity than the PMO.

Automated summary

We synthesized piperidino nucleoside phosphoramidates functionalized with uracil, cytosine, guanine, and adenine and incorporated them into oligomers. High-performance liquid chromatography analyses showed that a phosphorodiamidate piperidino oligomer (PPO) is more lipophilic than a phosphorodiamidate morpholino oligomer (PMO) with the same tetrameric sequence. The PMO containing piperidino residues formed duplexes with both DNA and RNA, while the PPO exhibited higher stability at endosomolytic pH and higher hydrophobicity than the PMO.