Author:
Tsurusaki Taiki,Sato Kazuki,Imai Hiroki,Hirai Kunihiro,Takahashi Daisuke,Wada Takeshi
Abstract
AbstractPhosphorodiamidate morpholino oligonucleotides (PMOs) are a promising type of antisense oligonucleotides, but their challenging synthesis makes them difficult to access. This research presents an efficient synthetic approach for PMOs using the H-phosphonate approach. The use of phosphonium-type condensing reagents significantly reduced coupling times compared with the current synthetic approach. Furthermore, phosphonium-type condensing reagents facilitated the fragment condensation of PMO, synthesizing up to 8-mer containing all four nucleobases with remarkable coupling efficacy. This is the first report on the convergent synthesis of PMOs. This approach would facilitate the large-scale synthesis of PMOs and accelerate their popularity and accessibility as a next-generation therapy.
Funder
Japan Science and Technology Agency
Japan Agency for Medical Research and Development
Publisher
Springer Science and Business Media LLC