Convergent synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) by the H-phosphonate approach
Abstract Phosphorodiamidate 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-...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-38698-2 |
| _version_ | 1797576709168431104 |
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| author | Taiki Tsurusaki Kazuki Sato Hiroki Imai Kunihiro Hirai Daisuke Takahashi Takeshi Wada |
| author_facet | Taiki Tsurusaki Kazuki Sato Hiroki Imai Kunihiro Hirai Daisuke Takahashi Takeshi Wada |
| author_sort | Taiki Tsurusaki |
| collection | DOAJ |
| description | Abstract Phosphorodiamidate 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. |
| first_indexed | 2024-03-10T21:56:37Z |
| format | Article |
| id | doaj.art-81ea6cf1ee5040e495a01ef4552d0d10 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T21:56:37Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-81ea6cf1ee5040e495a01ef4552d0d102023-11-19T13:05:58ZengNature PortfolioScientific Reports2045-23222023-08-0113111010.1038/s41598-023-38698-2Convergent synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) by the H-phosphonate approachTaiki Tsurusaki0Kazuki Sato1Hiroki Imai2Kunihiro Hirai3Daisuke Takahashi4Takeshi Wada5Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceDepartment of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceDepartment of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceResearch Institute for Bioscience Products and Fine Chemicals, Ajinomoto Co., Inc.Research Institute for Bioscience Products and Fine Chemicals, Ajinomoto Co., Inc.Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of ScienceAbstract Phosphorodiamidate 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.https://doi.org/10.1038/s41598-023-38698-2 |
| spellingShingle | Taiki Tsurusaki Kazuki Sato Hiroki Imai Kunihiro Hirai Daisuke Takahashi Takeshi Wada Convergent synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) by the H-phosphonate approach Scientific Reports |
| title | Convergent synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) by the H-phosphonate approach |
| title_full | Convergent synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) by the H-phosphonate approach |
| title_fullStr | Convergent synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) by the H-phosphonate approach |
| title_full_unstemmed | Convergent synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) by the H-phosphonate approach |
| title_short | Convergent synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) by the H-phosphonate approach |
| title_sort | convergent synthesis of phosphorodiamidate morpholino oligonucleotides pmos by the h phosphonate approach |
| url | https://doi.org/10.1038/s41598-023-38698-2 |
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