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Synthesis of oxytocin derivatives lipidated via a carbonate or carbamate linkage as a long-acting therapeutic agent for social impairment-like behaviors
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| Title: | Synthesis of oxytocin derivatives lipidated via a carbonate or carbamate linkage as a long-acting therapeutic agent for social impairment-like behaviors |
| Authors: | Cherepanov, Stanislav M. Browse this author | | Miura, Risako Browse this author | | Shabalova, Anna A. Browse this author | | Ichinose, Wataru Browse this author | | Yokoyama, Shigeru Browse this author | | Fukuda, Hayato Browse this author | | Watanabe, Mizuki Browse this author →KAKEN DB | | Higashida, Haruhiro Browse this author | | Shuto, Satoshi Browse this author →KAKEN DB |
| Keywords: | Lipidation | | Long-acting | | Oxytocin | | Social impairment-like behavior | | Prodrug |
| Issue Date: | 1-Aug-2019 |
| Publisher: | Elsevier |
| Journal Title: | Bioorganic & Medicinal Chemistry / Bioorganic and Medicinal Chemistry |
| Volume: | 27 |
| Issue: | 15 |
| Start Page: | 3358 |
| End Page: | 3363 |
| Publisher DOI: | 10.1016/j.bmc.2019.06.018 |
| Abstract: | In the course of our studies of hydrophobic oxytocin (OT) analogues, we newly synthesized lipidated OT (LOT-4a-c and LOT-5a-c), in which a long alkyl chain (C14-C16) is conjugated via a carbonate or carbamate linkage at the Tyr-2 phenolic hydroxy group and a palmitoyl group at the terminal amino group of Cys-1. These LOTs did not activate OT and vasopressin receptors. Among the LOTs, however, LOT-4c, having a C16-chain via a carbonate linkage at the phenolic hydroxyl group of the Tyr-2, showed very long-lasting action for the recovery of impaired social behavior in CD38 knockout mice, a rodent model of autistic phenotypes, whereas the effect of OT itself rapidly diminished. These results indicate that LOT-4c may serve as a potential prodrug in mice. |
| Rights: | © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/82355 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 周東 智
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