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Ring Expansion Leads to a More Potent Analogue of Ipomoeassin F
[Image: see text] Two new ring-size-varying analogues (2 and 3) of ipomoeassin F were synthesized and evaluated. Improved cytotoxicity (IC(50): from 1.8 nM) and in vitro protein translocation inhibition (IC(50): 35 nM) derived from ring expansion imply that the binding pocket of Sec61α (isoform 1) c...
| Autores principales: | , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical
Society
2020
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808706/ https://www.ncbi.nlm.nih.gov/pubmed/33264019 http://dx.doi.org/10.1021/acs.joc.0c01659 |
| _version_ | 1783636958627495936 |
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| author | Zong, Guanghui Hu, Zhijian Duah, Kwabena Baffour Andrews, Lauren E. Zhou, Jianhong O’Keefe, Sarah Whisenhunt, Lucas Shim, Joong Sup Du, Yuchun High, Stephen Shi, Wei Q. |
| author_facet | Zong, Guanghui Hu, Zhijian Duah, Kwabena Baffour Andrews, Lauren E. Zhou, Jianhong O’Keefe, Sarah Whisenhunt, Lucas Shim, Joong Sup Du, Yuchun High, Stephen Shi, Wei Q. |
| author_sort | Zong, Guanghui |
| collection | PubMed |
| description | [Image: see text] Two new ring-size-varying analogues (2 and 3) of ipomoeassin F were synthesized and evaluated. Improved cytotoxicity (IC(50): from 1.8 nM) and in vitro protein translocation inhibition (IC(50): 35 nM) derived from ring expansion imply that the binding pocket of Sec61α (isoform 1) can accommodate further structural modifications, likely in the fatty acid portion. Streamlined preparation of the key diol intermediate 5 enabled gram-scale production, allowing us to establish that ipomoeassin F is biologically active in vivo (MTD: ∼3 mg/kg). |
| format | Online Article Text |
| id | pubmed-7808706 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| publisher | American Chemical
Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-78087062021-01-15 Ring Expansion Leads to a More Potent Analogue of Ipomoeassin F Zong, Guanghui Hu, Zhijian Duah, Kwabena Baffour Andrews, Lauren E. Zhou, Jianhong O’Keefe, Sarah Whisenhunt, Lucas Shim, Joong Sup Du, Yuchun High, Stephen Shi, Wei Q. J Org Chem [Image: see text] Two new ring-size-varying analogues (2 and 3) of ipomoeassin F were synthesized and evaluated. Improved cytotoxicity (IC(50): from 1.8 nM) and in vitro protein translocation inhibition (IC(50): 35 nM) derived from ring expansion imply that the binding pocket of Sec61α (isoform 1) can accommodate further structural modifications, likely in the fatty acid portion. Streamlined preparation of the key diol intermediate 5 enabled gram-scale production, allowing us to establish that ipomoeassin F is biologically active in vivo (MTD: ∼3 mg/kg). American Chemical Society 2020-12-02 2020-12-18 /pmc/articles/PMC7808706/ /pubmed/33264019 http://dx.doi.org/10.1021/acs.joc.0c01659 Text en © 2020 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
| spellingShingle | Zong, Guanghui Hu, Zhijian Duah, Kwabena Baffour Andrews, Lauren E. Zhou, Jianhong O’Keefe, Sarah Whisenhunt, Lucas Shim, Joong Sup Du, Yuchun High, Stephen Shi, Wei Q. Ring Expansion Leads to a More Potent Analogue of Ipomoeassin F |
| title | Ring Expansion Leads
to a More Potent Analogue of
Ipomoeassin F |
| title_full | Ring Expansion Leads
to a More Potent Analogue of
Ipomoeassin F |
| title_fullStr | Ring Expansion Leads
to a More Potent Analogue of
Ipomoeassin F |
| title_full_unstemmed | Ring Expansion Leads
to a More Potent Analogue of
Ipomoeassin F |
| title_short | Ring Expansion Leads
to a More Potent Analogue of
Ipomoeassin F |
| title_sort | ring expansion leads
to a more potent analogue of
ipomoeassin f |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808706/ https://www.ncbi.nlm.nih.gov/pubmed/33264019 http://dx.doi.org/10.1021/acs.joc.0c01659 |
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