A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain
© 2020 American Chemical Society. Effective delivery to the brain limits the development of novel glioblastoma therapies. Here, we introduce conjugation between platinum(IV) prodrugs of cisplatin and perfluoroaryl peptide macrocycles to increase brain uptake. We demonstrate that one such conjugate s...
| Main Authors: | , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
American Chemical Society (ACS)
2021
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| Online Access: | https://hdl.handle.net/1721.1/135410 |
| _version_ | 1810987388404498432 |
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| author | Fadzen, Colin M Wolfe, Justin M Zhou, Wen Cho, Choi-Fong von Spreckelsen, Niklas Hutchinson, Kathryn T Lee, Yen-Chun Chiocca, E Antonio Lawler, Sean E Yilmaz, Omer H Lippard, Stephen J Pentelute, Bradley L |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Fadzen, Colin M Wolfe, Justin M Zhou, Wen Cho, Choi-Fong von Spreckelsen, Niklas Hutchinson, Kathryn T Lee, Yen-Chun Chiocca, E Antonio Lawler, Sean E Yilmaz, Omer H Lippard, Stephen J Pentelute, Bradley L |
| author_sort | Fadzen, Colin M |
| collection | MIT |
| description | © 2020 American Chemical Society. Effective delivery to the brain limits the development of novel glioblastoma therapies. Here, we introduce conjugation between platinum(IV) prodrugs of cisplatin and perfluoroaryl peptide macrocycles to increase brain uptake. We demonstrate that one such conjugate shows efficacy against glioma stem-like cells. We investigate the pharmacokinetics of this conjugate in mice and show that the amount of platinum in the brain after treatment with the conjugate is 15-fold greater than with cisplatin after 5 h. |
| first_indexed | 2024-09-23T11:49:19Z |
| format | Article |
| id | mit-1721.1/135410 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:49:19Z |
| publishDate | 2021 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1354102023-11-07T20:08:39Z A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain Fadzen, Colin M Wolfe, Justin M Zhou, Wen Cho, Choi-Fong von Spreckelsen, Niklas Hutchinson, Kathryn T Lee, Yen-Chun Chiocca, E Antonio Lawler, Sean E Yilmaz, Omer H Lippard, Stephen J Pentelute, Bradley L Massachusetts Institute of Technology. Department of Chemistry Koch Institute for Integrative Cancer Research at MIT © 2020 American Chemical Society. Effective delivery to the brain limits the development of novel glioblastoma therapies. Here, we introduce conjugation between platinum(IV) prodrugs of cisplatin and perfluoroaryl peptide macrocycles to increase brain uptake. We demonstrate that one such conjugate shows efficacy against glioma stem-like cells. We investigate the pharmacokinetics of this conjugate in mice and show that the amount of platinum in the brain after treatment with the conjugate is 15-fold greater than with cisplatin after 5 h. 2021-10-27T20:23:21Z 2021-10-27T20:23:21Z 2020 2021-04-27T18:34:39Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135410 en 10.1021/ACS.JMEDCHEM.0C00022 Journal of Medicinal Chemistry Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Fadzen, Colin M Wolfe, Justin M Zhou, Wen Cho, Choi-Fong von Spreckelsen, Niklas Hutchinson, Kathryn T Lee, Yen-Chun Chiocca, E Antonio Lawler, Sean E Yilmaz, Omer H Lippard, Stephen J Pentelute, Bradley L A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain |
| title | A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain |
| title_full | A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain |
| title_fullStr | A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain |
| title_full_unstemmed | A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain |
| title_short | A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain |
| title_sort | platinum iv prodrug perfluoroaryl macrocyclic peptide conjugate enhances platinum uptake in the brain |
| url | https://hdl.handle.net/1721.1/135410 |
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