A Platinum(IV) Prodrug - Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain

Colin M. Fadzen; Justin M. Wolfe; Wen Zhou; Choi Fong Cho; Niklas Von Spreckelsen; Kathryn T. Hutchinson; Yen Chun Lee; E. Antonio Chiocca; Sean E. Lawler; Omer H. Yilmaz; Stephen J. Lippard; Bradley L. Pentelute

doi:10.1021/acs.jmedchem.0c00022

A Platinum(IV) Prodrug - Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain

Colin M. Fadzen
, Justin M. Wolfe
, Wen Zhou
, Choi Fong Cho
, Niklas Von Spreckelsen
, Kathryn T. Hutchinson
, Yen Chun Lee
, E. Antonio Chiocca
, Sean E. Lawler
, Omer H. Yilmaz
, Stephen J. Lippard
, Bradley L. Pentelute

化學系

研究成果: Article › 同行評審

33 引文斯高帕斯（Scopus）

摘要

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.

原文	English
頁（從 - 到）	6741-6747
頁數	7
期刊	Journal of Medicinal Chemistry
卷	63
發行號	13
DOIs	https://doi.org/10.1021/acs.jmedchem.0c00022
出版狀態	Published - 2020 7月 9

All Science Journal Classification (ASJC) codes

分子醫學
藥物發現

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10.1021/acs.jmedchem.0c00022

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Fadzen, C. M., Wolfe, J. M., Zhou, W., Cho, C. F., Von Spreckelsen, N., Hutchinson, K. T., Lee, Y. C., Chiocca, E. A., Lawler, S. E., Yilmaz, O. H., Lippard, S. J., & Pentelute, B. L. (2020). A Platinum(IV) Prodrug - Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain. Journal of Medicinal Chemistry, 63(13), 6741-6747. https://doi.org/10.1021/acs.jmedchem.0c00022

@article{99a75cb759024c5cbdd4f53787f552e7,

title = "A Platinum(IV) Prodrug - Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain",

abstract = "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.",

author = "Fadzen, \{Colin M.\} and Wolfe, \{Justin M.\} and Wen Zhou and Cho, \{Choi Fong\} and \{Von Spreckelsen\}, Niklas and Hutchinson, \{Kathryn T.\} and Lee, \{Yen Chun\} and Chiocca, \{E. Antonio\} and Lawler, \{Sean E.\} and Yilmaz, \{Omer H.\} and Lippard, \{Stephen J.\} and Pentelute, \{Bradley L.\}",

note = "Publisher Copyright: {\textcopyright} 2020 American Chemical Society.",

year = "2020",

month = jul,

day = "9",

doi = "10.1021/acs.jmedchem.0c00022",

language = "English",

volume = "63",

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journal = "Journal of Medicinal Chemistry",

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Fadzen, CM, Wolfe, JM, Zhou, W, Cho, CF, Von Spreckelsen, N, Hutchinson, KT, Lee, YC, Chiocca, EA, Lawler, SE, Yilmaz, OH, Lippard, SJ & Pentelute, BL 2020, 'A Platinum(IV) Prodrug - Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain', Journal of Medicinal Chemistry, 卷 63, 編號 13, 頁 6741-6747. https://doi.org/10.1021/acs.jmedchem.0c00022

TY - JOUR

T1 - A Platinum(IV) Prodrug - Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain

AU - Fadzen, Colin M.

AU - Wolfe, Justin M.

AU - Zhou, Wen

AU - Cho, Choi Fong

AU - Von Spreckelsen, Niklas

AU - Hutchinson, Kathryn T.

AU - Lee, Yen Chun

AU - Chiocca, E. Antonio

AU - Lawler, Sean E.

AU - Yilmaz, Omer H.

AU - Lippard, Stephen J.

AU - Pentelute, Bradley L.

PY - 2020/7/9

Y1 - 2020/7/9

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85088210962

UR - https://www.scopus.com/pages/publications/85088210962#tab=citedBy

U2 - 10.1021/acs.jmedchem.0c00022

DO - 10.1021/acs.jmedchem.0c00022

M3 - Article

C2 - 32410451

AN - SCOPUS:85088210962

SN - 0022-2623

VL - 63

SP - 6741

EP - 6747

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 13

ER -

A Platinum(IV) Prodrug - Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain

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