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

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

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.

Original language	English
Pages (from-to)	6741-6747
Number of pages	7
Journal	Journal of Medicinal Chemistry
Volume	63
Issue number	13
DOIs	https://doi.org/10.1021/acs.jmedchem.0c00022
Publication status	Published - 2020 Jul 9

All Science Journal Classification (ASJC) codes

Molecular Medicine
Drug Discovery

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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

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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.}",

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

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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, vol. 63, no. 13, pp. 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.

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SN - 0022-2623

VL - 63

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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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All Science Journal Classification (ASJC) codes

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