A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain
The Pentelute Lab aims to invent new chemistry for the efficient and selective modification of proteins, to ‘hijack’ these biological machines for efficient drug delivery into cells and to create new machines to rapidly and efficiently manufacture peptides and proteins.
Pentelute Lab, Chemistry, MIT, Chemistry Department, Boston, Cambridge, Biology, Peptides, Peptide, Proteins, Science, Rapid, Brad Pentelute, Brad,
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A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain

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

J. Med. Chem. 2020, 63, 13, 6741–6747
Publication Date:May 15, 2020
https://doi.org/10.1021/acs.jmedchem.0c00022


Colin M. FadzenColin 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*, and Bradley L. Pentelute

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.

Category
2020, Publications