Issue 17, 2018

A thioether-directed palladium-cleavable linker for targeted bioorthogonal drug decaging

Abstract

We describe the development of a bifunctional linker that simultaneously allows site-specific protein modification and palladium-mediated bioorthogonal decaging. This was enabled by a thioether binding motif in the propargyl carbamate linker and a readily available palladium complex. We demonstrate the efficiency of this reaction by controlled drug release from a PEGylated doxorubicin prodrug in cancer cells. The linker can be easily installed into cysteine bearing proteins which we demonstrated for the construction of an anti-HER2 nanobody–drug conjugate. Targeted delivery of the nanobody drug conjugate showed effective cell killing in HER2+ cells upon palladium-mediated decaging.

Graphical abstract: A thioether-directed palladium-cleavable linker for targeted bioorthogonal drug decaging

Supplementary files

Article information

Article type
Edge Article
Submitted
16 janv. 2018
Accepted
02 avr. 2018
First published
06 avr. 2018
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2018,9, 4185-4189

A thioether-directed palladium-cleavable linker for targeted bioorthogonal drug decaging

B. J. Stenton, B. L. Oliveira, M. J. Matos, L. Sinatra and G. J. L. Bernardes, Chem. Sci., 2018, 9, 4185 DOI: 10.1039/C8SC00256H

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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