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Issue 17, 2018
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A thioether-directed palladium-cleavable linker for targeted bioorthogonal drug decaging

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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

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Publication details

The article was received on 16 Jan 2018, accepted on 02 Apr 2018 and first published on 06 Apr 2018


Article type: Edge Article
DOI: 10.1039/C8SC00256H
Citation: Chem. Sci., 2018,9, 4185-4189
  • Open access: Creative Commons BY license
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    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

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