A thioether-directed palladium-cleavable linker for targeted bioorthogonal drug decaging.
Lopes Bernardes, Goncalo
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Stenton, B. J., Oliveira, B. L., Matos, M. J., Sinatra, L., & Lopes Bernardes, G. (2018). A thioether-directed palladium-cleavable linker for targeted bioorthogonal drug decaging.. Chemical science, 9 (17), 4185-4189. https://doi.org/10.1039/c8sc00256h
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.
Royal Society (uf110046)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (702574)
European Commission Horizon 2020 (H2020) ERC (676832)
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External DOI: https://doi.org/10.1039/c8sc00256h
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277689
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/