Journal
CHEMICAL SCIENCE
Volume 9, Issue 17, Pages 4185-4189Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c8sc00256h
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Funding
- EPSRC
- European Commission (Marie-Skoldowska Curie fellowship)
- Xunta de Galicia (Postdoctoral fellowship)
- FCT Portugal (iFCT)
- EPSRC [EP/M003647/1] Funding Source: UKRI
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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.
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