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Updated: Feb 10, 2026

Single-step Purification of Macromolecular Complexes Using RNA Attached to Biotin and a Photo-cleavable Linker
Published on: January 3, 2019
A thioether-directed palladium-cleavable linker for targeted bioorthogonal drug decaging
Benjamin J Stenton1, Bruno L Oliveira1, Maria J Matos1
1Department of Chemistry , University of Cambridge , Lensfield Road , CB2 1EW Cambridge , UK .
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.
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