Protein–Protein Cross-Coupling via Palladium–Protein Oxidative Addition Complexes from Cysteine Residues
- 11 May 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 142 (20), 9124-9129
- https://doi.org/10.1021/jacs.0c03143
Abstract
Few chemical methods exist for the covalent conjugation of two proteins. We report the preparation of site-specific protein-protein conjugates that arise from the sequential cross-coupling of cysteine residues on two different proteins. The method involves the synthesis of stable palladium-protein oxidative addition complexes (Pd-protein OACs), a process that converts nucleophilic cysteine residues into an electrophilic S-aryl-Pd-X unit by taking advantage of an intramolecular oxidative addition strategy. This process is demonstrated on proteins up to 83 kDa in size and can be conveniently carried out in water and open to air. The resulting Pd-protein OACs can cross-couple with other thiol-containing proteins to arrive at homogeneous protein-protein bioconjugates.Keywords
Funding Information
- U.S. Department of Health and Human Services (P30-ES002109)
- Schweizerischer Nationalfonds zur F??rderung der Wissenschaftlichen Forschung (Early Post-doctoral Mobility Fellowship)
- U.S. Department of Health and Human Services (1F32GM131592-01A1, R01 GM110535)
- National Science Foundation (1122374)
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