PMID- 32364380 OWN - NLM STAT- MEDLINE DCOM- 20210416 LR - 20210521 IS - 1520-5126 (Electronic) IS - 0002-7863 (Print) IS - 0002-7863 (Linking) VI - 142 IP - 20 DP - 2020 May 20 TI - Protein-Protein Cross-Coupling via Palladium-Protein Oxidative Addition Complexes from Cysteine Residues. PG - 9124-9129 LID - 10.1021/jacs.0c03143 [doi] AB - 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. FAU - Dhanjee, Heemal H AU - Dhanjee HH AUID- ORCID: 0000-0002-3532-4430 AD - Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States. FAU - Saebi, Azin AU - Saebi A AD - Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States. FAU - Buslov, Ivan AU - Buslov I AD - Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States. FAU - Loftis, Alexander R AU - Loftis AR AD - Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States. FAU - Buchwald, Stephen L AU - Buchwald SL AUID- ORCID: 0000-0003-3875-4775 AD - Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States. FAU - Pentelute, Bradley L AU - Pentelute BL AUID- ORCID: 0000-0002-7242-801X AD - Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States. LA - eng GR - F32 GM131592/GM/NIGMS NIH HHS/United States GR - P30 ES002109/ES/NIEHS NIH HHS/United States GR - R01 GM110535/GM/NIGMS NIH HHS/United States GR - U54 AI057159/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200511 PL - United States TA - J Am Chem Soc JT - Journal of the American Chemical Society JID - 7503056 RN - 0 (Organometallic Compounds) RN - 0 (Proteins) RN - 5TWQ1V240M (Palladium) RN - K848JZ4886 (Cysteine) SB - IM EIN - J Am Chem Soc. 2020 Jul 15;142(28):12548. PMID: 32603593 MH - Cysteine/*chemistry MH - Models, Molecular MH - Molecular Structure MH - Organometallic Compounds/*chemistry MH - Oxidation-Reduction MH - Palladium/*chemistry MH - Protein Binding MH - Proteins/*chemistry PMC - PMC7586714 MID - NIHMS1633230 EDAT- 2020/05/05 06:00 MHDA- 2021/04/17 06:00 PMCR- 2021/05/20 CRDT- 2020/05/05 06:00 PHST- 2020/05/05 06:00 [pubmed] PHST- 2021/04/17 06:00 [medline] PHST- 2020/05/05 06:00 [entrez] PHST- 2021/05/20 00:00 [pmc-release] AID - 10.1021/jacs.0c03143 [doi] PST - ppublish SO - J Am Chem Soc. 2020 May 20;142(20):9124-9129. doi: 10.1021/jacs.0c03143. Epub 2020 May 11.