Open AccessProtein–Protein Cross-Coupling via Palladium–Protein Oxidative Addition Complexes from Cysteine Residues
Author(s) -
Heemal H. Dhanjee,
Azin Saebi,
Ivan Buslov,
Alexander R. Loftis,
Stephen L. Buchwald,
Bradley L. Pentelute
Publication year - 2020
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.0c03143
Subject(s) - chemistry , cysteine , palladium , covalent bond , oxidative phosphorylation , nucleophile , intramolecular force , combinatorial chemistry , biochemistry , stereochemistry , organic chemistry , catalysis , enzyme
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.