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Palladium Oxidative Addition Complexes for Peptide and Protein Cross-linking.

ABSTRACT: A new method for cysteine-lysine cross-linking in peptides and proteins using palladium oxidative addition complexes is presented. First, a biarylphosphine-supported palladium reagent is used to transfer an aryl group bearing an O-phenyl carbamate substituent to a cysteine residue. Next, this carbamate undergoes chemoselective acyl substitution by a proximal lysine to form a cross-link. The linkage so formed is stable toward acid, base, oxygen, and external thiol nucleophiles. This method was applied to cross-link cysteine with nearby lysines in sortase A*. Furthermore, we used this method for the intermolecular cross-linking between a peptide and a protein based on the p53-MDM2 interaction. These studies demonstrate the potential for palladium-mediated methods to serve as a platform for the development of future cross-linking techniques for peptides and proteins with natural amino acid residues.

SUBMITTER: Kubota K

PROVIDER: S-EPMC5831526 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Palladium Oxidative Addition Complexes for Peptide and Protein Cross-linking.

Kubota Koji K Dai Peng P Pentelute Bradley L BL Buchwald Stephen L SL

Journal of the American Chemical Society 20180213 8

A new method for cysteine-lysine cross-linking in peptides and proteins using palladium oxidative addition complexes is presented. First, a biarylphosphine-supported palladium reagent is used to transfer an aryl group bearing an O-phenyl carbamate substituent to a cysteine residue. Next, this carbamate undergoes chemoselective acyl substitution by a proximal lysine to form a cross-link. The linkage so formed is stable toward acid, base, oxygen, and external thiol nucleophiles. This method was ap ...[more]

PMID: 29406701

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