Work

Palladium Oxidative Addition Complexes for Peptide and Protein Cross-linking

Year: 2018

Type: article

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.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.8b00172

Authors: Koji Kubota, Peng Dai, Bradley L. Pentelute, Stephen L. Buchwald

Institution: Massachusetts Institute of Technology

Language: English

Topic: Biochemical and Structural Characterization

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Ministry of Education, Culture, Sports, Science and Technology, National Institutes of Health, Japan Society for the Promotion of Science, National Institute of General Medical Sciences

Awards: Cysteine Arylation, Catalytic Methods for Organic Synthesis, Metal-Catalyzed Methods for Organic Synthesis