Palladium Oxidative Addition Complexes for Peptide and Protein Cross-linking
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nihms940702.pdf
Description
Accepted version
Size
1.28 MB
Format
Adobe PDF
Checksum (MD5)
61685b8edea079228a365df568655345
Author(s)
Kubota, Koji
Dai, Peng
Pentelute, Bradley L.
Buchwald, Stephen Leffler
Date Issued
February 2018
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Kubota, Koji, et al. "Palladium Oxidative Addition Complexes for Peptide and Protein Cross-linking." Journal of the American Chemical Society 140, 8 (Feb. 2018): p. 3128-33 doi 10.1021/JACS.8B00172 ©2018 Author(s)
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1021/JACS.8B00172
