Highly Specific Oxidative Crosslinking of Proteins Mediated by a Nickel-Peptide Complex

The Ni(II) complex of the tripeptide NH2-Gly-Gly-His-COOH is shown to mediate efficient protein-protein cross-linking in the presence of oxidants such as oxone and monoperoxyphthalic acid. Only proteins that associate specifically in solution are cross-linked under these conditions. Preliminary probes of the mechanism of the reaction suggest that the active intermediate may be a high-valent metal complex that attacks aromatic amino acids.