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 oxi
dants such as oxone and monoperoxyphthalic acid. Only proteins that as
sociate specifically in solution are cross-linked under these conditio
ns. Preliminary probes of the mechanism of the reaction suggest that t
he active intermediate may be a high-valent metal complex that attacks
aromatic amino acids.