Use of heavy-metal clusters in the design of N-succinimidyl eater acylation reagents for side-chain-specific labeling of proteins

New heavy transition metal carbonyl markers for protein labeling, containin g an "M-n(CO)(11)" (M = Ru, Os, n = 3; M = Ir, n = 4) moiety, were prepared by reaction of "lightly stabilized" clusters with an N-succinimidyl ester functionalized phosphine, namely N-succinimidyl 3-diphenylphosphine-propion ate (DPPS). The reaction of Os-3(CO)(11)(DPPS) with the model amino acid be ta-alanine was performed and led to the expected amide. From the reaction o f M-n(CO)11(DPPS) with bovine serum albumin (BSA) in mixed organic/aqueous medium, conjugates bearing a fairly high number of metal carbonyl fragments were obtained, thus demonstrating the usefulness of this class of reagents for the selective and covalent graft of heavy metal clusters to side chain of proteins.