Abstract
Synergistic effects and promising anticancer activities encourage the combination of non-steroidal anti-inflammatory drugs with metallodrugs. Here, we discuss the interactions of an organometallic complex consisting of an acetylsalicylic acid (ASA) moiety attached to a PtII center via an alkenol linker in a Zeise's salt-type coordination (ASA-buten-PtCl3) with model peptides angiotensin 1 (AT), substance P (Sub P), and ubiquitin (UQ). Top-down mass spectrometry experiments show that the amino acid involved in the initial binding to the metal complex controls the coordination sphere of PtII in the adducts. The strong trans labilizing effect of the coordinating sulfur atom in Met causes fast release of the organic moiety and leads to the formation of dimers and oligomers in the case of Sub P. In contrast, interactions with nitrogen donors in AT result in stable adducts containing the intact ASA-buten-PtII complex. UQ forms two sets of PtII adducts, only one of them retains the ASA moiety, which is presumably the result of an unexpected binding geometry. Importantly, UQ is additionally acetylated at various Ser and Lys residues by the ASA-buten-PtCl3 complex. Control experiments with ASA are negative. This is the first example of concomitant platination and acetylation of a peptide with an ASA metal complex.