Competition of zinc(II) with cadmium(II) or mercury(II) in binding to a 12-mer peptide

• The peptide Ac-SCPGDQGSDCSI-NH2 binds Zn2 + with a remarkably high affinity.
• We propose two Cys-thiolates and one Asp-carboxylate to bind Zn2 + in the ZnL complex.
• One equiv. of Hg2 + fully replaces Zn2 + from its ZnL complex.
• One equiv. of Cd2 + partially replaces Zn2 + and mixed metal complexes may also form.

Speciation of the complexes of zinc(II) with a dodecapeptide (Ac-SCPGDQGSDCSI-NH2), inspired by the metal binding domain of MerR metalloregulatory proteins, have been studied by pH-potentiometric titrations, UV, SRCD (synchrotron radiation circular dichroism) and 1H NMR experiments. (MerR is a family of transcriptional regulators the archetype of which is the Hg2 +-responsive transcriptional repressor-activator MerR protein.) The aim of the ligand-design was to retain the advantageous metal binding features of MerR proteins in a model peptide for the efficient capture of toxic metal ions. The peptide binds zinc(II) via two deprotonated Cys-thiol groups and one of the Asp-carboxylates in the ZnL parent complex, possessing a remarkably high stability (logK = 9.93). In spite of the relatively long peptide loop, bis-complexes are also formed with the metal ion under basic conditions. In a competition with cadmium(II) or mercury(II), zinc(II) cannot prevent the binding of toxic metal ions by the thiolate donor groups of the ligand. Around neutral pH one equivalent of mercury(II) was shown to fully replace zinc(II) from the ZnL species. Partial replacement of zinc(II) from the peptide by one equivalent of cadmium(II), relative to zinc(II) and the ligand, is also presumable, nevertheless, spectroscopic data may suggest the formation of mixed metal ion complexes, as well. Based on the obtained results the investigated dodecapeptide can be a promising candidate for capturing toxic metal ions in practical applications.

Interaction of Zn2 + with the Ac-SCPGDQGSDCSI-NH2 peptide, and competition with Cd2 + and Hg2 + in binding to the ligand have been investigated.Figure optionsDownload as PowerPoint slide