Short oligopeptides with three cysteine residues as models of sulphur-rich Cu(i)- and Hg(ii)-binding sites in proteins

• Published in: Metallomics 2018-09, Vol.10 (9), p.1232-1244
• Main Authors: Mesterházy, Edit, Lebrun, Colette, Crouzy, Serge, Jancsó, Attila, Delangle, Pascale
• Format: Article
• Language: English
• Subjects: Binding sites; Biochemistry, Molecular Biology; Chemical Sciences; Copper; Cysteine; Inorganic chemistry; Life Sciences; Mercury; Mercury compounds; Metal concentrations; Metal ions; Metallothioneins; Oligopeptides; Peptides; pH effects; Proteins; Sulfur
• ISSN: 1756-5901; 1756-591X
• DOI: 10.1039/c8mt00113h

The essential Cu(i) and the toxic Hg(ii) ions possess similar coordination properties, and therefore, similar cysteine rich proteins participate in the control of their intracellular concentration. In this work we present the metal binding properties of linear and cyclic model peptides incorporating the three-cysteine motifs, CxCxxC or CxCxC, found in metallothioneins. Cu(i) binding to the series of peptides at physiological pH revealed to be rather complicated, with the formation of mixtures of polymetallic species. In contrast, the Hg(ii) complexes display well-defined structures with spectroscopic features characteristic for a HgS2 and HgS3 coordination mode at pH = 2.0 and 7.4, respectively. Stability data reflect a ca. 20 orders of magnitude larger affinity of the peptides for Hg(ii) (log βpH7.4HgP ≈ 41) than for Cu(i) (log βpH7.4CuP ≈ 18). The different behaviour with the two metal ions demonstrates that the use of Hg(ii) as a probe for Cu(i), coordinated by thiolate ligands in water, may not always be fully appropriate.