Potentiometric and NMR studies on Cd2+ coordination with the histidine-containing Ac184–188NH2 prion protein fragment

To elucidate the specific mode and site of binding between metal ions and prion protein (PrPc), we synthesized the pentapeptide Ac184–188NH2 (AcIKQHTNH2), corresponding to helical region II of the protein, and its analogous acetylated at the lysine side chain. The acid–base properties of both peptides and their interaction with Cd2+ were studied in aqueous solution by NMR and potentiometry. Speciation data were compared with those achieved for Cd2+/4-methylimidazole, taken as the reference system. Both NMR and potentiometric data indicate that Cd2+ is coordinated by the histidine residue. The involvement of the side chain amine of lysine in the metal coordination is excluded by NMR data, whereas a role for either the carbonyl or the amide group of threonine is suggested.

Graphical abstractThe coordination behavior of the model pentapeptide AcIKQHTNH2 with Cd(II) in H2O is studied by potentiometry and NMR. The metal coordinates histidine selectively.Figure optionsDownload full-size imageDownload as PowerPoint slide