Potentiometric and NMR studies on Cd 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 (PrP^c), 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.