Complex Formation and Hydrolytic Processes of Protected Peptides Containing the –SXH– Motif in the Presence of Nickel(II) Ion

Abstract Interactions between metal ions and proteins are considered reversible, such as the coordination of a metal ion to a protein or enzyme, but irreversible processes like the oxidative reactions, aggregation or hydrolytic processes may occur. In the presence of Ni(II)‐ions selective hydrolysis of the peptides containing the −SXH− or −TXH− motif was observed. Since the side chain of histidine serves as the metal ion binding site for many native proteins, and very often histidine is present in a −SXH− or −TXH− sequence, to study the complex formation and hydrolytic processes in presence of nickel(II) ion four peptides were synthesised: Ac‐SKHM‐NH 2 , A 3 SSH‐NH 2 , A 4 SSH‐NH 2 , AAAϵKSH‐NH 2 . The Ni(II)‐induced hydrolysis of Ac‐SKHM‐NH 2 peptide occurs rapidly in alkaline medium already at room temperature. In two peptides containing −SSH− sequence on the C‐termini, the N‐terminal part is the major binding site for the nickel(II) ion, but the formation of dinuclear complexes was also observed. In the [Ni 2 LH −6 ] 2− complex of hexapeptide, the coordination sphere of the metal ions is saturated with deprotonated Ser‐O − , which does not result in hydrolysis of the peptide. For A 4 SSH‐NH 2 , both Ni(II) ions fulfill the conditions for hydrolysis, which was confirmed by HPLC analyses at pH ≈8.2 and 25 °C.