Complex Formation and Hydrolytic Processes of Protected Peptides Containing the -SXH- Motif in the Presence of...

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-NH₂, A₃SSH-NH₂, A₄SSH-NH₂, AAAϵKSH-NH₂. The Ni(II)-induced hydrolysis of Ac-SKHM-NH₂ 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 [Ni₂LH_-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 A₄SSH-NH₂, both Ni(II) ions fulfill the conditions for hydrolysis, which was confirmed by HPLC analyses at pH ≈8.2 and 25 °C.