The Role of Side Chains in the Fine-Tuning of the Metal-Binding Ability of Multihistidine Peptides.

The systematic studies of copper(II), nickel(II) and zinc(II) ion complexes of protected multihistidine peptides containing amino acids with different side chains (Ac-SarHAH-NH2, Ac-HADH-NH2, Ac-HDAH-NH2, Ac-HXHYH-NH2 X, Y = A, F, D or K, Ac-HXHAHXH-NH2, X = F or D) have provided information about the metal ion and protein interaction and have made it possible to draw conclusions regarding general trends in the coordination of metal complexes of multihistidine peptides. The stability of the metal complexes significantly depends on the position of the histidines and amino acids, which are present in the neighbourhood of the histidine amino acids as well. The most significant effect was observed on peptides containing aspartic acid or phenylalanine. The redox parameters of complexes, however, depend on the number and position of histidines, and the other side chain donor atoms have practically no effect on the electrochemical properties of imidazole-coordinated species. However, the presence of aspartic acid side chains results in a more distorted geometry of amide-coordinated species and increases the reducibility of these complexes.

Coordination, redox properties and SOD activity of Cu(II) complexes of multihistidine peptides.

The results of electrochemical and SOD activity measurements of such copper(II) complexes of terminally protected multihistidine peptides that may mimic the active site of CuZnSOD enzyme are submitted and completed with solution equilibrium studies of some copper(II)-ligand systems. The equilibrium data confirm that the thermodynamic stabilities increase with the increasing number of histidyl residues in the amino acid sequence, the stability order, however, can be finely tuned by the number and quality of amino acids between histidine residues. Based on the cyclic voltammetric studies we concluded that the formal reduction potential values of imidazole nitrogen coordinated complexes decrease with the increasing number of imidazole donor atoms in the coordination sphere. However, the redox parameters of [CuH-1L]+ and [CuH-2L] complexes containing amide nitrogen coordination can be determined as well. All formal potential values of [CuL]2+, [CuH-1L]+ and [CuH-2L] complexes fall in the middle potential range of SOD activity. Finally, after the detailed analysis of species distribution curves based upon the equilibrium data SOD activity of copper(II) containing systems at two pH (pH=6.8 and 7.4) were determined. The imidazole coordinated [CuL]2+ complexes of the multihistidine peptide containing the HXH sequence exhibit the most significant activity, but the presence of amide nitrogen coordinated species with slightly distorted geometry could considerably contribute to the SOD activity.