Thermodynamic and Structural Characterization of the Copper(II) Complexes of Peptides Containing Both Histidyl and Aspartyl Residues

Terminally protected pentapeptides with 2 histidines (Ac-HHVGD- [Formula: see text] and Ac-HVGDH- [Formula: see text]) and the terminally free peptides containing both internal aspartyl and C-terminal histidyl residues (FDAH and VIDAH) have been synthesized, and copper(II) complexes studied by potentiometric, UV-Vis, CD, and EPR spectroscopic techniques in solution. Both thermodynamic and spectroscopic data reveal that side chain donor atoms of aspartyl and histidyl residues have a significant contribution to the metal binding affinity of peptide molecules. In the case of terminally protected peptides, the role of the imidazole-N donor functions is reflected in the enhanced stability of the 3N and 4N coordinated copper(II) complexes. The amino and [Formula: see text]-carboxylate groups of FDAH and VIDAH create a very effective metal binding site with the ([Formula: see text] , [Formula: see text] , [Formula: see text]) and ([Formula: see text] , [Formula: see text] , [Formula: see text] , [Formula: see text]) coordination modes including the N-termini, while the histidine sites are available for the formation of the ([Formula: see text] , [Formula: see text] , [Formula: see text]) binding mode resulting in the preference of dinuclear complex formation.