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-NH2 and Ac-HVGDH-NH2) 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 beta-carboxylate groups of FDAH and VIDAH create a very effective metal binding site with the (NH2, N-, beta-COO-) and (NH2, N-, N-, beta- COO-) coordination modes including the N- termini, while the histidine sites are available for the formation of the (N-im, N-, N-) binding mode resulting in the preference of dinuclear complex formation. Copyright (c) 2007.